Germ Cell Tumor
Conditions
Keywords
Germ Cell, Intermediate and poor-risk metastatic germ cell tumours
Brief summary
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.
Detailed description
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.
Interventions
DRUGBleomycin (active name: Bleomycin Sulfate)
Standard Arm: Bleomycin 30,000 international units IV weekly for 3 doses (eg. days 1, 8 and 15 or days 2, 9 and 16 of a 21-day cycle) for 4 cycles. Accelerated Arm: Bleomycin 30,000 international units IV weekly for 2 doses (eg. days 1 and 8 or days 2 and 9 of a 14-day cycle) for 4 cycles. Followed by Bleomycin 30,000 international units IV weekly for 4 doses.
DRUGEtoposide
Standard Arm: Etoposide 100 mg/m2 IV on days 1, 2, 3, 4, 5 of a 21-day cycle for 4 cycles. Accelerated Arm: 100 mg/m2 IV on days 1, 2, 3, 4, 5 of a 14-day cycle for 4 cycles.
DRUGCisplatin
Standard Arm: Cisplatin 20 mg/m2 IV on days 1, 2, 3, 4, 5 of a 21-day cycle for 4 cycles. Accelerated Arm: Cisplatin 20 mg/m2 IV on days 1, 2, 3, 4, 5 of a 14-day cycle for 4 cycles.
DRUGPegylated G-CSF (Pegfilgrastim)
Standard Arm: 6 mg SCI on day 6 of a 21-day cycle for 4 cycles. Accelerated Arm: 6 mg SCI on day 6 of a 14-day cycle for 4 cycles.
DRUGFilgrastim
Standard Arm: 10 mcg/kg/day on day6, until post-nadir absolute neutrophil count ≥ 1.0 x 10\^9/L, of a 21-day cycle for 4 cycles. Accelerated Arm: 10 mcg/kg/day on day 6, until post-nadir absolute neutrophil count ≥ 1.0 x 10\^9/L, of a 14-day cycle for 4 cycles.
Sponsors
University of Sydney
Australian and New Zealand Urogenital and Prostate Cancer Trials Group
Cambridge University Hospitals NHS Foundation Trust
Cancer Trials Ireland
Children's Oncology Group
Dana-Farber Cancer Institute
University of Southern California
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
11 Years to 50 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (disease progression or death) | From randomisation up to disease progression or date of death whichever come first, assessed up to 5 years | 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-up |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Health-related quality of life | From date of randomisation until date of 18 month follow-up | HR-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. |
| Health-related quality of life for testicular cancer | From date of randomisation until date of 18 month follow-up | EORTC quality of life module for testicular cancer (QLQ-TC26), a disease-specific measure with 26 items about physical symptoms, sexual functioning and emotional issues. |
| Treatment preference | From date of randomisation until date of 18 month follow-up | A 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. |
| Delivered dose-intensity of chemotherapy (relative to standard BEP) | From start date of chemotherapy treatment until date of end of chemotherapy, an average of 12 weeks | Delivered dose-intensity of cisplatin, etoposide and bleomycin will be assessed. |
| Overall survival | From randomisation up to disease progression or date of death whichever come first, assessed up to 5 years | Overall survival is measured from the date of randomisation until death from any cause, or the date of last known follow-up alive. |
| Final response assessment | At 6 months | The 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. |
| Adverse events (worst grade according to NCI CTCAE v4.03) | From start of chemotherapy until 30 days after last dose, an average of 4 months | The intensity of adverse events will be assessed using the NCI Common Terminology Criteria for Adverse Events version 4 (NCI CTCAE v4.03) |
| Initial response assessment | At end of chemotherapy treatment, treatment planned for 12 weeks | The 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. |
Countries
Australia, New Zealand, United Kingdom, United States
Contacts
CONTACTP3BEP Trial Coordinator
CONTACTP3BEP Project Manager
STUDY_CHAIRPeter Grimison
Chris O'Brien Lifehouse
Outcome results
None listed