A Novel Single Arm Phase II Study for Relapsed Germ Cell Tumours With Poor Prognosis
A Novel Single Arm Phase II Study for Relapsed Germ Cell Tumours With Poor Prognosis
The treatment of germ cell tumours is considered to be one of the major successes in the area
 of cytotoxic chemotherapy. Even in patients who relapse after first line therapy, a durable
 remission rate of between 25% and 60% has been seen using further chemotherapy. In 1999,
 researchers at St Bartholomew's Hospital developed the GAMEC protocol (combination
 chemotherapy with filgrastim, actinomycin D, methotrexate, etoposide, cisplatin). Results
 from this study showed that 50% of patients with relapsed testicular cancer could be cured
 using this treatment. When we reviewed the individual patients it was clear that older
 patients (>35yrs) or patients with a raised Lactate Dehydrogenase (a blood test that monitors
 cancer activity), did not do as well. In addition, patients whose original tumour started in
 their chest (mediastinal germ cell tumour) have tended to do badly if they relapse. We have
 been developing a study for patients who fulfil at least one of these criteria. The GAMIO
 study (filgrastim, actinomycin D, methotrexate, irinotecan, oxaliplatin) has recently closed
 due to problems with high levels of toxicity from the irinotecan. GAMMA is a new study that
 will use paclitaxel instead of irinotecan and oxaliplatin instead of cisplatin. We expect
 that this treatment with oxaliplatin will be less damaging to the kidneys than cisplatin.
 Both oxaliplatin and paclitaxel and oxaliplatin and irinotecan have similar activity in
 relapsed patients in the phase II setting. We hope to improve on our previous results with
 this substitution and see if this will lead to an improvement in the cure rate of relapsed
 germ cell tumours with poor prognosis and reduce the side effects compared to our standard
 treatment. In addition, we do not expect any hearing damage and the treatment requires a
 shorter hospital stay.
Patients will receive a 4 drug combination chemotherapy in hospital over two nights. On the
 third day, the patient will receive an injection of pegfilgrastim. This stimulates the bone
 marrow to produce white blood cells and shortens the period of risk of serious infection. The
 treatment will be repeated every three weeks. This constitutes one cycle of treatment. We aim
 to give the patient four cycles of treatment over a total of twelve weeks.

 Before each cycle, the following will be conducted - physical examination, full blood count,
 urea + electrolytes, liver function tests, LDH, αFP, βHCG.

 Patients will have a FDG PET-CT scan at baseline, prior to cycle 2(approximately 1521 days
 after chemotherapy starts)and within 28 days of the last treatment, only if clinically
 indicated. On each cycle, serum creatinine should be measured 24 hours after the start of the
 methotrexate to exclude renal failure due to methotrexate.

 The following will be conducted at the end of treatment physical examination, full blood
 count, urea + electrolytes, liver function tests, LDH, αFP, βHCG. The patients will be
 monitored during chemotherapy and then monthly in the first year and two monthly in the
 second year.

 An interim analysis will be performed after 15 patients have completed treatment. If less
 than 9 responses are observed in this group, the study will be terminated. The final analysis
 will be performed after 43 patients have recruited, completed treatment and been followed for
 24 months.
Inclusion Criteria:

 -  Germ Cell Tumour (GCT)

 -  Relapsed or progression on or following platinum-based chemotherapy (rising tumour
 markers or progressive disease on PET CT Scan prior to entering study)

 -  Neutrophil count >1.0x109/l

 -  Platelets >70x109/l

 -  Haemoglobin >100g/l (may be transfused)

 -  Glomerular filtration rate >40ml/min (determined by EDTA clearance or calculated
 creatinine clearance using the Cockcroft - Gault equation if unable to perform EDTA
 clearance)

 -  Males and females aged 16-65 years

 a) Male patients must have IGCCCG2 prognostic score, low to very high

 -  Patients must be sterile or agree to use adequate contraception during the period of
 therapy

 -  ECOG Performance status 0-3

 -  Able and willing to give written informed consent and comply with the protocol study
 procedures.

 Exclusion Criteria:

 -  Other malignancy except basal cell carcinoma

 -  Significant co-morbidity likely to make delivery of this treatment unsafe

 -  Currently enrolled in any other investigational drug study

 -  Previous chemotherapy with oxaliplatin, methotrexate or Actinomycin D

 -  Patients who have peripheral neuropathy with functional impairment