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ACTIVE_NOT_RECRUITINGPHASE1

Cabozantinib and Pamiparib for the Treatment of Advanced of Refractory Solid Tumors

A Phase I Study of Cabozantinib and Pamiparib to Evaluate Triple Inhibition of PARP, VEGFR and c-MET in Advanced Homologous Recombination Deficient Malignancies

NCT05038839•M.D. Anderson Cancer Center

View on ClinicalTrials.gov

Summary

This phase I trial finds the best dose and side effects of cabozantinib and pamiparib in treating patients with solid tumors that have spread to other places in the body (advanced) or does not respond to treatment (refractory). Cabozantinib and pamiparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Description

PRIMARY OBJECTIVES: I. To define the maximum tolerated dose (MTD) or maximum administered dose (MAD) and dose-limiting toxic effects (DLTs) of cabozantinib and pamiparib. II. To define the safety profiles of cabozantinib and pamiparib. SECONDARY OBJECTIVES: I. To perform plasma pharmacokinetic analyses of cabozantinib and pamiparib interaction. II. To evaluate patient reported outcomes (PRO). III. To evaluate pre-identified mutations in circulating free deoxyribonucleic acid (DNA) (cfDNA) by next generation sequencing (NGS). IV. To estimate complete responses (CRs), partial responses (PRs), stable disease \>= 6 months (SD \>= 6months), progression free survival (PFS) and overall survival (OS). V. To relate changes in phosphorylated AKT (pAKT), phosphorylated ERK2 (pERK2), phosphorylated c-MET (pc-MET), phosphorylated PARP1 (PARP1-pY907), phosphorylated histone H2A variant H2AX (gamma-H2AX) and RAD51 in tumor specimens with antitumor efficacy. VI. To relate cancer-associated mutations at baseline with antitumor efficacy. VII. To explore potential biomarkers of acquired resistance by comparing molecular signatures at baseline with those at time of relapse in patients in whom SD \>= 6 months/CR/PR or a mixed response are documented, by next-generation deep sequencing or more sophisticated techniques. OUTLINE: This is a dose-escalation study. Patients receive cabozantinib orally (PO) once daily (QD) and pamiparib PO twice daily (BID). Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 6 months.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Patients must have histologically confirmed advanced solid tumors refractory to standard-of-care (SOC) therapy; or no SOC therapy; or declined SOC. During dose expansion, patients have to have one of the following genetic and pathologic features as defined in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory as well:
•* A deleterious BRCA1 or BRCA2 mutation (germline or somatic)
•* A surrogate biomarker for HRD: deleterious mutation or deletion of MRE11, RAD50, NBS1, ATM, ATR, CHEK1, CHEK2, PALB2, ARID1A, Fanconi anemia genes, and PTEN, or loss of PTEN by IHC, amplification of EMSY, etc
•Patients in the dose-escalation phase must have evaluable and/or measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Patients in the dose expansion phase must have measurable disease per RECIST 1.1 and at least one additional lesion that can be biopsied
•Patients age \>= 18 years
•For women of child-bearing potential (women who have not been postmenopausal for at least one year or are not surgically sterile) and all men, agreement to use highly effective contraception (e.g., hormonal contraception, barrier device, or abstinence) prior to study entry for the duration of study participation and for 180 days after the last dose of the study agents. Nonsterile males must avoid sperm donation for the duration of the study and for at least 6 months after the last dose of the study agents
•White blood cell count \>= 2,500/uL, without granulocyte colony-stimulating factor support (within 14 days before first dose of study treatment)
•Absolute neutrophil count (ANC) \>= 1,500/uL, without granulocyte colony-stimulating factor support (within 14 days before first dose of study treatment)
•Hemoglobin \>= 9 g/dL (within 14 days before first dose of study treatment)
•Platelets \>= 100,000/uL, without transfusion (within 14 days before first dose of study treatment)
+12 more criteria

Exclusion Criteria

•Any treatment specifically for systemic tumor control given within 3 weeks before the initiation of the study drugs, within 2 weeks if cytotoxic agents were given weekly, within 4 weeks if cytotoxic agents were given once every 3 to 4 weeks, within 6 weeks for nitrosoureas or mitomycin C, within 5 half-lives for targeted agents with half-lives and pharmacodynamic effects lasting \< 5 days (a minimum of 10 days is required), or failure to recover from toxic effects of any therapy before the initiation of the study drugs
•Unresolved grade 1 or higher toxicity from prior therapy that is clinically significant
•Patient has an inability to swallow oral medications. Note: Patient may not have a percutaneous endoscopic gastrostomy (PEG) tube or be receiving total parenteral nutrition (TPN)
•The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
•* Cardiovascular disorders:
•* Congestive heart failure New York Heart Association class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias.
•* Uncontrolled hypertension defined as sustained blood pressure (BP) \> 140 mm Hg systolic or \> 90 mm Hg diastolic despite optimal antihypertensive treatment.
•* Stroke (including transient ischemic attack \[TIA\]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 6 months before first dose of study treatment.
•* Note: Subjects with a diagnosis of incidental, subsegmental pulmonary embolism (PE) or deep vein thrombosis (DVT) within 6 months are allowed if stable, asymptomatic, and treated with a stable dose of permitted anticoagulation (see exclusion criterion #6) for at least 1 week before first dose of study treatment.
•* Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:
+25 more criteria

Locations (1)

M D Anderson Cancer Center

Houston, Texas, United States

Key Dates

Start Date

February 9, 2022

Primary Completion Date

June 3, 2026

Completion Date

June 3, 2026

Last Updated

November 20, 2025

Enrollment

ESTIMATED participants

Conditions

Advanced Malignant Solid NeoplasmRefractory Malignant Solid Neoplasm

Interventions

Cabozantinib

DRUG

Pamiparib

DRUG

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: November 20, 2025Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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Cabozantinib and Pamiparib for the Treatment of Advanced of Refractory Solid Tumors

Inclusion Criteria

Exclusion Criteria

Measuring the Effects of Talazoparib in Patients With Advanced Cancer and DNA Repair Variations

Testing the Combination of Two Anti-cancer Drugs, DS-8201a and AZD6738, for The Treatment of Advanced Solid Tumors Expressing the HER2 Protein or Gene, The DASH Trial

IACS-6274 With or Without Bevacizumab and Paclitaxel for the Treatment of Advanced Solid Tumors

Testing A New Anti-cancer Drug Combination, Entinostat and ZEN003694, for Advanced and Refractory Solid Tumors

Personalized Antibody-Drug Conjugate Therapy Based on RNA and Protein Testing for the Treatment of Advanced or Metastatic Solid Tumors (The ADC MATCH Screening and Treatment Trial)

Talazoparib and Palbociclib, Axitinib, or Crizotinib for the Treatment of Advanced or Metastatic Solid Tumors, TalaCom Trial