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

Anti-Infective Agents

Bevacizumab

Atezolizumab

Antibodies

Antibodies, Monoclonal

Fluorides

Immunoglobulins

Immunoglobulin G

Endothelial Growth Factors

Mitogens

Immunoglobulins, Intravenous

Listerine

Sodium Fluoride

Erlotinib Hydrochloride

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Immunologic Factors

Protective Agents

Immune Checkpoint Inhibitors

Anti-Infective Agents, Local

Patients receive bevacizumab IV over 30-90 minutes and atezolizumab IV over 30-60 minutes on day 1 of each cycle. Patients also receive erlotinib PO QD on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT with or without contrast and MRI throughout the trial. Patients undergo collection of blood throughout the trial, and may undergo a biopsy during screening, as well as a brain MRI/CT scan with contrast, bone scan, and/or F-18 sodium fluoride PET scan as clinically indicated.

Biopsy

Biospecimen Collection

Bone Scan

Computed Tomography

Computed Tomography with Contrast

Erlotinib

Magnetic Resonance Imaging

Positron Emission Tomography

Sodium Fluoride F-18

Site Public Contact

Bassel Nazha

Niraj K. Shenoy

Ramaprasad Srinivasan

Ryan D. Stephenson

Scot A. Niglio

Yuanquan Yang

Risa L. Wong

This phase II trial studies the effects of combination therapy with bevacizumab, erlotinib, and atezolizumab in treating patients with hereditary leiomyomatosis and kidney cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Bevacizumab is in a class of medications called antiangiogenic agents. They work by stopping the formation of blood vessels that bring oxygen and nutrients to tumors. This may slow the growth and spread of tumors. Erlotinib is in a class of medications called kinase inhibitors. It works by blocking the action of a protein called EGFR that signals cancer cells to multiply. This helps slow or stop the spread of cancer cells. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Combination therapy with bevacizumab, erlotinib, and atezolizumab may stabilize or shrink advanced hereditary leiomyomatosis and kidney cancer.

PRIMARY OBJECTIVE:

I. To assess the complete response (CR) rate according to standard Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) in patients with 1) advanced renal cell cancer (RCC) associated with hereditary leiomyomatosis and renal cell cancer (HLRCC) and 2) advanced sporadic/non-HLRCC papillary renal cell cancer treated with a combination of bevacizumab, erlotinib, and atezolizumab.

SECONDARY OBJECTIVES:

I. To determine the safety and tolerability of the combination of bevacizumab, erlotinib, and atezolizumab.

II. To determine the objective response rate (ORR) as complete response (CR) + partial response (PR).

III. To determine disease control rate (DCR) - confirmed response, or stable disease (SD) lasting for at least 6 months.

IV. To assess progression-free survival time (PFS) according to RECIST 1.1. V. To assess overall survival (OS). VI. To assess the duration of response. VII. To assess response to treatment using immune-modified Response Evaluation Criteria in Solid Tumors (iRECIST).

EXPLORATORY OBJECTIVES:

I. To evaluate immunologic modulation associated with the administered treatment regimen, including:

Ia. Peripheral immune subset analysis before and on treatment; Ib. Evaluation of relevant soluble factors before and on treatment. (e.g., cytokine profiles); Ic. Tumor tissue immune infiltration cells before and after treatment (immune microenvironment, CD8/CD4/CD3 cells, T-cell receptor clonality); Id. Evaluation of tissue PDL1/PD1 expression and their correlation with outcome.

II. To assess specific genomic alterations (including fumarate hydratase \[FH\], NRF2 pathway) and determine if there is a correlation with clinical outcomes.

OUTLINE:

Patients receive bevacizumab intravenously (IV) over 30-90 minutes and atezolizumab IV over 30-60 minutes on day 1 of each cycle. Patients also receive erlotinib orally (PO) once daily (QD) on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) with or without contrast and magnetic resonance imaging (MRI) throughout the trial. Patients undergo collection of blood throughout the trial, and may undergo a biopsy during screening, as well as a brain MRI/CT scan with contrast, bone scan, and/or F-18 sodium fluoride positron emission tomography (PET) scan as clinically indicated.

After completion of study treatment, patients are followed up every 6 months.

Testing of Bevacizumab, Erlotinib, and Atezolizumab in Combination for Advanced-Stage Kidney Cancer

A Phase 2 Study of Bevacizumab, Erlotinib and Atezolizumab in Subjects With Advanced Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) Associated or Sporadic Papillary Renal Cell Cancer

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

To determine the safety and tolerability of the combination of bevacizumab, erlotinib, and atezolizumab, the fraction of patients with a dose-limiting toxicity will be reported, along with the maximum grade and type of toxicity for each type noted. Note: In addition to adverse events in the entire study population, pediatric toxicities will also be reported and analyzed separately.

Defined as complete response (CR) + partial response (PR), the fraction with a response (CR+PR) will be reported separately by cohort, along with a 95% confidence interval.

Will be reported for patients with confirmed response, or stable disease (SD) lasting for at least 6 months. Will be reported separately by cohort, along with a 95% confidence interval.

Assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, PFS will be determined using the Kaplan-Meier method, and the curves presented along with a 95% confidence interval on the median PFS, separately by cohort.

The Kaplan-Meier method will be used and the curves presented along with a 95% confidence interval on the median OS, separately by cohort.

The Kaplan-Meier method will be used and the curves presented along with a 95% confidence interval on the median DOR, separately by cohort.

Response to treatment using immune-modified Response Evaluation Criteria in Solid Tumors (iRECIST), the fraction with a response (CR+PR) according to iRECIST will be reported separately by cohort, along with a 95% confidence interval.

National Cancer Institute (NCI)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Pamiparib and Temozolomide for the Treatment of Hereditary Leiomyomatosis and Renal Cell Cancer	NCT04603365	Clear Cell Papi... Collecting Duct... Hereditary Leio... Hereditary Papi... Metastatic Rena... Metastatic Uncl... Papillary Renal... Stage III Renal... Stage IV Renal ... Tubulocystic Re... Unresectable Re...	Pamiparib Temozolomide	18 Years -	Jonsson Comprehensive Cancer Center
Testing of Bevacizumab, Erlotinib, and Atezolizumab in Combination for Advanced-Stage Kidney Cancer	NCT04981509	Hereditary Leio... Papillary Renal... Renal Cell Carc... Sporadic Papill... Stage III Renal... Stage IV Renal ...	Atezolizumab Bevacizumab Biopsy Biospecimen Col... Bone Scan Computed Tomogr... Computed Tomogr... Erlotinib Magnetic Resona... Positron Emissi... Sodium Fluoride...	12 Years -	National Cancer Institute (NCI)

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