Frequesntly Asked Questions (FAQs)
QUESTIONS
Q.1 Is EURAMOS 1 included in the National Research Register?Q.2 Is the Investigator Statement the same as the Form of Participation?
Q.3 Does submission to Ethics have to be done separately for paediatric and adult units?
Q.4 If two centres have the same PI do they have to fill out two investigator statements?
Q.5 Do the local pathologists and surgeons need to sign the Delegation Log?
Q.6 Is there a specific form for drug accountability
Q.7 If one data manager works at 2 sites, do 2 complete site files need to be kept and maintained separately?
Q.8 Since bone scans are one of the essential investigations in EURAMOS 1 protocol, will an ARSAC (Administration of Radioactive Substances Advisory Committee) licence need to be applied for?
Q.9 When is the next Investigators’ Meeting?
Q.10 If a data manager fills in part of an SAE form i.e. name, D.O.B etc, do they need to indicate this on the delegation log?
Q.11 Can completed CRFs be kept in the patient notes and referenced to the site file?
Q.12 Are patient diary cards compulsory?
Q.13 On the consent forms, who is the Researcher?
Q.14 Can research nurses consent patients for EURAMOS 1 or can only the clinicians do this?
Q.15 What is the procedure for registering new patients?
Q.16 Is it possible to register patients after chemotherapy treatment has started?
Q.17 When registering a patient, if there is some question about the possibility that the patient has lung metastases, should we hold on to the registration form until this has been confirmed or should we return the form straight away?
Q.18 What is the procedure for randomising patients?
Q.19 What is the procedure if a registered patient is not to be randomised?
Q.20 Can a patient be randomised using the local pathologist's assessment of the histological response?
Q.21 If a patient was not randomised but later went on to have thoracotomy, does a Thoracotomy form need to be completed?
Q.22 If a patient did not fill out the first Quality of Life questionnaire at week 5 of the protocol, is it still relevant to ask for further questionnaires to be completed?
Q.23 For patients who have consented to participate in the parallel Biological Study, when should blood samples be collected, how should the samples be stored and when will they be collected?
Q.24 When a patient is randomised to MAPifn, what is the procedure for requesting PegIntron supply?
Q.25 Is GCSF being supplied free of charge?
Q.26 Who is the contact at Chugai Pharma UK?
Q.27 At the end of their first session of Cisplatin and Doxorubicin, the patient was still suffering from nausea and vomiting and so was kept in hospital overnight and was discharged the following day. Should this be reported as a SAE?
Q.28 Is it acceptable if imaging takes place in more than one site?
Q.29 Do we need to confirm bone scan or plain radiograph suspected metastases on MR / biopsy?
Q.30 Should patients on EURAMOS 1 be given Septrin or anti-fungal prophylaxis?
Q.31 Could doxorubicin been administered as a daily bolus at the time point 1, 24, 48 hours instead of the 48-hour continuous infusion stated in the protocol?
Q.32 Is it possible to continue on trial without using dexrazoxane if left ventricular ejection fraction falls?
Q.33 Is carboxypeptidase mandatory in the case of delayed methotrexate elimination or methotrexate-related renal toxicity?
Q.34 Could different folinic acid rescue regimen be used than the one stated in the protocol?
Q.35 “Urinary electrolyte wasting” is one of the adverse events mentioned on the chemotherapy form. What does it refer to?
Q.36 How frequently should Glomerular Filtration Rate (GFR) be measured directly by radionuclide determination?
Q.37 Can the dose of Peg interferon can be rounded up or down to the nearest dose
Q.38 If a patient does not complete their 2 cycles of chemo before surgery are they ineligible for randomisation?
Q.39 On page 24 of the protocol 8.2.4, recommended baseline assessment of organ function, asks for an ECHO. However, this is not included in 8.3.4, after last cycle of chemotherapy. 8.4.2 Toxicity/Late Effects Related Follow Up includes ECHO as one of the investigations that is required to be performed annually. Is it an omission from 8.3.4, should an ECHO be included in the investigations required after the last cycle of chemotherapy?
Q.40 Should neutropenic sepsis be reported as an SAE?
Q.41 What is the definition of progressice disease?
Q.42 If a patient does not complete their 2 cycles of chemo before surgery are they ineligible for randomisation?
Q.43 Can the dose of Peg interferon be rounded up or down to the nearest dose?
Q.44 How should blood samples for the biological studies be stored?
Q.45 Methotrexate dose: should it be capped in patients with surface area >2 m2?
Q.46 How often should heart function be checked?
Q.47 Patient started interferon in March ’07. At the end of December 2007 the patient decided for social reasons to discontinue treatment with interferon. In May 2008 the patient requested to restart interferon and continue with the trial. Is this possible?
Q.48 We have a patient on EURAMOS 1 who should be having surgery this week but not sure if this is going to go ahead. Should we be giving additional methotrexate if surgery is delayed?
Q.49 Should a patient who developed acute renal failure induced by high dose methotrexate and required glucarpidase rescue be re-challenged with methotrexate assuming good full renal recovery?
Q.50 Is audiometry assessment at baseline essential?
Q.51 What tests should be done for the urine phosphate and creatinine assessment?
Q.52 Interferon alfa-2b and Male Fertility
Q.53 Could we perform a PET scan instead of bone scan for staging? Would that be acceptable to you?
Q.54 Do we collect CRFs for patients who refuse randomization? I thought that we do. What about QOL forms?
Q.55 I am arranging follow up for patient who is on the euramos trial. I notice that an Echo cardiogram and hearing test need doing every 12 months. However, this does not coincide with out patient appointment by a few months. Can I do scans to correspond with outpatients appointment and gradually bring them into line?
ANSWERS
Q.1 Is EURAMOS 1 included in the National Research Register?Yes
Q.2 Is the Investigator Statement the same as the Form of Participation?
Yes
Q.3 Does submission to Ethics have to be done separately for paediatric and adult units?
No, as long as they are on the same site and under the supervision of the same PI
Q.4 If two centres have the same PI do they have to fill out two investigator statements?
No, as long as the investigator statement makes it clear that it is for two centres
Q.5 Do the local pathologists and surgeons need to sign the Delegation Log?
No, as their involvement in the trial is no different to how they would normally treat the patient.
However, if they fill in any of the CRFs, such as pathology or surgery forms, they should sign the delegation log.
Q.6 Is there a specific form for drug accountability
No, drug accountability can take place as per normal local practice
Q.7 If one data manager works at 2 sites, do 2 complete site files need to be kept and maintained separately?
Either one or two site files can be maintained, as long as the data manager is able to retrieve all documents related to each site
Q.8 Since bone scans are one of the essential investigations in EURAMOS 1 protocol, will an ARSAC (Administration of Radioactive Substances Advisory Committee) licence need to be applied for?
This is a local decision based on standard local care.
However, for EURAMOS 1 we would not expect the centre to need to apply for a ARSAC license because the scans required are part of the standard routine clinical care for osteosarcoma patients.
Q.9 When is the next Investigators’ Meeting?
Investigators' meetings have previously taken place in London (June 2005), Glasgow (April 2006), Oslo, Norway (October, 2006) and most recently in Surrey (Jan 2008).
The next Investigators' meeting has not yet been confirmed.
Q.10 If a data manager fills in part of an SAE form i.e. name, D.O.B etc, do they need to indicate this on the delegation log?
No, as they will not be signing the form
Q.11 Can completed CRFs be kept in the patient notes and referenced to the site file?
Yes
Q.12 Are patient diary cards compulsory?
No
Q.13 On the consent forms, who is the Researcher?
Researcher refers to the Investigator.
The Consent form should be signed by an Investigator - that is any of the clinicians that have signed the Delegation of Responsibilities Log
Q.14 Can research nurses consent patients for EURAMOS 1 or can only the clinicians do this?
Research nurses can obtain the patients consent, but the Investigator must also sign the Consent form.
Q.15 What is the procedure for registering new patients?
To register a patient, please complete the registration form (form 1) before calling the MRC CTU registration/randomisation line on +44(0)207 670 4777.
Provided that the patient is eligible an identification number will be assigned.
The completed registration form should be returned to the MRC CTU within 7 days of registering the patient.
Q.16 Is it possible to register patients after chemotherapy treatment has started?
Patients must be registered within 30 days of diagnostic biopsy and before chemotherapy has taken place.
Please note that patients can be registered on the same day as the first cycle of chemotherapy begins.
Q.17 When registering a patient, if there is some question about the possibility that the patient has lung metastases, should we hold on to the registration form until this has been confirmed or should we return the form straight away?
Question 13 on the Registration form (form 1) should be answered '2' i.e. 'possible lung metastases' and the form returned immediately to the MRC Clinical Trials Unit.
Whether or not the patient had any lung metastases can be confirmed at the time of randomisation on the Randomisation Checklist (form 2), question 9.
Q.18 What is the procedure for randomising patients?
The patient’s histological response must be confirmed (by the review pathologist where possible) and the patient randomised within 35 days after definitive surgery.
The surgery form must be completed and returned to the MRC CTU before randomisation takes place, along with all pre-operative chemotherapy forms.
To randomise a patient, please complete all sections of the randomisation checklist (form 2) before calling the MRC CTU registration/randomisation line on +44 (0)207 670 4777.
Provided that the patient is eligible a treatment will be assigned. The completed randomisation form should be returned to the MRC CTU within 7 days of randomising the patient.
Q.19 What is the procedure if a registered patient is not to be randomised?
For patients who are not to be randomised, please complete the randomisation checklist (form 2) answering 'No' to question 12 and return the form to the MRC Clinical Trials Unit as soon as possible.
Q.20 Can a patient be randomised using the local pathologist's assessment of the histological response?
Where possible, please use the review pathologist's assessment.
However, if the review pathologist's assessment is not available within 35 days of surgery then the local pathologist's assessment can be used.
If you have not received confirmation of the patients histological response from the review pathologist, please contact the review pathologist prior to randomisation to check whether the assessment is available.
Q.21 If a patient was not randomised but later went on to have thoracotomy, does a Thoracotomy form need to be completed?
No, you do not need to complete the Thoracotomy form (form 9) for patients who are not randomised but later have thoracotomy.
Q.22 If a patient did not fill out the first Quality of Life questionnaire at week 5 of the protocol, is it still relevant to ask for further questionnaires to be completed?
The first questionnaire is not a true baseline questionnaire as it is completed after treatment begins therefore it is likely that the questionnaires will be used to look at how each patient was feeling at each individual time point rather than comparing across the time points.
Therefore, we should continue to collect as many questionnaires as possible regardless of whether the week 5 questionnaire was completed.
Q.23 For patients who have consented to participate in the parallel Biological Study, when should blood samples be collected, how should the samples be stored and when will they be collected?
A 10ml EDTA blood sample should be taken from the patient, BEFORE treatment begins.
DNA will be collected from the blood and so samples should be stored to allow for this, as per local practice.
It is not yet certain when the blood samples will be required and so samples should be stored until further notice.
Q.24 When a patient is randomised to MAPifn, what is the procedure for requesting PegIntron supply?
When a patient is randomised to MapInfo, the MRC CTU will automatically request the first three months of PegIntron supply for that patient from Schering Plough, which will be delivered to the hospital Pharmacy. A copy of the PegIntron request form will be forwarded to the hospital Pharmacist as confirmation that the drug has been ordered. It is then the responsibility of the hospital pharmacist to request subsequent PegIntron supply for that patient directly from Schering Plough. Guidelines on how to order subsequent supplies will be sent to the pharmacist and are also available on the EURAMOS website. The 'Drug Re-Request form' is available on the EURAMOS website (Participating Institutions/Pharmacy).
Q.25 Is GCSF being supplied free of charge?
The use of G-CSF (Human Granulocyte Colony Stimulating Factor) is recommended when chemotherapy induced myelosuppression leads to treatment delays.
There will be a 25% retrospective stock reimbursement for GranocyteTM (rHuG-CSF, lenogastrim) used within this study for patients treated within the protocol in the UK.
In the UK, Granocyte is manufactured by Chugai Pharma UK Limited and distributed by Aventis UK ( Tel. 07774 415571, Fax 0208 9875661).
For reimbursement, please complete a reimbursement form, available on the EURAMOS website (Participating Institutions/Pharmacy).
Q.26 Who is the contact at Chugai Pharma UK?
Mr David Eves: Tel. +44 (0)7774415571, email d.eves@chugai-pharm.co.uk
Q.27 At the end of their first session of Cisplatin and Doxorubicin, the patient was still suffering from nausea and vomiting and so was kept in hospital overnight and was discharged the following day. Should this be reported as a SAE?
This is defined as a SAE as it required hospitalization or prolongation of an existing hospitalization, however the EURAMOS 1 protocol (section 13.4) has defined some exceptions for SAE reporting: Hospitalisation for chemotherapy is not reported as an SAE.
In addition expected side effects of chemotherapy, which are listed in the product information, will not be reported on an SAE form for the purposes of this clinical trial unless in the opinion of the investigator they unexpectedly prolonged the hospitalization or required intensive care therapy.
Q.28 Is it acceptable if imaging takes place in more than one site?
Yes it is. However, reports of imaging should be kept in the patient’s notes
Q.29 Do we need to confirm bone scan or plain radiograph suspected metastases on MR / biopsy?
We would certainly recommend confirmation of suspected bone metastases either by MRI or biopsy as this has such a fundamental impact on treatment and prognosis.
This is referring to cases where one may see one or two suspected lesions on bone scan.
Q.30 Should patients on EURAMOS 1 be given Septrin or anti-fungal prophylaxis?
Concurrent use of methotrexate and Septrin (co-trimoxazole) decreases the renal excretion of Methotrexate. This may prolong the need for intravenous hydration, folinic acid rescue and hospitalisation and lead to increased methotrexate toxicity. Therefore Septrin should not be used. There is no need for anti-fungal prophylaxis.
Q.31 Could doxorubicin been administered as a daily bolus at the time point 1, 24, 48 hours instead of the 48-hour continuous infusion stated in the protocol?
There is increasing evidence that the mode of administration plays an important role for doxorubicin-induced cardiotoxicity and data indicate that bolus administration rather than continuous infusion appears to be an important risk factor.
In EURAMOS 1 it is mandatory to give doxorubicin as a 48 hour continuous iv infusion and therefore all patients should have a central line.
Q.32 Is it possible to continue on trial without using dexrazoxane if left ventricular ejection fraction falls?
Cumulative, dose-related anthracycline-induced cardiac toxicity is a serious, significant limiting side effect of its use.
Cardiac toxicity occurs in 1 to 2% of patients given a cumulative dose of <450mg/m2 and in 20 to 40% at doses >600mg/m2.
Children and adolescents appear to be particularly sensitive to cardiotoxic effects.
The degree of endomyocardial injury has been correlated with dose and schedule of administration.
Less severe injury is associated with lower cumulative dose, administration using a weekly schedule and administration using a continuous infusion.
As explained in Appendix A.5, dexrazoxane is converted intracellularly to a chelating agent that interferes with iron mediated free radical generation which is thought to be responsible, in part, for anthracycline-induced cardiomyopathy.
In EURAMOS 1, if a confirmed 10% fall within the normal range of left ventricular EF or FS occurs, our standard practice is to give dexrazoxane as instructed in the protocol section 9.1.8.4.6 and in Appendix A.5 and B.6.
Dexrazoxane is supplied in the UK under ""named patient basis"" by Chiron Biopharmaceuticals Limited, tel 0208 5804040.
It costs £124 (+ VAT) per 500mg.
It would be better to contact Chiron Biopharmaceuticals Limited before-hand to find out how many days are required for drug delivery for each individual site.
Q.33 Is carboxypeptidase mandatory in the case of delayed methotrexate elimination or methotrexate-related renal toxicity?
MTX is primarily cleared by renal excretion. Despite hyperhydration and urinary alkalinisation, MTX and its metabolites may precipitate in the renal tubules causing acute renal dysfunction.
This can be life-threatening, because it delays MTX excretion, thereby exacerbating other toxicities associated with MTX, especially myelosuppression, mucositis.
In a recent review of 3887 patients with osteosarcoma who received HD-MTX, almost 2% develop nephrotoxicity.
The mortality rate among those patients was 4.4%. Dialysis-based methods of MTX removal have limited effectiveness in removing MTX.
However, a single intravenous dose of 50 units/kg of carboxypeptidase results in the reduction of plasma MTX levels to the non-toxic range within minutes, without causing toxicity (Widermann B et al. High-Dose Methotrexate-induced nephrotoxicity in patients with osteosarcoma, Cancer 2004;100:2222-32).
Carboxypeptidase (Voraxaze™) is supplied in the UK under ""named patient basis"".
Further information, guidelines on administration, supplier details etc could be found in Appendix A.5.
Protherics plc, the manufacturer of Voraxaze™ (carboxypeptidase G2) has contracted with IDIS in the UK.
Registration with IDIS in advance of ordering is necessary to quickly process your request.
They deliver Voraxaze within 24 hrs of receipt of your order. It is supplied in packs of 2 vials containing 1000 IU per vial. The cost of 2 vial pack is £9440 + VAT.
This will effectively mean next day delivery and there will be a service during weekends and holidays (there may be an additional charge for this weekend service).
Contact telephone number for IDIS for information or order enquiries about Voraxaze: 01932 824 100.
Email contact during business hours: enquiries@idispharma.com,
Out of hours emergency line: 01932 824 198.
Q.34 Could different folinic acid rescue regimen be used than the one stated in the protocol?
Different FAR doses result in different level of rescue.
It is important to follow similar practice for all patients.
The guidelines in B.6 should be followed for all EURAMOS 1 patients.
Q.35 “Urinary electrolyte wasting” is one of the adverse events mentioned on the chemotherapy form. What does it refer to?
Urinary electrolyte wasting (see EURAMOS 1 protocol: Appendix A.4, page 41) refers to the inability of the kidneys to excrete acid into the urine.
This condition is called renal tubular acidosis and can be triggered by several drugs, including chemotherapy drugs. It may also be hereditary (i.e. Fanconi's syndrome), triggered by an autoimmune disease, or caused by heavy metal poisoning diabetes, sickle cell disease or an obstruction in the urinary tract.
Resulting symptoms and metabolic abnormalities include:
a) high blood acidity, e.g. low bicarbonate
b) mild dehydration
c) low or high potassium blood levels (depending of the type of renal tubular acidosis)
d) fragile bones and bone pain
e) kidney stones due to calcium deposits in the kidneys
The grading of this AE is as follows:
grade 1: asymptomatic, intervention not indicated
grade 2: mild, reversible and manageable with replacement
grade 3: irreversible, requiring continued replacement
grade 4: not applicable
grade 5: not applicable
Management depends on the type of renal tubular acidosis. It usually involves oral sodium bicarbonate supplements. Potassium supplements may also be required.
If potassium blood levels are high they can usually be kept under control by restricting the potassium intake and, if necessary, taking diuretics.
Q.36 How frequently should Glomerular Filtration Rate (GFR) be measured directly by radionuclide determination?
The measurement of GFR is necessary prior to each chemotherapy course.
It can be calculated by estimation (see Appendix A.3 for suggested formulae) or direct measurement by radionuclide estimation.
This a suggested schedule for direct measurement of GFR:
MAP /MAPifn arm: pre treatment, pre cycle 3, 5 and at the end of MAP chemotherapy;
MAPIE arm: pre treatment, pre cycle 3, 6, 8 and at end of treatment.
Q.37 Can the dose of Peg interferon can be rounded up or down to the nearest dose
SCENARIO 1: Patient's weight 54 kg on 0.5 micrograms/kg The dose will be 27 micrograms. If a 50 micrograms per 0.5 ml vial is supplied, the dose will be 0.27 mls. We would not round this up to 0.3 mls. SCENARIO 2: Patient's weight 54 kg on 1 micrograms/kg The dose will be 54 micrograms. If a 100 micrograms per 0.5 ml vial is supplied, the dose will be 0.27 mls. We would not round this up to 0.3 mls. SCENARIO 3: Patient's weight 53 kg on 0.5 micrograms/kg The dose will be 26.5 micrograms. If a 50 micrograms per 0.5 ml vial is supplied, the dose will be 0.265 mls. We would round this up to 0.27 mls. SCENARIO 4: Patient's weight 53kg on 1 micrograms/kg The dose will be 53 micrograms. If a 100 micrograms per 0.5 ml vial is supplied, the dose will be 0.265 mls. We would round this up to 0.27 mls.
Q.38 If a patient does not complete their 2 cycles of chemo before surgery are they ineligible for randomisation?
According to the protocol randomisation criteria (version 1.3, 31 July 2007, page 22, section 6.2) in order for a patient to be eligible for randomization they need along others to have had: 1. Exactly 2 courses of cisplatin and doxorubicin prior to surgery 2. Al least 2 courses and no more than 6 courses of methotrexate prior to surgery.
Q.39 On page 24 of the protocol 8.2.4, recommended baseline assessment of organ function, asks for an ECHO. However, this is not included in 8.3.4, after last cycle of chemotherapy. 8.4.2 Toxicity/Late Effects Related Follow Up includes ECHO as one of the investigations that is required to be performed annually. Is it an omission from 8.3.4, should an ECHO be included in the investigations required after the last cycle of chemotherapy?
Cardiac function should be assessed at the end of MAP or MAPIE chemotherapy and on annual basis thereafter.
Q.40 Should neutropenic sepsis be reported as an SAE?
Unless there is prolonged hospitalisation approximating a week or more then no SAE is required.
Q.41 What is the definition of progressice disease?
According to Appendix A.6, progressive disease is defined as "an increase of =20% in any dimension of the primary tumour when assessed radiologically IN ASSOCIATION WITH clinical features of progression such as increased pain, inflammatory signs, rising ALP. Assessment must be repeated in no less than 3 weeks to be regarded as progressive disease."
Q.42 If a patient does not complete their 2 cycles of chemo before surgery are they ineligible for randomisation?
If a patient does not complete their 2 cycles of chemo before surgery are they ineligible for randomisation? According to the protocol randomisation criteria (version 1.3, 31 July 2007, page 22, section 6.2) in order for a patient to be eligible for randomization they need along others to have had: 1. Exactly 2 courses of cisplatin and doxorubicin prior to surgery 2. Al least 2 courses and no more than 6 courses of methotrexate prior to surgery.
Q.43 Can the dose of Peg interferon be rounded up or down to the nearest dose?
1 ml syringes are used. Here are some examples: SCENARIO 1: Patient's weight 54 kg on 0.5 micrograms/kg The dose will be 27 micrograms. If a 50 micrograms per 0.5 ml vial is supplied, the dose will be 0.27 mls. We would not round this up to 0.3 mls. SCENARIO 2: Patient's weight 54 kg on 1 micrograms/kg The dose will be 54 micrograms. If 100 micrograms per 0.5 ml vial is supplied, the dose will be 0.27 mls. We would not round this up to 0.3 mls. SCENARIO 3: Patient's weight 53 kg on 0.5 micrograms/kg The dose will be 26.5 micrograms. If 50 micrograms per 0.5 ml vial is supplied, the dose will be 0.265 mls. We would round this up to 0.27 mls. SCENARIO 4: Patient's weight 53kg on 1 micrograms/kg The dose will be 53 micrograms. If 100 micrograms per 0.5 ml vial is supplied, the dose will be 0.265 mls. We would round this up to 0.27 mls.
Q.44 How should blood samples for the biological studies be stored?
There is no central storage for bloods for biological studies in the UK. Blood samples from EURAMOS 1 patients should be processed for DNA analysis and stored locally if there is an established facility for analysis in the centre. If they cannot be processed locally then they should be discarded.
Q.45 Methotrexate dose: should it be capped in patients with surface area >2 m2?
The EURAMOS-1 protocol states that doses should not be capped (please refer to section 9.1.8, pg 31 of v1.3 protocol). Drug dosage should be modified as little as possible and if necessary, treatment should be delayed in order to administer full doses.
Q.46 How often should heart function be checked?
Pre and during chemotherapy (see 9.1.8.1.3., page 32 of the protocol) EURAMOS 1 patients require ECHO or MUGA pre doxorubicin (pre cycle 1) and beyond cumulative dose of 300mg/m2, ie pre cycle 5 and pre cycle 6. Anaesthetists may request an ECHO or MUGA pre surgery, ie post cycle 2. At the end and after chemotherapy (ee section 8.4.2., page 25 of the protocol) Also an ECHO or MUGA is required at the end of chemotherapy (ie post cycle 6) and (providing the end of treatment scan is normal) annually for minimum of 5 years
Q.47 Patient started interferon in March ’07. At the end of December 2007 the patient decided for social reasons to discontinue treatment with interferon. In May 2008 the patient requested to restart interferon and continue with the trial. Is this possible?
Unfortunately, as termination of protocol treatment was because of patient’s preference, return to treatment cannot really be considered after such a long interruption.
Q.48 We have a patient on EURAMOS 1 who should be having surgery this week but not sure if this is going to go ahead. Should we be giving additional methotrexate if surgery is delayed?
Patients should have no more than six courses of methotrexate (MTX) administered before surgery to be eligible for randomization. If the patient has already had 4 courses of MTX (i.e. in cycle 1 and 2) then another 2 courses of MTX could be given before surgery. If given, this additional MTX should be recorded on the Chemotherapy form for cycle 2 (questions 14-16 should be answered).
Q.49 Should a patient who developed acute renal failure induced by high dose methotrexate and required glucarpidase rescue be re-challenged with methotrexate assuming good full renal recovery?
Patients who develop acute renal failure induced by high dose methotrexate should not be re-challenged with methotrexate unless there has been an obvious precipitating factor which could be avoided.
Q.50 Is audiometry assessment at baseline essential?
Audiometry is not essential for registration to EURAMOS 1. Therefore the patient could be registered even if audiometry has not been organised. However, audiometry is a recommended baseline assessment (protocol v1.3, section 8.2.4, page 24) prior to cisplatin, so I strongly recommend that it is arranged as soon as possible. If it is not possible to be arranged prior to next Tuesday then it should be arranged before the next cycle at the latest.
Q.51 What tests should be done for the urine phosphate and creatinine assessment?
The urine phosphate and creatinine is needed for measurement of tubular phosphate reabsorption (Tmp/GFR), see appendix A.3. It requires a urine sample to be sent to biochemistry lab for urine phosphate and urine creatinine. Centers should talk to their biochemistry lab before sending the sample. Measurement of tubular phosphate reabsorption (Tmp/GFR) is optional. It is recommended at the end of chemotherapy; see protocol v1.3, section 8.3.4, page 24 and appendix A.
Q.52 Interferon alfa-2b and Male Fertility
There have been very rare cases of a drop in sperm count in men who have been treated with interferon alfa-2b. This is probably due to the anti-proliferative effects of interferon alfa-2b and appears to be a non-permanent effect. To date there is no evidence that interferon alfa-2b will have any genetic effect on the sperm. The difficulty generally would be in knowing if the patient had a fertility problem prior to commencement of interferon therapy, however, if the effect is related to the interferon treatment, we would expect to see sperm counts resolving within 3 months of discontinuation of therapy. There have been a couple of reports where interferon alfa-2b has been used in the treatment of male fertility: 1. Yamamoto M, Miyake K, Successful use of interferon for male infertility, Lancet 344 (August 27): 614, 1994 2. Foresta C, Rossato M, Caution in the use of interferon for male infertility, Lancet 344 (October 8): 1027, 1994
Q.53 Could we perform a PET scan instead of bone scan for staging? Would that be acceptable to you?
Since the contribution of PET imaging in osteosarcoma (diagnosis-staging, response assessment and restaging in case of relapse) is not established yet, it would be better if patients have a baseline bone scan.
Q.54 Do we collect CRFs for patients who refuse randomization? I thought that we do. What about QOL forms?
Yes we still like to collect CRFs for patients not randomized. We request: Registration Form 1, Randomization Form 2, Chemotherapy Form 3 (Cycles 1&2 only), Follow Up Form 6 (Years 1-6, every 6 months - from time of biopsy), Event Form 7, QOL and Pathology Request Letter (they are listed on p10 of appendix B if that helps).
Q.55 I am arranging follow up for patient who is on the euramos trial. I notice that an Echo cardiogram and hearing test need doing every 12 months. However, this does not coincide with out patient appointment by a few months. Can I do scans to correspond with outpatients appointment and gradually bring them into line?
The end of treatment tests are described in section 8.3.4 page 24 of the protocol (version 1.3, 31 July 2007). You need to add the heart function to this list as described in section 8.4.2. page 25. After the end of treatment tests patients need yearly blood chemistry and heart function assessment together with radiology assessments as described in section 8.4.1.1, page 25 of the protocol. Patients do not have a hearing test every year after the end of treatment but only at the end of treatment, unless of course this is abnormal. There is no problem arranging all tests so they coincide with outpatient clinic appointments.