Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Skin and Connective Tissue Diseases

Rare Diseases

Carcinoma

Carcinoma, Renal Cell

Carcinoma, Ductal

Kidney Neoplasms

Leiomyomatosis

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Leiomyoma

Myofibroma

Neoplasms, Connective and Soft Tissue

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Papillary Renal Cell Carcinoma

Chromophil Renal Cell Carcinoma

Collecting Duct Carcinoma

Hereditary Leiomyomatosis and Renal Cell Cancer

Antineoplastic Agents

All Drugs and Chemicals

Temozolomide

Pamiparib

Poly(ADP-ribose) Polymerase Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Enzyme Inhibitors

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.

Brian Shuch, MD

This phase II trial investigates how well pamiparib and temozolomide work in treating patients with hereditary leiomyomatosis and renal cell (kidney) cancer. Poly adenosine diphosphate-ribose polymerase (PARPs) are proteins that help repair DNA mutations. PARP inhibitors, such as pamiparib, can keep PARP from working, so tumor cells can't repair themselves, and they may stop growing. Chemotherapy drugs, such as temozolomide, 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 pamiparib and temozolomide may help treat patients with hereditary leiomyomatosis and renal cell cancer.

PRIMARY OBJECTIVE:

I. Evaluate response rate of pamiparib plus low-dose temozolomide.

SECONDARY OBJECTIVES:

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.

TRANSLATIONAL OBJECTIVES:

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.

OUTLINE:

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.

Pamiparib and Temozolomide for the Treatment of Hereditary Leiomyomatosis and Renal Cell Cancer

A Phase 2 Study of Pamiparib (BGB-290) Plus Temozolomide for Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC)

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.

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.

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.

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.

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.

BeiGene

Driven To Cure

Jonsson Comprehensive Cancer Center

Spots Global Cancer Trial Database for clear cell papillary renal neoplasm