Cabozantinib and Pamiparib for the Treatment of Advanced of Refractory Solid Tumors
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|ClinicalTrials.gov Identifier: NCT05038839|
Recruitment Status : Not yet recruiting
First Posted : September 9, 2021
Last Update Posted : November 23, 2021
|Condition or disease||Intervention/treatment||Phase|
|Advanced Malignant Solid Neoplasm Refractory Malignant Solid Neoplasm||Drug: Cabozantinib Drug: Pamiparib||Phase 1|
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.
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||44 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Study of Cabozantinib and Pamiparib to Evaluate Triple Inhibition of PARP, VEGFR and c-MET in Advanced Homologous Recombination Deficient Malignancies|
|Estimated Study Start Date :||December 30, 2021|
|Estimated Primary Completion Date :||June 3, 2024|
|Estimated Study Completion Date :||June 3, 2024|
Experimental: Treatment (cabozantinib, pamiparib)
Patients receive cabozantinib PO QD and pamiparib PO BID. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
- Incidence of adverse events [ Time Frame: Up to 6 months ]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.
- Dose-limiting toxicities [ Time Frame: Up to 28 days ]
- Recommended phase 2 dosage [ Time Frame: Up to 28 days ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05038839
|United States, Texas|
|M D Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Contact: Siqing Fu 713-792-4318 firstname.lastname@example.org|
|Principal Investigator: Siqing Fu|
|Principal Investigator:||Siqing Fu||M.D. Anderson Cancer Center|