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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Children's Hospital of Alabama
Birmingham, Alabama, United States
Children's Hospital Los Angeles
Los Angeles, California, United States
Children's Hospital of Orange County
Orange, California, United States
UCSF Medical Center-Parnassus
San Francisco, California, United States
UCSF Medical Center-Mission Bay
San Francisco, California, United States
Children's Hospital Colorado
Aurora, Colorado, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois, United States
Riley Hospital for Children
Indianapolis, Indiana, United States
...and 12 more locations
The Number of Participants With Dose Limiting Toxicities to Determine the Maximum Tolerated Dose of Temozolomide and Talazoparib Combination Therapy
The Maximum Tolerated Dose (MTD) reflects the highest dose of Talazoparib (BMN 673) when combined with a dose of temozolomide that did not cause a Grade 3 or higher toxicity in children with refractory or recurrent solid tumors.
Time frame: 28 days
All Cycle 1 Toxicities >=Grade 3
The number of patients with at least one toxicity (DLT or non-DLT) in cycle 1 that is at least possibly attributable to study agent
Time frame: Up to 28 days
T Max of Talazoparib
Median with minimum and maximum for the time at which the maximum (peak) serum concentration occurs.
Time frame: Cycle 1 Day 1 pre-dose, and 1, 2, 4, 8 and 24 hours after the first talazoparib dose.
C Max of Talazoparib
Median with minimum and maximum for the time at which the maximum (peak) serum concentration occurs.
Time frame: Cycle 1 Day 1 pre-dose, and 1, 2, 4, 8 and 24 hours after the first talazoparib dose.
AUC of Talazoparib
Median with minimum and maximum for the area under the drug concentration over time curve.
Time frame: Cycle 1 Day 1 pre-dose, and 1, 2, 4 and 8 hours after the first talazoparib dose
Accumulation Half-life of Talazoparib in Combination With Temozolomide.
Median with minimum and maximum for the time required for the serum concentration to fall to 50% of its starting dose.
Time frame: Cycle 1 Day 1 pre-dose, and 1, 2, 4 and 8 hours after the first talazoparib dose. Day 5 or 6 pre-dose, and 1, 2, 4 and 8 hours after the talazoparib dose
T Max of Talazoparib in Combination With Temozolomide
Median with minimum and maximum for the time at which the maximum (peak) serum concentration occurs.
Time frame: Cycle 1 Day 5 or 6 pre-dose, and 1, 2, 4 and 8 hours after the talazoparib dose
C Max of Talazoparib in Combination With Temozolomide
Median with minimum and maximum for the time at which the maximum (peak) serum concentration occurs.
Time frame: Cycle 1 Day 5 or 6 pre-dose, and 1, 2, 4 and 8 hours after the talazoparib dose
AUC of Talazoparib in Combination With Temozolomide
Median with minimum and maximum area under the drug concentration over time curve
Time frame: Cycle 1 Day 5 or 6 pre-dose, and 1, 2, 4 and 8 hours after the talazoparib dose
Clearance of Talazoparib in Combination With Temozolomide
Median with minimum and maximum for the rate of elimination of the drug.
Time frame: Cycle 1 Day 5 or 6 pre-dose, and 1, 2, 4 and 8 hours after the talazoparib dose
Accumulation Ratio of Talazoparib in Combination With Temozolomide
Median with minimum and maximum of the accumulation ratio.
Time frame: Cycle 1 Day 1 pre-dose, and 1, 2, 4 and 8 hours after the first talazoparib dose. Day 5 or 6 pre-dose, and 1, 2, 4 and 8 hours after the talazoparib dose
Half-life of Temozolomide in Combination With Talazoparib
Median with minimum and maximum for the time required for the serum concentration to fall to 50% of its starting dose.
Time frame: Cycle 1 Day 5 or 6 pre-dose, and 1, 2, 4 and 8 hours after the temozolomide dose
T Max of Temozolomide in Combination With Talazoparib
Median with minimum and maximum for the time at which the maximum (peak) serum concentration occurs.
Time frame: Cycle 1 Day 5 or 6 pre-dose, and 1, 2, 4 and 8 hours after the temozolomide dose
C Max of Temozolomide in Combination With Talazoparib
Median with minimum and maximum for the maximum (peak) serum concentration.
Time frame: Cycle 1 Day 5 or 6 pre-dose, and 1, 2, 4 and 8 hours after the temozolomide dose
AUC of Temozolomide in Combination With Talazoparib
Median with minimum and maximum for the area under the drug concentration over time curve.
Time frame: Cycle 1 Day 5 or 6 pre-dose, and 1, 2, 4 and 8 hours after the temozolomide dose.
Clearance of Temozolomide in Combination With Talazoparib
Median with minimum and maximum for the rate of elimination of the drug.
Time frame: Cycle 1 Day 5 or 6 pre-dose, and 1, 2, 4 and 8 hours after the temozolomide dose
Number of Ewing/Peripheral PNET Participants in Phase 2 With Complete Response (CR) or Partial Response (PR)
Frequency of Ewing sarcoma and peripheral PNET participants with Complete Response (CR) or Partial Response (PR) per the Response Evaluation Criteria In Solid Tumors (RECIST)
Time frame: Up to 24 months
Number of Solid Tumor Patients With Complete Response (CR) or Partial Response (PR)
Frequency of solid tumor participants with Complete Response (CR) or Partial Response (PR) per the Response Evaluation Criteria In Solid Tumors (RECIST)
Time frame: Up to 24 months
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