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

NCT01782339 | Completed Phase 2 DMC

• 2 other identifiers: 0077552010-022795-31
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Germ Cell Tumour

Outcome Measures

Primary Outcomes (1)

• Objective response rate

  2 years

Secondary Outcomes (3)

• Progression Free Survival

  2 years

• Overall Survival

  2 years

• Toxicity Level

  2 years

Study Arms (1)

Combination Chemotherapy

EXPERIMENTAL

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.

Drug: Combination Chemotherapy

Interventions

Combination Chemotherapy DRUG

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.

Combination Chemotherapy

Eligibility Criteria

• Age: 16 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Barts & The London NHS Trust: lead

Study Sites (1)

St Bartholomew's Hospital

London, EC1A 7BE, United Kingdom

Location

Related Publications (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.

  PMID: 17135640 BACKGROUND

• 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.

  PMID: 18257857 BACKGROUND

• 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.

  PMID: 15245816 BACKGROUND

• 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.

  PMID: 17609665 BACKGROUND

• 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.

  PMID: 17355956 BACKGROUND

• 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.

  PMID: 18385203 BACKGROUND

• 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.

  PMID: 2702835 BACKGROUND

• 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.

  PMID: 20709529 BACKGROUND

• 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.

  PMID: 20956623 BACKGROUND

Related Links

• Related Info

MeSH Terms

Conditions

Neoplasms, Germ Cell and Embryonal

Interventions

Drug Therapy, Combination

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Drug Therapy; Therapeutics

Study Officials

• Jonathan Dr Shamash

  Barts & The London NHS Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2013
• First Posted: February 1, 2013
• Study Start: May 1, 2012
• Primary Completion: May 5, 2021
• Study Completion: May 5, 2021
• Last Updated: June 14, 2024

Record last verified: 2024-06

Locations

GB (1)