A Novel Single Arm Phase II Study for Relapsed Germ Cell Tumours With Poor Prognosis

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