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Accelerated v's Standard BEP Chemotherapy for Patients With Intermediate and Poor-risk Metastatic Germ Cell Tumours

PHASE3RECRUITING

The purpose of this study is to determine whether accelerated BEP chemotherapy is more effective than standard BEP chemotherapy in males with intermediate and poor-risk metastatic germ cell tumours.

Study details:

Bleomycin, Etoposide, Cisplatin (BEP) administered 3-weekly x 4 remains standard 1st line chemotherapy for intermediate- and poor-risk metastatic germ cell tumours (GCTs). Cure rates are over 90% for good-risk disease, 85% with intermediate-risk, and about 70% for poor-risk disease. Previous strategies to improve first-line chemotherapy have failed to improve cure rates and were more toxic than BEP.

New strategies are needed for patients with intermediate and poor-risk disease. BEP is accelerated by cycling Cisplatin and etoposide 2-weekly instead of 3-weekly. The Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) is conducting a trial comparing accelerated BEP with standard BEP.

The aim of this study is to determine if accelerated BEP is superior to standard BEP as first-line chemotherapy for intermediate and poor risk metastatic GCTs.

Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

  1. Age ≥ 11 years and ≤ 50 years on the date of randomisation
  2. Histologically or cytologically confirmed germ cell tumour (non-seminoma or seminoma); or Exceptionally raised tumour markers (AFP ≥ 1000ng/mL and/or HCG ≥ 5000 IU/L) without histologic or cytologic confirmation in the rare case where pattern of metastases consistent with GCT, high tumour burden, and a need to start therapy urgently
  3. Primary arising in testis, ovary, retro-peritoneum, or mediastinum
  4. Metastatic disease or non-testicular primary
  5. Intermediate or poor prognosis as defined by IGCCC classification3 (modified with different LDH criteria for intermediate risk non-seminoma, and inclusion of ovarian primaries). (See protocol for more information).
  6. Adequate bone marrow function with ANC ≥1.0 x 10^9/L, Platelet count ≥100 x 10^9/L
  7. Adequate liver function where bilirubin must be ≤1.5 x ULN, except participants with Gilbert's Syndrome where bilirubin must be ≤2.0 x ULN; ALT and AST must be ≤2.5 x ULN, except if the elevations are due to hepatic metastases, in which case ALT and AST must be ≤ 5 x ULN
  8. Adequate renal function with estimated creatinine clearance of ≥60 ml/min according to the Cockcroft-Gault formula, unless calculated to be < 60 ml/min or borderline in which case GFR should be formally measured, eg. with EDTA scan
  9. ECOG Performance Status of 0, 1, 2, or 3
  10. Study treatment both planned and able to start within 14 days of randomisation.
  11. Willing and able to comply with all study requirements, including treatment, timing and nature of required assessments
  12. Able to provide signed, written informed consent

Exclusion criteria

  1. Other primary malignancy (EXCEPT adequately treated non-melanomatous carcinoma of the skin, germ cell tumour, or other malignancy treated at least 5 years previously with no evidence of recurrence)
  2. Previous chemotherapy or radiotherapy, except if patient has pure seminoma relapsing after adjuvant radiotherapy or adjuvant chemotherapy with 1-2 doses of single agent carboplatin or if patient hasb. non-seminoma by IGCCC criteria or stage IV malignant ovarian germ cell tumour in the rare case where low-dose induction chemotherapy is given prior to registration because patient is not fit enough to receive protocol chemotherapy (eg. organ failure, vena cava obstruction, overwhelming burden of disease). Acceptable regimens include cisplatin 20 mg/m2 days 1-2 and etoposide 100 mg/m2 days 1-2; carboplatin AUC 3 days 1-2 and etoposide 100 mg/m2 days 1-2; or baby-BOP.43 Patients must meet all other inclusion and exclusion criteria at the time of registration.
  3. Significant cardiac disease resulting in inability to tolerate IV fluid hydration for cisplatin
  4. Significant co-morbid respiratory disease that contraindicates the use of bleomycin
  5. Peripheral neuropathy ≥ grade 2 or clinically significant sensorineural hearing loss or tinnitus
  6. Concurrent illness, including severe infection that may jeopardize the ability of the participant to undergo the procedures outlined in this protocol with reasonable safety
  7. Inadequate contraception. Men must use 2 effective methods of contraception, including use of a condom, during chemotherapy and for a year after completing chemotherapy.
  8. Known allergy or hypersensitivity to any of the study drugs
  9. Presence of any psychological, familial, sociological or geographical condition that in the opinion of the investigator would hamper compliance with the study protocol and follow-up schedule, including alcohol dependence or drug abuse

Eligibility

Age eligible for study : NA

Healthy volunteers accepted : No

Gender eligible for study: ALL

Things to know

Study dates

Study start:

Primary completion:

Study completion finish:

study type

Study type

TREATMENT

phase

Phase

    PHASE3

trial

Study ID

NCT02582697

Intervention or treatment

DRUG: Bleomycin (active name: Bleomycin Sulfate)

DRUG: Etoposide

DRUG: Cisplatin

DRUG: Pegylated G-CSF (Pegfilgrastim)

DRUG: Filgrastim

Conditions

  • Germ Cell Tumor

  • Condition: Germ Cell Tumor

  • DRUG: Bleomycin (active name: Bleomycin Sulfate) and other drugs

  • Newcastle, New South Wales, Australia and more

  • Sponsor: University of Sydney

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Are you running this trial?

If you're a clinic or sponsor, you can claim this study

Research sites nearby

Closest Location:

Calvary Mater Newcastle

Select from list below to view details:

  • Calvary Mater Newcastle

    Newcastle, New South Wales, Australia

  • Royal North Shore Hospital

    St Leonards, New South Wales, Australia

  • Prince of Wales Hospital

    Sydney, New South Wales, Australia

  • Chris O'Brien Lifehouse

    Sydney, New South Wales, Australia

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Who is running the clinical trial?

UoS

University of Sydney

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/ArmIntervention/Treatment
ACTIVE_COMPARATOR: Standard Arm - Standard BEP
  • Participants 16 years or older will receive 4 cycles of Standard BEP as follows:
  • * Bleomycin 30,000 IU IV weekly for 3 doses
  • * Etoposide 100 mg/m2 IV on day 1 - 5
  • * Cisplatin 20 mg/m2 IV on day 1 - 5
  • * Pegylated G-CSF 6 mg SCI on day 6
  • Patients \< 16 years old and weighs ≥ 45 kg will receive:
  • * Bleomycin \*15,000 - 30,000 IU IV weekly for 3 doses
  • * Etoposide 100 mg/m2 IV on day 1 - 5
  • * Cisplatin 20 mg/m2 IV on day 1 - 5
  • * Pegylated G-CSF 6 mg SCI on day 6
  • Patients \<16 years old and weighs \< 45 kg will receive:
  • * Bleomycin \*15,000 - 30,000 IU IV weekly for 3 doses
  • * Etoposide 100 mg/m2 IV on day 1 - 5
  • * Cisplatin 20 mg/m2 IV on day 1 - 5
  • * Filgrastim 10mcg/kg/day on day 6, until post-nadir Absolute Neutrophil Count ≥1 x10\^9/ L
  • * The dose of bleomycin is decided by the treating physician and based on the patient's Body Surface Area.
  • Each cycle is 3 weeks (21 days).
  • The planned total duration of treatment is 12 weeks.
Drug: Bleomycin (active name: Bleomycin Sulfate), Drug: Etoposide, Drug: Cisplatin, Drug: Pegylated G-CSF (Pegfilgrastim), Drug: Filgrastim
    EXPERIMENTAL: Experimental Arm - Accelerated BEP
    • Participants 16years or older will receive 4 cycles of Accelerated BEP as follows:
    • * Bleomycin 30,000 IU IV wkly for 2 doses
    • * Etoposide 100 mg/m2 IV on day 1 - 5
    • * Cisplatin 20 mg/m2 IV on day 1- 5
    • * Pegylated G-CSF 6 mg SCI on day 6
    • Patients \<16years and weighs ≥45 kg will receive:
    • * Bleomycin \*15,000 - 30,000 IU IV wkly for 2 doses
    • * Etoposide 100 mg/m2 IV on day 1 - 5
    • * Cisplatin 20 mg/m2 IV on day 1 - 5
    • * Pegylated G-CSF 6 mg SCI on day 6
    • Patients \<16years and weighs \<45 kg will receive:
    • * Bleomycin \*15,000 - 30,000 IU IV wkly for 2 doses
    • * Etoposide 100 mg/m2 IV on day 1 - 5
    • * Cisplatin 20 mg/m2 IV on day 1 - 5
    • * Filgrastim 10mcg/kg/day on day 6, until ANC ≥1 x10\^9/ L
    • Each cycle is 2 weeks (14days)
    • Following 4xBEP cycles, patients will receive additional bleomycin as follows:
    • \- Bleomycin \*15,000 - 30,000 IU IV wkly for 4 doses
    • \* The dose of bleomycin is decided by the treating physician and based on the patient's BSA.
    • The planned total duration is 12 weeks.
    Drug: Bleomycin (active name: Bleomycin Sulfate), Drug: Etoposide, Drug: Cisplatin, Drug: Pegylated G-CSF (Pegfilgrastim), Drug: Filgrastim

      What is the study measuring?

      Primary Outcome

      MeasureDescriptionTime Frame
      Progression-free survival (disease progression or death)PFS is measured from the date of randomisation until the criteria for disease progression are met (as defined in the protocol) or death. Participants who are not observed to progress nor die will be censored at the date of last follow-upFrom randomisation up to disease progression or date of death whichever come first, assessed up to 5 years

      Secondary Outcome

      MeasureDescriptionTime Frame
      Initial response assessmentThe assessment of response of germ cell tumours is measured by the change in size of measurable tumour masses in combination with changes in serum tumour markers after chemotherapy treatment.At end of chemotherapy treatment, treatment planned for 12 weeks
      Final response assessmentThe assessment of response of germ cell tumours is measured by changes in serum tumour markers and imaging at 6 months from randomisation, or after any post-chemotherapy surgical resection or other intervention, whichever occurs last.At 6 months
      Adverse events (worst grade according to NCI CTCAE v4.03)The intensity of adverse events will be assessed using the NCI Common Terminology Criteria for Adverse Events version 4 (NCI CTCAE v4.03)From start of chemotherapy until 30 days after last dose, an average of 4 months
      Health-related quality of lifeHR-QoL measures will include the EORTC core quality of life questionnaire (QLQ-C30), a 30-item cancer-specific questionnaire that is well-validated and available in many languages.From date of randomisation until date of 18 month follow-up
      Health-related quality of life for testicular cancerEORTC quality of life module for testicular cancer (QLQ-TC26), a disease-specific measure with 26 items about physical symptoms, sexual functioning and emotional issues.From date of randomisation until date of 18 month follow-up
      Treatment preferenceA trial-specific preferences question will be used to determine if participants think they would prefer to be treated with accelerated BEP or standard BEP, assuming that they were equally effective.From date of randomisation until date of 18 month follow-up
      Delivered dose-intensity of chemotherapy (relative to standard BEP)Delivered dose-intensity of cisplatin, etoposide and bleomycin will be assessed.From start date of chemotherapy treatment until date of end of chemotherapy, an average of 12 weeks
      Overall survivalOverall survival is measured from the date of randomisation until death from any cause, or the date of last known follow-up alive.From randomisation up to disease progression or date of death whichever come first, assessed up to 5 years
      Are you running this trial?If you're a clinic or sponsor, you can claim this study.
      Claim this trial

      References

      Clinical Trials Gov: Accelerated v's Standard BEP Chemotherapy for Patients With Intermediate and Poor-risk Metastatic Germ Cell Tumours

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