Durvalumab Alone or With Tremelimumab in Refractory Germ Cell Tumors (APACHE)

This is an interventional treatment trial for Germ Cell Tumor focused on measuring Immunotherapy, Durvalumab, Tremelimumab, Combination therapy, Testicular cancer Read More

Inclusion Criteria:

• Age ≥ 18 years
• Male of female gender.
• Histological or clinical diagnosis of GCT.
• Availability of archival tumor samples for local assessment (by immunohistochemistry) of PD-L1 expression.
• Either gonadal or extragonadal tumor primary.
• Failure of ≥2 prior chemotherapy regimens for metastatic disease (1-2 cycles of cisplatin, etoposide and bleomycin (PEB) or 1 cycle carboplatin area under the curve (AUC) 7 given in the adjuvant setting for clinical stage I disease will not be counted as prior lines).
• Failure of high-dose chemotherapy will be allowed.
• Brain metastases: patients who present with brain metastases as the sole site of disease relapse/progression are not allowed to enter the study. Otherwise, patients with metastatic disease including brain metastases will be allowed provided that they have been irradiated, are stable from at least 4 weeks, and a wash-out period from steroids has occurred (28 days).
• Subjects must provide written informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Adequate end-organ system function tests.
• See the study full protocol for durvalumab-specific and tremelimumab requirements.

Exclusion Criteria:

• Prior exposure to immune-mediated therapy, including but not limited to, other anti-Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4), anti-PD-1, anti-PD-L1, or anti-PD-L2 antibodies, including therapeutic anticancer vaccines.
• Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.
• Patients with Grade <2 neuropathy will be evaluated on a case-by-case basis after consultation with the Principal Investigator.
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included after consultation with the Principal Investigator.
• Any concurrent chemotherapy, biologic, or hormonal therapy for cancer treatment.
• History of allogenic organ transplantation that requires use of immunosuppressive agents.
• Active or prior documented autoimmune or inflammatory disorders.
• Active infection including active tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).
• Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab or tremelimumab.
• Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy or 180 days after the last dose of durvalumab + tremelimumab combination therapy.