Pamiparib and Temozolomide for the Treatment of Hereditary Leiomyomatosis and Renal Cell Cancer
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|ClinicalTrials.gov Identifier: NCT04603365|
Recruitment Status : Recruiting
First Posted : October 26, 2020
Last Update Posted : October 27, 2021
|Condition or disease||Intervention/treatment||Phase|
|Clear Cell Papillary Renal Neoplasm Collecting Duct Carcinoma Hereditary Leiomyomatosis and Renal Cell Carcinoma Hereditary Papillary Renal Cell Carcinoma Metastatic Renal Cell Carcinoma Metastatic Unclassified Renal Cell Carcinoma Papillary Renal Cell Carcinoma Stage III Renal Cell Cancer American Joint Committee on Cancer (AJCC) v8 Stage IV Renal Cell Cancer AJCC v8 Tubulocystic Renal Cell Carcinoma Unresectable Renal Cell Carcinoma||Drug: Pamiparib Drug: Temozolomide||Phase 2|
I. Evaluate response rate of pamiparib plus low-dose temozolomide.
I. To evaluate the progression-free survival with pamiparib plus low-dose temozolomide.
II. To evaluate the safety (adverse events [AE's]) with pamiparib plus low-dose temozolomide.
I. To determine the association between plasma and tumor 2-hydroxyglutarate (2HG), fumarate, and succinate levels and response to treatment.
II. To analyze the association of the genomic mutational signature (by whole genome sequencing) of the tumor to treatment.
Patients receive orally (PO) twice daily (BID) on days 1-28 and temozolomide PO once daily (QD) on days 1-7. Cycles repeat every 28 days for up to 36 months in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 4 months.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||21 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2 Study of Pamiparib (BGB-290) Plus Temozolomide for Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC)|
|Actual Study Start Date :||October 14, 2021|
|Estimated Primary Completion Date :||August 1, 2023|
|Estimated Study Completion Date :||August 1, 2024|
Experimental: Treatment (pamiparib, temozolomide)
Patients receive PO BID on days 1-28 and temozolomide PO QD on days 1-7. Cycles repeat every 28 days for up to 36 months in the absence of disease progression or unacceptable toxicity.
- Response rate [ Time Frame: Up to 36 months of treatment ]Defined as total number of subjects with confirmed responses of either complete response (CR) or partial response (PR) divided by the total number of subjects in the response-evaluable population per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 by investigator assessment. Response rate will be calculated along with the corresponding exact one-sided 95% Clopper-Pearson confidence interval.
- Progression-free survival (PFS) [ Time Frame: From the first dose of study drug to the date of progressive disease first documented disease progression per RECIST v1.1 or death due to any cause by investigator assessment, whichever occurs first, assessed up to 3 years after completion of treatment ]PFS will be summarized using the Kaplan Meier method as well as descriptively (mean, standard deviation, median, first and third quartiles, minimum, maximum). Figures showing the Kaplan-Meier estimates will also be presented.
- Incidence of adverse events (AEs) [ Time Frame: Up to 36 months ]Safety profile including AE and serious (S)AEs will be reported. Simple descriptive statistics will be used to summarize toxicities in terms of type, severity (by Common Terminology Criteria for Adverse Events [CTCAE] v4.03 toxicity table) and minimum or maximum values for laboratory measures, time of onset, duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects. Adverse events will be tabulated and will include the number of patients for whom the event occurred, the rate of occurrence, and the severity and relationship to study drug.
- Plasma and tumor 2-hydroxyglutarate (2HG), fumarate, and succinate levels [ Time Frame: Up to 36 months ]Plasma and tumor samples will be subjected to multiplex liquid chromatography coupled with tandem mass spectrometry. Will determine the association between plasma and tumor 2HG, fumarate, and succinate levels and response to treatment.
- Genomic mutational signature (by whole genome sequencing) [ Time Frame: Up to 36 months ]Tumor material will be subjected to whole genome sequencing to determine the mutational spectrum. Will analyze the association of the genomic mutational signature of the tumor to treatment.
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): NCT04603365
|Contact: Ankush Sachdeva||310 email@example.com|
|United States, California|
|UCLA / Jonsson Comprehensive Cancer Center||Recruiting|
|Los Angeles, California, United States, 90095|
|Contact: Brian Shuch 310-794-1183 BShuch@mednet.ucla.edu|
|Principal Investigator: Brian Shuch|
|Principal Investigator:||Brian Shuch, MD||UCLA / Jonsson Comprehensive Cancer Center|