Neoplasms

All Conditions

Rare Diseases

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Germ Cells Tumors

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

Anti-Infective Agents

Paclitaxel

Albumin-Bound Paclitaxel

Oxaliplatin

Methotrexate

Dactinomycin

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

GAMMA Coordinator

Hayley Cartwright

GAMMA coordinator

Jonathan Shamash, MD FRCP

Jonathan Dr Shamash

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.

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

Barts & The London NHS Trust

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Testicular Neoplasms

Endocrine Gland Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Male Urogenital Diseases

Endocrine System Diseases

Testicular Diseases

Gonadal Disorders

Micronutrients

Hematinics

Vitamins

Etoposide

Cisplatin

Epirubicin

Lenograstim

Etoposide phosphate

Antimetabolites

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Immunosuppressive Agents

Immunologic Factors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Folinic Acid

Folate

Vitamin B9

Day 4 PEG Filgrastim 6mg Day 1 Actinomycin D 1mg/m2 Day 1 Methotrexate (dependent on creatinine clearance) Days 1,2, 3, 4 Etoposide 90mg/m2 Days 2, 3 Cisplatin 50mg/m2 Day 8 Cisplatin 50mg/m2 (cycle 1\&2 only)

Day 1 Actinomycin-D 1m/m2 Day 2, 3 and 8 Methotrexate 8g/m2 (dependent on creatinine clearance) Day 2, 3 and 8 Cisplatin 50mg/m2 (Day 8 dose omitted from week 6 onwards) Day 1 and 2 Epirubicin 37.5mg/m2 Day 3 Pegfilgrastim 6mg Treatment given on weeks 1, 3, 6, 8 and 10.

Pegfilgrastim

Doses are titrated against renal function. Dosage: 30 mins loading plus 12 hour infusion

Jonathan Shamash

St Bartholomew's hospital completed a study using the regimen GAMEC (PEG-filgrastim, actinomycin-D, methotrexate, etoposide, cisplatin). The results of this study showed that 50% of patients with relapsed testicular cancer could be cured using this treatment. These results are very encouraging and compare very favourably to other treatment protocols. In reviewing this study, it became clear that of the 5 cycles of treatment which were proposed, the first 3 seemed to matter and the last 2 did not appear important. In addition there was a group of patients who appeared to do particularly well namely patients under the age of 35 and those who had a normal LDH (lactate dehydrogenase). LDH is a blood test which monitors cancer activity. Selecting patients which fill both these criteria, this trial aims to see whether the investigators can maintain the good results the investigators have seen but using only 3 cycles of treatment. This will therefore shorten the treatment from 10 weeks to 6 weeks, thus reducing the side effects.

GAMEC-II (GAMEC -S \& GAMEC-A) is an open-labelled, non-randomised clinical trial in patients with relapsed germ cell tumours (GCT) and its objectives are:

1. To establish the response rates to GAMEC-S or GAMEC-A
2. To establish the safety and efficacy of substitution of epirubicin for etoposide (GAMEC-A regimen)
3. To establish the toxicity of GAMEC-A
4. To establish progression free survival (PFS)
5. To establish whether shortening GAMEC-S in patients without adverse prognostic factors reduces toxicity without compromising survival.

GAMEC-II, Risk-adapted Protocol for Relapsed Germ Cell Tumours (GCT)

GAMEC-SHORT (S) & GAMEC-ANTHRACYCLINE(A) (Combination Chemotherapy With GCSF, Actinomycin-D, Methotrexate, Etoposide and Cisplatin) Risk-adapted Protocol for Relapsed Germ Cell Tumours (GCT)

Tumour markers, clinical and radiological assessment of disease and/or examination of resected tissue (if surgery is done)

CT-scan chest, abdomen and pelvis (continued pelvic scanning is dependent whether disease present)

Queen Mary University of London

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Novel Single Arm Phase II Study for Relapsed Germ Cell Tumours With Poor Prognosis	NCT01782339	Germ Cell Tumou...	Combination Che...	16 Years - 65 Years	Barts & The London NHS Trust
A Novel Single Arm Phase II Study for Relapsed Germ Cell Tumours With Poor Prognosis	NCT01782339	Germ Cell Tumou...	Combination Che...	16 Years - 65 Years	Barts & The London NHS Trust
GAMEC-II, Risk-adapted Protocol for Relapsed Germ Cell Tumours (GCT)	NCT06309732	Testicular Neop...	Pegfilgrastim Dactinomycin Methotrexate Etoposide Cisplatin Epirubicin	16 Years - 35 Years	Queen Mary University of London

Spots Global Cancer Trial Database for germ cell tumour