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

NCT04603365 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: 20-001106NCI-2020-05351
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Response rate

  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.

  Up to 36 months of treatment

Secondary Outcomes (2)

• Progression-free survival (PFS)

  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

• Incidence of adverse events (AEs)

  Up to 36 months

Other Outcomes (2)

• Plasma and tumor 2-hydroxyglutarate (2HG), fumarate, and succinate levels

  Up to 36 months

• Genomic mutational signature (by whole genome sequencing)

  Up to 36 months

Study Arms (1)

Treatment (pamiparib, temozolomide)

EXPERIMENTAL

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.

Drug: Pamiparib; Drug: Temozolomide

Interventions

Pamiparib DRUG

Given PO

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

Treatment (pamiparib, temozolomide)

Temozolomide DRUG

Given PO

Also known as: CCRG-81045, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831, M and B 39831, Methazolastone, RP-46161, SCH 52365, Temcad, Temodal, Temodar, Temomedac, TMZ

Treatment (pamiparib, temozolomide)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject has voluntarily agreed to participate by signing an informed consent
• Eastern Cooperative Oncology Group (ECOG) performance status of =\< 1
• Ability to swallow whole capsules
• Histologically confirmed metastatic or unresectable renal cell carcinoma with morphologic features consistent with hereditary leiomyomatosis and renal cell cancer (HLRCC). This can include tumors with overlapping morphology previously called papillary, tubulocystic, tubulopapillary, collecting duct, or unclassified as long as in the HLRCC- spectrum
• The presence of a documented germline fumarate hydratase (FH) alteration (mutation or deletion). This includes pathogenic or likely pathogenic alterations but may also include variants of unknown significance (VUS) in patients with strong personal or family history where the clinician makes a presumed clinical diagnosis
• Progression on 1 or more lines of systemic therapies for metastatic disease. Neo/adjuvant therapy in the absence of documented distant disease does not count as a line of therapy
• No known intolerance of study drugs or excipients, and able to comply with study requirements
• Absolute neutrophil count (ANC) \>= 1,500 /microliter (mcL) (\< 2 weeks prior to day 1)
• Platelets \>= 100,000 / mcL (\< 2 weeks prior to day 1)
• Hemoglobin \>= 10 g/dL or \>= 6.2 mmol/L without transfusion or erythropoietin (EPO) dependency (within 2 weeks of first dose)
• Serum creatinine =\< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]) \>= 40 mL/min for participants with creatinine levels \> 1.5 x institutional ULN (\< 2 weeks prior to day 1)
• Creatinine clearance should be calculated using the standard Cockcroft and Gault equation
• Total serum bilirubin =\< 1.5 x ULN (total bilirubin must be \< 4 x ULN for subject with Gilbert's syndrome) (\< 2 weeks prior to day 1)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =\< 3 x ULN OR =\< 5 x ULN for participants with liver metastases (\< 2 weeks prior to day 1)
• International normalized ratio (INR) or prothrombin time (PT), and activated partial thromboplastin time (aPTT) =\<1.5 x ULN unless participant is receiving anticoagulant therapy, and then only as long as PT or PTT is within therapeutic range of intended use of anticoagulants (\< 2 weeks prior to day 1)

You may not qualify if:

• Known hypersensitivity to any temozolomide (TMZ) component
• Prior treatment with a PARP inhibitor
• Received chemotherapy, biologic therapy, immunotherapy, or investigational agent within 3 weeks (or =\< 5 half-lives, whichever is shorter) prior to cycle 1/day 1
• Have any unresolved acute effects of any prior therapy of grade 2 or higher, except for AEs not constituting a safety risk by investigator judgment
• Had a major surgical procedure (per investigator discretion) =\< 4 weeks prior to cycle 1/day 1, or anticipation of need for major surgical procedure during the course of the study
• Have other diagnosis of malignancy
• Except for surgically excised non-melanoma skin cancer, adequately treated carcinoma in situ of the cervix, localized prostate cancer treated with curative intent, adequately treated low-stage bladder cancer, ductal carcinoma in situ treated surgically with curative intent, or a malignancy diagnosed \> 2 years ago, with no current evidence of disease and no therapy =\< 2 years prior to day 1
• Subject who has received local radiotherapy of non-target lesions for local symptom control within the last 4 weeks must have recovered from any adverse effects of radiotherapy before recording baseline symptoms
• Have untreated leptomeningeal or brain metastasis. Subject with previously treated brain metastases is eligible if the metastases have shown no progression on brain computed tomography (CT) or magnetic resonance imaging (MRI) over at least 4 weeks, the subject has no symptoms due to the brain metastases, and the subject has been off corticosteroids for \>= 2 weeks
• Have active infection requiring systemic treatment
• Have known human immunodeficiency virus (HIV) infection
• No known chronic active liver disease or evidence of acute or chronic hepatitis B virus (HBV) or hepatitis C (HCV) infection. Patients with prior curative treatment of hepatitis C virus are allowed if treated \> 2 weeks prior to treatment previously and HCV ribonucleic acid (RNA) undetectable by established laboratory values
• Have any of the following cardiovascular criteria:
• Current evidence of cardiac ischemia
• Current symptomatic pulmonary embolism

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• BeiGene: collaborator
• Driven To Cure: collaborator

MeSH Terms

Conditions

Carcinoma, Renal Cell; Hereditary leiomyomatosis and renal cell cancer

Interventions

pamiparib; Temozolomide

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Brian Shuch, MD

  UCLA / Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2020
• First Posted: October 26, 2020
• Study Start: October 18, 2021
• Primary Completion: May 7, 2023
• Study Completion: May 7, 2023
• Last Updated: May 17, 2023

Record last verified: 2022-10