- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01782339
A Novel Single Arm Phase II Study for Relapsed Germ Cell Tumours With Poor Prognosis (GAMMA)
Study Overview
Detailed Description
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.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: GAMMA Coordinator
- Phone Number: +44 (0)20 7882 8762
- Email: bci-gamma@qmul.ac.uk
Study Contact Backup
- Name: Hayley Cartwright
- Phone Number: +44 (0)20 7882 8196
- Email: h.cartwright@qmul.ac.uk
Study Locations
-
-
-
London, United Kingdom, EC1A 7BE
- Recruiting
- St Bartholomew's Hospital
-
Contact:
- GAMMA coordinator
-
Principal Investigator:
- Jonathan Shamash, MD FRCP
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Combination Chemotherapy
4 cycles of: Day 1 Actinomycin D 1mg/m2, Paclitaxel 80mg/m2, Methotrexate Day 4 Oxaliplatin 100mg/m2 Pegfilgrastim 6mg Day 8* Paclitaxel 80mg/m2 Day 15 Paclitaxel 80mg/m2 *Day 8 will be omitted for the first three patients treated in this study and will be given at the end of treatment in a fifth cycle where Paclitaxel 80mg/m2 will be administered on Days 1, 8, 15 and 22. Before adding the extra Paclitaxel 80mg/m2 dose on day 8 the safety data for these patients will be reviewed by a DMC. NB This 5th cycle for patients 1-3 has been included to ensure that the four 'missed doses of paclitaxel are not omitted from the patients treatment regimen. Cycles 1-4 are 21 days cycles; Cycle 5 (for the first three patients only) is a 28 day cycle. |
4 cycles of: Day 1 Actinomycin D 1mg/m2, Paclitaxel 80mg/m2, Methotrexate Day 4 Oxaliplatin 100mg/m2 Pegfilgrastim 6mg Day 8* Paclitaxel 80mg/m2 Day 15 Paclitaxel 80mg/m2 *Day 8 will be omitted for the first three patients treated in this study and will be given at the end of treatment in a fifth cycle where Paclitaxel 80mg/m2 will be administered on Days 1, 8, 15 and 22. Before adding the extra Paclitaxel 80mg/m2 dose on day 8 the safety data for these patients will be reviewed by a DMC. NB This 5th cycle for patients 1-3 has been included to ensure that the four 'missed doses of paclitaxel are not omitted from the patients treatment regimen. Cycles 1-4 are 21 days cycles; Cycle 5 (for the first three patients only) is a 28 day cycle. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Objective response rate
Time Frame: 2 years
|
2 years
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Progression Free Survival
Time Frame: 2 years
|
2 years
|
Overall Survival
Time Frame: 2 years
|
2 years
|
Toxicity Level
Time Frame: 2 years
|
2 years
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Jonathan Dr Shamash, Barts & The London NHS Trust
Publications and helpful links
General Publications
- Simon R. Optimal two-stage designs for phase II clinical trials. Control Clin Trials. 1989 Mar;10(1):1-10. doi: 10.1016/0197-2456(89)90015-9.
- Bedano PM, Brames MJ, Williams SD, Juliar BE, Einhorn LH. Phase II study of cisplatin plus epirubicin salvage chemotherapy in refractory germ cell tumors. J Clin Oncol. 2006 Dec 1;24(34):5403-7. doi: 10.1200/JCO.2006.05.8065.
- Haba Y, Williams MV, Neal DE, Ong JY, Ostrowski MJ, Ell PJ, Nargund V, Shamash J, Oliver RT. Stage migration and pilot studies of reduced chemotherapy supported by positron-emission tomography findings suggest new combined strategies for stage 2 nonseminoma germ cell tumour. BJU Int. 2008 Mar;101(5):570-4. doi: 10.1111/j.1464-410X.2007.07387.x.
- Pectasides D, Pectasides M, Farmakis D, Aravantinos G, Nikolaou M, Koumpou M, Gaglia A, Kostopoulou V, Mylonakis N, Economopoulos T, Raptis SA. Oxaliplatin and irinotecan plus granulocyte-colony stimulating factor as third-line treatment in relapsed or cisplatin-refractory germ-cell tumor patients: a phase II study. Eur Urol. 2004 Aug;46(2):216-21. doi: 10.1016/j.eururo.2004.03.001.
- Shamash J, Powles T, Ansell W, Berney D, Stebbing J, Mutsvangwa K, Wilson P, Asterling S, Liu S, Wyatt P, Joel SP, Oliver RT. GAMEC--a new intensive protocol for untreated poor prognosis and relapsed or refractory germ cell tumours. Br J Cancer. 2007 Aug 6;97(3):308-14. doi: 10.1038/sj.bjc.6603865. Epub 2007 Jul 3. Erratum In: Br J Cancer. 2007 Oct 22;97(8):1188. Berney, Dan [added].
- Shamash J, Powles T, Mutsvangwa K, Wilson P, Ansell W, Walsh E, Berney D, Stebbing J, Oliver T. A phase II study using a topoisomerase I-based approach in patients with multiply relapsed germ-cell tumours. Ann Oncol. 2007 May;18(5):925-30. doi: 10.1093/annonc/mdm002. Epub 2007 Mar 12.
- Theodore C, Chevreau C, Yataqhene Y, Fizazi K, Delord JP, Lotz JP, Geoffrois L, Kerbrat P, Bui V, Flechon A. A phase II multicenter study of oxaliplatin in combination with paclitaxel in poor prognosis patients who failed cisplatin-based chemotherapy for germ-cell tumors. Ann Oncol. 2008 Aug;19(8):1465-1469. doi: 10.1093/annonc/mdn122. Epub 2008 Apr 2.
- Gerlinger M, Wilson P, Powles T, Shamash J. Elevated LDH predicts poor outcome of recurrent germ cell tumours treated with dose dense chemotherapy. Eur J Cancer. 2010 Nov;46(16):2913-8. doi: 10.1016/j.ejca.2010.07.004. Epub 2010 Aug 13.
- International Prognostic Factors Study Group, Lorch A, Beyer J, Bascoul-Mollevi C, Kramar A, Einhorn LH, Necchi A, Massard C, De Giorgi U, Flechon A, Margolin KA, Lotz JP, Germa Lluch JR, Powles T, Kollmannsberger CK. Prognostic factors in patients with metastatic germ cell tumors who experienced treatment failure with cisplatin-based first-line chemotherapy. J Clin Oncol. 2010 Nov 20;28(33):4906-11. doi: 10.1200/JCO.2009.26.8128. Epub 2010 Oct 18.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 007755
- 2010-022795-31 (EudraCT Number)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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