IRB Study Number 18-1230
Status Recruiting
Phase Phase 3
Institutes Taussig Cancer Institute, Pediatric Institute
Description
Primary objectives
To determine if accelerated BEP (Bleomycin, Etoposide, cisPlatin) is superior to standard BEP as first-line chemotherapy for intermediate and poor-risk metastatic GCTs.
To compare the two treatment arms with respect to: Progression-free survival (disease progression or death)
Secondary objectives
To compare the two treatment arms with respect to:
2) Response following treatment completion (protocol-specific response criteria)
3) Adverse events (worst grade according to NCI CTCAE v4.03)
4) Health-related quality of life (Summary scales from QLQ-C30 & -TC-26)
5) Treatment preference (Proportion preferring each treatment arm)
6) Delivered dose-intensity of chemotherapy (Relative to standard BEP)
7) Overall survival (death from any cause)
Inclusion Criteria
Age ≥ 11 years and ≤ 45 years on the date of randomisation
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
Primary arising in testis, ovary, retro-peritoneum, or mediastinum
Metastatic disease or non-testicular primary
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 table below: (See protocol)
Adequate bone marrow function with ANC ≥1.0 x 109/L, Platelet count ≥100 x 109/L
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
Adequate renal function with estimated creatinine clearance of ≥60 ml/min according to the Cockcroft-Gault formula (see Appendix 5), unless calculated to be < 60 ml/min or borderline in which case GFR should be formally measured, eg. with EDTA scan
ECOG Performance Status of 0, 1, 2, or 3 (see Appendix 4)
Study treatment both planned and able to start within 14 days of randomisation.
Willing and able to comply with all study requirements, including treatment, timing and nature of required assessments
Able to provide signed, written informed consent
Exclusion Criteria
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)
Previous chemotherapy or radiotherapy, except:
a. pure seminoma relapsing after adjuvant radiotherapy or adjuvant chemotherapy with 1-2 doses of single agent carboplatin
b. non-seminoma and poor prognosis by IGCCC criteria 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.37 Patients must meet all other inclusion and exclusion criteria at the time of registration.
c. Participants who need to start therapy urgently prior to completing study-specific baseline investigations may commence study chemotherapy prior to registration and randomisation. Such patients must be discussed with the coordinating centre prior to registration, and must be registered within 10 days of commencing study chemotherapy.
Significant cardiac disease resulting in inability to tolerate IV fluid hydration for cisplatin
Significant co-morbid respiratory disease that contraindicates the use of bleomycin
Peripheral neuropathy ≥ grade 2 or clinically significant sensorineural hearing loss or tinnitus
Concurrent illness, including severe infection that may jeopardize the ability of the participant to undergo the procedures outlined in this protocol with reasonable safety
Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to registration..
Known allergy or hypersensitivity to any of the study drugs
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
