ADVL1411 - A Phase I/II Study of BMN673 Plus Temozolomide

ADVL1411 - A Phase I/II Study of BMN673, an Oral Poly(ADP-Ribose) Polymerase Inhibitor, Plus Temozolomide in Children with Refractory or Recurrent Malignancies

Diseases

Patients with relapsed or refractory solid tumors, including CNS tumors, without bone marrow involvement. The Phase 2 part of the study will include patients with acute lymphoblastic leukemia (ALL) in 2^nd or greater relapse, excluding patients with CNS 3 status.

Description

BMN673 is an orally administered PARP inhibitor, which prevents DNA repair of tumor cells. Temozolomide is an orally administered alkylating agent, theorized to potentiate PARP inhibition. BMN673 will be given orally on Day 1 (either once or twice daily) followed by BMN673 and low dose temozolomide given together once per day on Days 2-6 of each 28-day cycle. In the absence of disease progression or significant toxicities, therapy may continue for up to 24 cycles.

Eligibility Criteria

• Phase I: Must be between 12 months and 21 years of age. Phase II: Must be between 12 months and 30 years of age.
• Phase 1: Patients who have received prior therapy with a PARP inhibitor and/or temozolomide are eligible provided they have not progressed on a regimen containing both these agents. Phase II: Patients previously treated with a PARP inhibitor are not eligible.
• Patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy and have the appropriate wash-out period from most recent cancer directed therapy (with some exceptions for patients with ALL).
• Must have adequate organ function as evidenced by laboratory criteria.
• Patients receiving corticosteroids must be on a stable or decreasing dose for at least 7 days prior to enrollment.
• Patients must be able to swallow capsules.
• Must not have an uncontrolled infection.
• Must not have received a prior solid organ transplantation.
• Must not have received prior TBI, craniospinal XRT, or > 50% radiation of the pelvis.
• Must not have known hypersensitivity to temozolomide or deacarbazine.

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