Phase 2
N=40
Talazoparib and Temozolomide in Treating Younger Patients With Refractory or Recurrent Malignancies
Adult Solid Neoplasm · Childhood Solid Neoplasm · Recurrent Childhood Central Nervous System Neoplasm · Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor · Recurrent Malignant Solid Neoplasm
Bottom Line
View on ClinicalTrials.gov: NCT02116777 ↗Enrolled (actual)
40
Serious AEs
85.0%
Results posted
Mar 2021
Primary outcome: Primary: The Number of Participants With Dose Limiting Toxicities to Determine the Maximum Tolerated Dose of Temozolomide and Talazoparib Combination Therapy — 0; 0; 1; 2 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Laboratory Biomarker Analysis (Other); Pharmacological Study (Other); Talazoparib (Drug); Temozolomide (Drug)
- Age
- Pediatric, Adult · 0+ yrs
- Sex
- All
- Sponsor
- National Cancer Institute (NCI)
- Primary completion
- Dec 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY The Number of Participants With Dose Limiting Toxicities to Determine the Maximum Tolerated Dose of Temozolomide and Talazoparib Combination Therapy |
0; 0; 1; 2; 2; 2 | — |
| PRIMARY All Cycle 1 Toxicities >=Grade 3 |
0; 0; 2; 7; 5; 3 | — |
| PRIMARY T Max of Talazoparib |
2 | — |
| PRIMARY C Max of Talazoparib |
4670 | — |
| PRIMARY AUC of Talazoparib |
17.55 | — |
| PRIMARY Accumulation Half-life of Talazoparib in Combination With Temozolomide. |
46.8 | — |
| PRIMARY T Max of Talazoparib in Combination With Temozolomide |
1.04 | — |
| PRIMARY C Max of Talazoparib in Combination With Temozolomide |
16450 | — |
| PRIMARY AUC of Talazoparib in Combination With Temozolomide |
173.08 | — |
| PRIMARY Clearance of Talazoparib in Combination With Temozolomide |
3.08 | — |
| PRIMARY Accumulation Ratio of Talazoparib in Combination With Temozolomide |
3.34 | — |
| PRIMARY Half-life of Temozolomide in Combination With Talazoparib |
1.74 | — |
| PRIMARY T Max of Temozolomide in Combination With Talazoparib |
1.03 | — |
| PRIMARY C Max of Temozolomide in Combination With Talazoparib |
1234.1 | — |
| PRIMARY AUC of Temozolomide in Combination With Talazoparib |
4352.16 | — |
| PRIMARY Clearance of Temozolomide in Combination With Talazoparib |
6.49 | — |
| PRIMARY Number of Ewing/Peripheral PNET Participants in Phase 2 With Complete Response (CR) or Partial Response (PR) |
— | — |
| SECONDARY Number of Solid Tumor Patients With Complete Response (CR) or Partial Response (PR) |
1 | — |
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.
Eligibility Criteria
Inclusion Criteria
- Age:
- Phase 1 (Part A)
- Patients must be > than 12 months and = than 12 months and = = 0.42 m^2 at the time of study enrollment
- Diagnosis:
- Phase 1 (Part A)
- Solid tumors (Part A1): patients with relapsed or refractory solid tumors including central nervous system (CNS) tumors without bone marrow involvement are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse except in patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG)
- Ewing sarcoma or peripheral primitive neuroectodermal tumor (PNET) (Part A2): patients with relapsed or refractory Ewing sarcoma or peripheral PNET without bone marrow involvement will be eligible for Part A2 if there are no available slots on Part A1; these patients will be enrolled at one dose level below the dose level at which patients on Part A1 are actively enrolling, or at the starting dose level (dose level 1) if dose escalation has not yet occurred; patients must have had histologic verification of malignancy at original diagnosis or relapse
- Phase 2 (Part B)
- Ewing sarcoma or peripheral PNET: patients with relapsed or refractory Ewing sarcoma or peripheral PNET are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse
- Phase 2 (Part C)
- Disease status:
- Phase 1 (Part A):
- Patients must have either measurable or evaluable disease
- Phase 2 (Part B):
- Ewing sarcoma or peripheral PNET: patients must have measurable disease
- Therapeutic options: patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
- Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients = = 50% radiation of the pelvis are not eligible
- Stem cell infusion without TBI: no evidence of active graft vs. host disease and at least 84 days must have elapsed after transplant or stem cell infusion
- PARP inhibitor exposure:
- Part A: Patients who have received prior therapy with a PARP inhibitor, with the exception of BMN 673, are eligible; however, patients who have progressed on a PARP inhibitor and temozolomide regimen are not eligible
- Part B: Patients who have previously been exposed to a PARP inhibitor are not eligible
- For patients with solid tumors without known bone marrow involvement: peripheral absolute neutrophil count (ANC) >= 1000/mm^3
- For patients with solid tumors without known bone marrow involvement: platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
- For patients with solid tumors without known bone marrow involvement: hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions)
- All patients enrolled on Part A of the study must be evaluable for hematologic toxicity
- Patients on Part B of the study with known bone marrow metastatic disease will be eligible for the study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity
- Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 or a maximum serum creatinine (mg/dL) based on age/gender as follows:
- 1 to = 16 years: 1.7 for males, 1.4 for females
- Patients on Part A and Part B: bilirubin (sum of conjugated + unconjugated) = = 2 g/dL
- All patients and/or their parents or legally authorized representatives must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines
- For patients enrolling on Part B: tissue blocks or slides must be sent; if tissue blocks or slides
Data sourced from ClinicalTrials.gov (NCT02116777). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.