Title
A Randomized Phase 3 Trial of Accelerated versus Standard BEP Chemotherapy for Patients with Intermediate and Poor-risk Metastatic Germ Cell Tumors

Description
Phase 3 Accelerated versus standard BEP chemotherapy for patients with intermediate and poor-risk metastatic germ cell tumors

Objective
The overall goal of this study is to determine whether accelerated BEP will be effective and well-tolerated for patients with advanced GCTs. We don’t yet know if accelerated treatment is helpful in advanced GCTs and we are hoping this study will answer that question

Treatment The 2 treatment plans are called Arm A and Arm B, as follows:

Arm A: Standard chemotherapy (bleomycin, etoposide, cisplatin, and pegfilgrastim or filgrastim) given in 3-week cycles

Arm B: Accelerated chemotherapy (bleomycin, etoposide, cisplatin, and pegfilgrastim or filgrastim) given in 2-week cycles, and followed by 4 weekly doses of bleomycin alone

Key Eligibility
Age greater than or equal to 11 years and less than or equal to 45 years

Histologically or cytologically confirmed germ cell tumour (non-seminoma or seminoma); or Exceptionally raised tumour markers (AFP greater than or equal to 1000ng/mL and/or HCG greater than or eqaul to 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 classification(modified with different LDH criteria for intermediate risk non-seminoma, and inclusion of ovarian primaries) Contact study coordinator for more information

Adequate bone marrow, liver and renal function as defined by the protocol

ECOG Performance Status of 0, 1, 2, or 3

EXCLUSION:

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: pure seminoma relapsing after adjuvant radiotherapy or adjuvant chemotherapy with 1-2 doses of single agent carboplatin, 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) Patients must meet all other inclusion and exclusion criteria at the time of registration

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 greater than or equal to grade 2 or clinically significant sensorineural hearing loss or tinnitus

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

Applicable Disease Sites
Bladder; Brain/Central Nervous System; Breast; Cervix; Colon and Rectum; Endocrine cancers; Esophagus; Gastrointestinal cancers, other; Genitourinary cancers, other; Head and Neck; Ill-Defined Sites; Kidney; Leukemia; Liver; Lung; Melanoma/Skin cancer; Ovary; Pancreas; Prostate; Sarcoma; Stomach; Thyroid; Uterus

Participating Institutions
Gundersen Health System; UW Health University Hospital