Testing the Addition of the Anti-Cancer Drug Talazoparib to the Combination of Carboplatin and Paclitaxel for the Treatment of Advanced Cancer

NCT02317874 | Completed Phase 1 DMC

• 4 other identifiers: NCI-2014-02474NCI 97829782UM1CA186716
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 3

Brief Summary

This phase I trial studies the side effects and best dose of talazoparib when given together with carboplatin and paclitaxel in treating patients with solid tumors that have spread to other places in the body (advanced) or cannot be removed by surgery. Talazoparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving talazoparib with carboplatin and paclitaxel may kill more tumor cells.

Conditions

Advanced Malignant Solid Neoplasm; Metastatic Malignant Solid Neoplasm; Unresectable Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose and recommended phase 2 dose of talazoparib three day schedule

  Defined as the highest safely tolerated dose where 0/6 or 1/6 (less than 33%) patients experience a dose-limiting toxicity and two or more patients have experienced a dose-limiting toxicity at the next higher dose level. Adverse events will be evaluated by type and severity using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 until March 31, 2018. CTCAE version 5.0 will be utilized beginning April 1, 2018. Adverse events data collection include adverse event diagnosis, date of onset and resolution, whether the event is ongoing, CTCAE grade, whether the event is serious, frequency, and outcome status, and action taken.

  21 days

• Maximum tolerated dose and recommended phase 2 dose of talazoparib seven day schedule

  Defined as the highest safely tolerated dose where 0/6 or 1/6 (less than 33%) patients experience a dose-limiting toxicity and two or more patients have experienced a dose-limiting toxicity at the next higher dose level. Adverse events will be evaluated by type and severity using the National Cancer Institute CTCAE version 4.0 until March 31, 2018. CTCAE version 5.0 will be utilized beginning April 1, 2018. Adverse events data collection include adverse event diagnosis, date of onset and resolution, whether the event is ongoing, CTCAE grade, whether the event is serious, frequency, and outcome status, and action taken.

  21 days

Secondary Outcomes (3)

• Incidence of toxicity

  Up to 4 weeks after last dose of treatment

• Anti-tumor response

  Up to 4 weeks after last dose of treatment

• Pharmacokinetic parameters (area under the curve and concentration) in plasma samples

  Pre-dose and 4 hours after talazoparib administration on days 1 and 3 or 7 (depending on assigned schedule) of cycle 1 and 0 and 4 hours on day 1 of all subsequent cycles

Other Outcomes (3)

• Maximum concentration levels from plasma samples

  Pre-dose, 2 hours, and 4 hours after talazoparib administration on days 1 and 3 or 7 (depending on assigned schedule) of cycle 1 and day 1 of cycle 1

• Changes in peripheral blood mononuclear cell levels

  Cycle 1 day 1 to cycle 2 day 1

• Changes in mutation status

  Baseline to time of progression (up to 4 weeks after last dose of treatment)

Study Arms (2)

Schedule A (7-day talazoparib, paclitaxel, carboplatin)

EXPERIMENTAL

Patients receive talazoparib PO QD on days 1-7, paclitaxel IV over 1 hour on days 1, 8, and 15, and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. At any time after 4-6 cycles of treatment, patients may continue combination study therapy with talazoparib, carboplatin, and paclitaxel, talazoparib and carboplatin, talazoparib alone (continuous dosing), or observation without therapy at the discretion of the treating physician.

Drug: Carboplatin; Drug: Paclitaxel; Drug: Talazoparib

Schedule B (3-day talazoparib, paclitaxel, carboplatin)

EXPERIMENTAL

Patients receive talazoparib PO QD on days 1-3, paclitaxel IV over 1 hour on days 1, 8, and 15, and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. At any time after 4-6 cycles of treatment, patients may continue combination study therapy with talazoparib, carboplatin, and paclitaxel, talazoparib and carboplatin, talazoparib alone (continuous dosing), or observation without therapy at the discretion of the treating physician.

Drug: Carboplatin; Drug: Paclitaxel; Drug: Talazoparib

Interventions

Carboplatin DRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Schedule A (7-day talazoparib, paclitaxel, carboplatin); Schedule B (3-day talazoparib, paclitaxel, carboplatin)

Paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Schedule A (7-day talazoparib, paclitaxel, carboplatin); Schedule B (3-day talazoparib, paclitaxel, carboplatin)

Talazoparib DRUG

Given PO

Also known as: BMN 673, BMN-673

Schedule A (7-day talazoparib, paclitaxel, carboplatin); Schedule B (3-day talazoparib, paclitaxel, carboplatin)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically confirmed solid malignancy (excluding lymphoma) that is metastatic or unresectable and for which standard curative measures do not exist or are no longer effective, and for which: a) there is reasonable expectation of response to the combination of carboplatin/paclitaxel OR b) BRCA 1/2 germline mutation is present; due to the longstanding acceptance of BRCA 1 and 2 mutation testing through Myriad, results from Myriad will be acceptable; if testing for BRCA 1 and 2 germline mutations is done through another organization, a report from a genetics consult with a qualified medical professional confirming that the laboratory results show a recognized germline deleterious BRCA 1 or 2 mutation or rearrangement is required; if the latter cannot be obtained, principal investigator (PI) or study chair review of the lab results and confirmation of BRCA mutation or rearrangement will be required OR c) BRCA 1/2 somatic mutation previously identified using a Clinical Laboratory Improvement Amendments (CLIA) certified assay
• Patients must have measurable or evaluable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• Life expectancy of greater than 12 weeks
• Absolute neutrophil count \>= 1,500/mcL
• Hemoglobin \>= 9 g/dL
• Platelets \>= 150,000/mcL
• Total bilirubin =\< 1.25 x institutional upper limit of normal (ULN), with the exception of \< 2.9 mg/dL for patients with Gilbert's disease
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x ULN; =\< 5 x ULN in setting of metastatic liver disease
• Creatinine =\< 1.5 x upper limit of normal OR creatinine clearance \>= 50 mL/min
• Ability to take oral medications
• Patients with central nervous system (CNS) metastases must be stable after therapy for CNS metastases (such as surgery, radiotherapy or stereotactic radiosurgery) for at least 4 weeks and must be off steroid treatment for 2 weeks prior to study enrollment
• The effects of talazoparib (BMN 673) on the developing human fetus are unknown; for this reason and because other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of talazoparib (BMN 673) administration
• Ability to understand and the willingness to sign a written informed consent document

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) or targeted therapies within 2 weeks prior to entering the study or those who have not recovered (=\< grade 1) from adverse events due to agents administered with the exception of any grade of alopecia
• No prior carboplatin unless given in neoadjuvant/adjuvant setting for curative intent and more than 6 months have elapsed since last carboplatin dose; in the case of relapsed ovarian cancer, patients are eligible if more than 6 months have elapsed since last carboplatin dose
• Patients who are receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to talazoparib (BMN 673) or other agents used in study
• Peripheral neuropathy of severity greater than grade 1
• The following medications are contraindicated or must be used with caution; because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference
• Contraindicated:
• Cytochrome P450, family 2, subfamily C, polypeptide 8 (CYP2C8) strong and moderate inhibitors
• CYP2C8 inducers
• Cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) strong and moderate inhibitors
• CYP3A4 inducers
• CYP3A4 sensitive substrates
• Transdermal products designed for systemic delivery must be assessed for interaction potential; topical products not designed to provide systemic delivery (including inhaled products, ophthalmologic products and transvaginal preparations) do not need to be considered since they do not have appreciable systemic absorption
• Other contraindicated medications (per above) are not allowed unless close monitoring with labs or drug levels or by symptoms with subsequent dose adjustments is feasible; patients taking these concurrent medications are ineligible unless they can discontinue or switched to alternative medications prior to initiation of the study drug (at least 5 half-lives)
• Use with caution:

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (3)

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

Location

Related Publications (1)

• Leal TA, Sharifi MN, Chan N, Wesolowski R, Turk AA, Bruce JY, O'Regan RM, Eickhoff J, Barroilhet LM, Malhotra J, Mehnert J, Girda E, Wiley E, Schmitz N, Andrews S, Liu G, Wisinski KB. A phase I study of talazoparib (BMN 673) combined with carboplatin and paclitaxel in patients with advanced solid tumors (NCI9782). Cancer Med. 2022 Nov;11(21):3969-3981. doi: 10.1002/cam4.4724. Epub 2022 Apr 8.

  PMID: 35396812 DERIVED

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

Carboplatin; Paclitaxel; Taxes; talazoparib

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations

Study Officials

• Kari B Wisinski

  JHU Sidney Kimmel Comprehensive Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2014
• First Posted: December 17, 2014
• Study Start: September 8, 2015
• Primary Completion: April 1, 2019
• Study Completion: May 3, 2022
• Last Updated: August 29, 2023

Record last verified: 2023-08

Locations

US (3)