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Phase 3 Accelerated BEP Trial:A randomised phase 3 trial of accelerated versus standard BEP chemotherapy for patients with intermediate and poor-risk metastatic germ cell tumours

Phase 3
Recruiting
Conditions
Intermediate and poor-risk metastatic germ cell tumours (GCTs)
Cancer - Testicular
Cancer - Other cancer types
Registration Number
ACTRN12613000496718
Lead Sponsor
niversity of Sydney
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Recruiting
Sex
All
Target Recruitment
500
Inclusion Criteria

1. Age greater than or equal to 11 years and less than or equal to 45 years on the date of randomisation
2. Histologically or cytologically confirmed germ cell tumour (non-seminoma or seminoma), except in the rare case of exceptionally raised tumour markers (AFP greater than or equal to 1000ng/mL and/or beta-HCG greater than or equal to 5000 IU/L) without histologic or cytologic confirmation 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 modified IGCCC classification (modified with different LDH criteria for intermediate risk non-seminoma, and inclusion of ovarian primaries).
6. Adequate bone marrow function with ANC greater than or equal to 1.0 x 10^9/L, Platelet count greater than or equal to 100 x 10^9/L
7. Adequate liver function where bilirubin must be less than or equal to 1.5 x ULN, ALT and AST must be less than or equal to 2.5 x ULN; except if the elevations are due to hepatic metastases, in which case ALT and AST must be less than or equal to 5 x ULN
8. Adequate renal function of GFR greater than or equal to 60 ml/min. It is recommended that GFR is estimated with the Cockcroft-Gault formula, unless calculated to be less than 60 ml/min or borderline in which case by 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. History of a malignancy prior to registration except for germ cell tumour or non-melanomatous carcinoma of the skin
2. Previous chemotherapy or radiotherapy, except (a)participants with pure seminoma relapsing after radiotherapy or adjuvant chemotherapy with 1-2 doses of single agent carboplatin, (b)participants with NSGCT and poor prognosis by IGCCC criteria receiving pre-protocol chemotherapy (eg. low-dose platinum and etoposide, baby-BOP) , (c)Participants who need to start therapy urgently prior to completing study-specific baseline investigations may commence study chemotherapy prior to registration and randomisation.
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 greater than or equal to grade 2 or clinically significant sensori-neural 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 have been surgically sterilised or use a double barrier method of contraception
8. Known allergy or hypersensitivity to any of the study drugs
9. Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule, including alcohol dependence or drug abuse

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Primary Outcome 1: comparison of the two treatment arms with respect to change in size of measurable tumour masses, changes in serum tumour markers and the results of surgical resection of residual masses after chemotherapy.<br><br>Outcomes will be assessed via the following tools and/or tests: CT scan, blood serum assay and histopathological results from surgery and biopsy.<br><br>[ Timepoint: at two years after randomisation of all planned participants.]
Secondary Outcome Measures
NameTimeMethod
Secondary Outcome: Adverse events (worst grade according to NCI CTCAE v4.03)[ Timepoint: 2 years after randomisation of all planned participants];Secondary Outcome: Health-related quality of life (Summary scales from QLQ-C30 & -TC14)[ Timepoint: 2 years after randomisation of all planned participants];Secondary Outcome: Treatment preference (Proportion preferring each treatment arm)[ Timepoint: 2 years after randomisation of all planned participants];Secondary Outcome: Delivered dose-intensity of chemotherapy (Relative to standard BEP)[ Timepoint: 2 years after randomisation of all planned participants]
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