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

NCT05038839 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2020-0308NCI-2021-03248
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Advanced Malignant Solid Neoplasm; Refractory Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (3)

• Incidence of adverse events

  Will be assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Descriptive statistics will be provided on the grade and type of toxicity by dose level.

  Up to 6 months

• Dose-limiting toxicities

  Up to 28 days

• Recommended phase 2 dosage

  Up to 28 days

Study Arms (1)

Treatment (cabozantinib, pamiparib)

EXPERIMENTAL

Patients receive cabozantinib PO QD and pamiparib PO BID. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Cabozantinib; Drug: Pamiparib

Interventions

Cabozantinib DRUG

Given PO

Treatment (cabozantinib, pamiparib)

Pamiparib DRUG

Given PO

Also known as: BGB-290, PARP Inhibitor BGB-290

Treatment (cabozantinib, pamiparib)

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 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)
• Total bilirubin =\< 1.5 x upper limit of normal (ULN) (upper limit of normal), or total bilirubin \< 3.0 x ULN with direct bilirubin =\< ULN in patients with well documented Gilbert's syndrome (within 14 days before first dose of study treatment)
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (AKP) =\< 3 x ULN. AKP =\< 5 x ULN with documented bone metastases (within 14 days before first dose of study treatment)
• Serum creatinine =\< 1.5 x ULN or calculated creatinine clearance \>= 45 mL/min by the Cockcroft-Gault method (within 14 days before first dose of study treatment)
• Serum albumin \>= 2.8 g/dL (within 14 days before first dose of study treatment)
• Urine protein/creatinine ratio (UPCR) =\< 1 mg/mg (=\< 113.2 mg/mmol), or 24-h urine protein =\< 1 g (within 14 days before first dose of study treatment)

You may not qualify if:

• 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
• Radiation therapy for bone metastasis within 2 weeks or any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible
• Major surgery (e.g., laparoscopic nephrectomy, gastrointestinal (GI) surgery, removal or biopsy of brain metastasis) within 4 weeks before first dose of study treatment. Minor surgeries within 10 days before first dose of study treatment. Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior surgery are not eligible
• 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.
• Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:
• The subject has evidence of tumor invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (e.g., Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction.
• Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose of study treatment.
• Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose of study treatment.
• Other clinically significant disorders that would preclude safe study participation.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Interventions

cabozantinib; pamiparib

Study Officials

• Siqing Fu

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2021
• First Posted: September 9, 2021
• Study Start: February 9, 2022
• Primary Completion (Estimated): June 3, 2026
• Study Completion (Estimated): June 3, 2026
• Last Updated: November 20, 2025

Record last verified: 2025-11

Locations

US (1)