Talazoparib and Temozolomide in Treating Younger Patients With Refractory or Recurrent Malignancies
A Phase 1/2 Study of BMN 673, an Oral Poly(ADP-Ribose) Polymerase Inhibitor, Plus Temozolomide in Children With Refractory or Recurrent Malignancies
3 other identifiers
interventional
40
1 country
22
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started May 2014
Longer than P75 for phase_1
22 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 15, 2014
CompletedFirst Posted
Study publicly available on registry
April 17, 2014
CompletedStudy Start
First participant enrolled
May 16, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
December 31, 2018
CompletedResults Posted
Study results publicly available
March 26, 2021
CompletedMarch 26, 2021
March 1, 2021
4.6 years
April 15, 2014
February 12, 2020
March 1, 2021
Conditions
Outcome Measures
Primary Outcomes (17)
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.
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
Up to 28 days
T Max of Talazoparib
Median with minimum and maximum for the time at which the maximum (peak) serum concentration occurs.
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.
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.
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.
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.
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.
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
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.
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.
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.
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.
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.
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.
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.
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)
Up to 24 months
Secondary Outcomes (1)
Number of Solid Tumor Patients With Complete Response (CR) or Partial Response (PR)
Up to 24 months
Study Arms (2)
Treatment (talazoparib, temozolomide): Phase 1
EXPERIMENTAL(Part A): Patients receive talazoparib PO QD or 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.
Treatment (talazoparib, temozolomide): Phase 2
EXPERIMENTAL(Part B): Relapse/Refractory EWS or PNET Patients receive MTD from Phase 1 portion of study. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
Interventions
Correlative studies
Correlative studies
Given PO
Given PO
Eligibility Criteria
You may qualify if:
- Age:
- Phase 1 (Part A)
- Patients must be \> than 12 months and =\< 21 years of age at the time of study enrollment
- Phase 2 (Part B)
- Patients must be \> than 12 months and =\< 30 years of age at the time of study enrollment
- Body surface area (for Parts A and B):
- Patients must have a body surface area (BSA) of \>= 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:
- +36 more criteria
You may not qualify if:
- Pregnant or breast-feeding women will not be entered on this study; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
- Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible
- Patients who are currently receiving another investigational drug are not eligible
- Patients who are currently receiving other anti-cancer agents are not eligible (except leukemia patients receiving hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy); patients with acute lymphoblastic leukemia may receive intrathecal therapy
- Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
- Patients must be able to swallow capsules whole
- Patients who have an uncontrolled infection are not eligible
- Patients who have received a prior solid organ transplantation are not eligible
- Patients with prior TBI, craniospinal XRT and/or those with \>= 50% radiation of the pelvis are not eligible
- Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
- Patients with known hypersensitivity to temozolomide or dacarbazine are not eligible
- Phase 1 (Part A): patients who have progressed on a PARP inhibitor and temozolomide regimen are not eligible
- Phase 2 (Part B): patients who have previously been exposed to a PARP inhibitor are not eligible
- Phase 1 (Part A): patients with known bone marrow involvement are not eligible
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (22)
Children's Hospital of Alabama
Birmingham, Alabama, 35233, United States
Children's Hospital Los Angeles
Los Angeles, California, 90027, United States
Children's Hospital of Orange County
Orange, California, 92868, United States
UCSF Medical Center-Parnassus
San Francisco, California, 94143, United States
UCSF Medical Center-Mission Bay
San Francisco, California, 94158, United States
Children's Hospital Colorado
Aurora, Colorado, 80045, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, 30322, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611, United States
Riley Hospital for Children
Indianapolis, Indiana, 46202, United States
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109, United States
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224, United States
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030, United States
Seattle Children's Hospital
Seattle, Washington, 98105, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Related Publications (1)
Schafer ES, Rau RE, Berg SL, Liu X, Minard CG, Bishop AJR, Romero JC, Hicks MJ, Nelson MD Jr, Voss S, Reid JM, Fox E, Weigel BJ, Blaney SM. Phase 1/2 trial of talazoparib in combination with temozolomide in children and adolescents with refractory/recurrent solid tumors including Ewing sarcoma: A Children's Oncology Group Phase 1 Consortium study (ADVL1411). Pediatr Blood Cancer. 2020 Feb;67(2):e28073. doi: 10.1002/pbc.28073. Epub 2019 Nov 14.
PMID: 31724813DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Results Reporting Coordinator
- Organization
- Children's Oncology Group
Study Officials
- PRINCIPAL INVESTIGATOR
Eric S Schafer
COG Phase I Consortium
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 15, 2014
First Posted
April 17, 2014
Study Start
May 16, 2014
Primary Completion
December 31, 2018
Study Completion
December 31, 2018
Last Updated
March 26, 2021
Results First Posted
March 26, 2021
Record last verified: 2021-03