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

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Brief Title

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

Official Title

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

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.
    

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 Phase

Phase 2

Study Type

Interventional


Primary Outcome

Objective response rate

Secondary Outcome

 Progression Free Survival

Condition

Germ Cell Tumour

Intervention

Combination Chemotherapy

Study Arms / Comparison Groups

 Combination Chemotherapy
Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

43

Start Date

July 2012

Completion Date

January 2021

Primary Completion Date

January 2021

Eligibility Criteria

        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
      

Gender

All

Ages

16 Years - 65 Years

Accepts Healthy Volunteers

No

Contacts

Jonathan Dr Shamash, +44 (0)20 7882 8762, [email protected]

Location Countries

United Kingdom

Location Countries

United Kingdom

Administrative Informations


NCT ID

NCT01782339

Organization ID

007755

Secondary IDs

2010-022795-31

Responsible Party

Sponsor

Study Sponsor

Barts & The London NHS Trust


Study Sponsor

Jonathan Dr Shamash, Principal Investigator, Barts & The London NHS Trust


Verification Date

April 2019