Talazoparib and Temozolomide in Treating Younger Patients With Refractory or Recurrent Malignancies
Condition: Adult Solid Neoplasm; Childhood Solid Neoplasm; Recurrent Childhood Central Nervous System Neoplasm; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Malignant Solid Neoplasm; Refractory Central Nervous System Neoplasm
MeSH terms: Neoplasms; Sarcoma, Ewing; Neuroectodermal Tumors; Neuroectodermal Tumors, Primitive; Neuroectodermal Tumors, Primitive, Peripheral; Nervous System Neoplasms; Central Nervous System Neoplasms; Recurrence
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This phase I/II trial studies the side effects and best dose of talazoparib and temozolomide
      and to see how well they work in treating younger patients with tumors that have not
      responded to previous treatment (refractory) or have come back (recurrent). Talazoparib may
      stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs
      used in chemotherapy, such as temozolomide, work in different ways to stop the growth of
      cancer cells, either by killing the cells, by stopping them from dividing, or by stopping
      them from spreading. Giving talazoparib together with temozolomide may work better in
      treating younger patients with refractory or recurrent malignancies.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. To estimate the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of
      temozolomide when combined with a dose of talazoparib (BMN 673) given once daily for 5 days
      after a one day dose of BMN 673 administered orally (either once daily or twice daily), every
      28 days to children with refractory or recurrent solid tumors. (Phase I) II. To define and
      describe the toxicities of BMN 673 given with temozolomide administered on this schedule.
      (Phase I) III. To characterize the pharmacokinetics of BMN 673 and temozolomide when given in
      combination to children with refractory or recurrent cancer. (Phase I) IV. To define the
      antitumor activity of BMN 673 when given with temozolomide in recurrent/refractory Ewing
      sarcoma.(Phase II)

      SECONDARY OBJECTIVES:

      I. To preliminarily define the antitumor activity of BMN 673 and temozolomide in pediatric
      patients with recurrent or refractory solid tumors within the confines of a phase I study.

      II. To explore possible predictive biomarkers in archival tumor tissue from Ewing sarcoma
      patients in Phase II.

      OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.

      Patients receive talazoparib orally (PO) once daily (QD) or twice daily (BID) on days 1-6 and
      temozolomide PO QD on days 2-6. Treatment repeats every 28 days for up to 24 courses in the
      absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 30 days.
    

Intervention name(s): Laboratory Biomarker Analysis; Pharmacological Study; Talazoparib; Temozolomide
Intervention type(s): Other; Other; Drug; Drug
Intervention description(s): Correlative studies; Correlative studies; Given PO; Given PO
Other intervention name(s): BMN 673; BMN-673; CCRG-81045; Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-; M & B 39831; M and B 39831; Methazolastone; RP-46161; SCH 52365; Temcad; Temodal; Temodar; Temomedac; TMZ
Intervention MeSH terms: Temozolomide; Talazoparib
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Treatment