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Talazoparib and Avelumab in Participants With Metastatic Renal Cell Carcinoma

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ClinicalTrials.gov Identifier: NCT04068831
Recruitment Status : Recruiting
First Posted : August 26, 2019
Last Update Posted : August 26, 2019
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Brief Summary:
The purpose of this study is to see whether the combination of avelumab and talazoparib can be an effective treatment for metastatic renal cell carcinoma.

Condition or disease Intervention/treatment Phase
Metastatic Renal Cell Carcinoma Advanced Retinal Disease Carcinoma Drug: Talazoparib Drug: Avelumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 44 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description: This is a phase II, open-label, single-institution trial.This is a phase II, open-label, single institution clinical trial of combination talazoparib and avelumab in patients with metastatic RCC. This clinical trial will enroll two separate cohorts in parallel.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Talazoparib and Avelumab in Genomically Defined Metastatic Renal Cell Carcinoma
Actual Study Start Date : August 22, 2019
Estimated Primary Completion Date : August 2022
Estimated Study Completion Date : August 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Avelumab

Arm Intervention/treatment
Experimental: Talazoparib and Avelumab (VHL-deficiency)
All patients will receive combination treatment at the previously established recommended phase II dose, 800 mg avelumab every 2 weeks with 1 mg talazoparib daily, in 28-day cycles.
Drug: Talazoparib
1 mg talazoparib daily

Drug: Avelumab
800 mg avelumab every 2 weeks

Experimental: Talazoparib and Avelumab (FH- or SDH-deficiency)
All patients will receive combination treatment at the previously established recommended phase II dose, 800 mg avelumab every 2 weeks with 1 mg talazoparib daily, in 28-day cycles.
Drug: Talazoparib
1 mg talazoparib daily

Drug: Avelumab
800 mg avelumab every 2 weeks




Primary Outcome Measures :
  1. the objective response rate (ORR) [ Time Frame: 4 months ]
    confirmed complete response (iCR) or partial response (iPR) assessed by iRECIST,



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Biopsy proven, histological confirmed renal cell carcinoma (RCC). Patients with surgery and biopsy at outside institutions will be eligible for this protocol once archival material is reviewed and the above diagnosis confirmed by genitourinary pathology review at Memorial Sloan Kettering Cancer Center (MSKCC).

Cohort 1:

  • Presence of VHL mutation by next-generation sequencing (NGS) with a stateapproved assay
  • Patients must have radiographic evidence of disease progression after treatment with at least one prior PD-1 or PD-L1 agent, and one prior VEGF inhibitor
  • Maximum 3 prior lines of therapy

Cohort 2:

  • FH- or SDH- expression-loss by immunohistochemistry (IHC) or mutation (somatic or germline) in FH or SDH per NGS with a state-approved assay
  • Patients must have radiographic evidence of disease progression after treatment with at least one prior PD-1 or PD-L1 agent, and one prior VEGF inhibitor
  • No maximum lines of therapy

Both Cohorts 1 & 2

  • Adequate Hematologic Function
  • Absolute Neutrophil Count ≥ 1.5 x 10^9 / L
  • Platelet Count ≥ 100 x 10^9 / L
  • Hemoglobin ≥ 9 g/dL
  • No transfusion of packed red blood cells or platelets within 21 days of Cycle 1 Day 1
  • Adequate Renal Function ≥ 30 ml/min according to the Cockcroft-Gault formula
  • Patients with moderate renal impairment (creatinine clearance 30-59 ml/min) will start with a reduced dose of talazoparib.
  • Adequate Hepatic Function including:
  • Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
  • AST ≤ 3 x upper limit of normal (ULN) without liver metastasis
  • ALT ≤ 3 x upper limit of normal (ULN) without liver metastasis
  • AST or ALT ≤ 5 x upper limit of normal (ULN) for patients with liver metastasis
  • Patients with known Gilbert's syndrome may be included if total bilirubin ≤ x 3 ULN
  • Eastern Cooperative Group (ECOG) Performance Status 0-1.
  • Patients must have measurable disease by RECIST v1.1. At least one measurable lesion should not have been previously irradiated.
  • Women of childbearing potential must have negative urine or serum pregnancy testing at screening. All women will be considered childbearing potential unless meeting criteria including:
  • Achieved post-menopausal status as defined by cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause and have follicular stimulation hormone showing postmenopausal state. Women who have been amenorrhoeic for ≥12 months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, anorexia, low body weight, ovarian suppression, anti-estrogen therapy or other medically inducible reasons.
  • Documented hysterectomy or bilateral oophorectomy surgery
  • Medically confirmed ovarian failure
  • Sexually active participants and their partners must agree to use medically accepted methods of contraception (i.e. barrier methods including condoms, female condom, or diaphragm with spermicidal gel) during the study and for 7 months after the last dose of the study treatment for females, and 4 months for males.
  • Recovery of baseline CTCAE v5.0 grade ≤1 toxicities related to prior study treatments unless adverse events are clinically non-significant and/or stable on supportive therapy if needed.
  • Patients must be willing and able to comply with trial protocol. This includes adhering to the treatment plan, scheduled visits, laboratory and other study procedures.

Exclusion Criteria:

  • Patients < 18 years old
  • Patients who are pregnant or breast-feeding. Fertile patients who are unwilling or unable to use two methods of contraception (at least one of which considered highly effective) for duration of study and after 5 months after last dose of study treatment for female, and 7 months for males.
  • Patients who had prior immune checkpoint blockade therapy (either anti-PD-1, anti- PD-L1 and/or anti-CTLA-4) discontinued due to development of an immune related adverse event.
  • Prior diagnosis of myelodysplastic syndrome (MDS) or diagnosis of other malignancy that requires anti-cancer directed therapy within the last 24 months. Exclusions include those cancers that are considered cured by local therapy (i.e.Basal cell carcinoma, squamous cell carcinoma, ducal carcinoma in situ of breast, bladder of cervix) or other cancers that have low malignant potential and do not require systemic therapy (i.e. Gleason-grade <6 prostate adenocarcinoma, borderline ovarian malignancy / low malignant potential).
  • Prior treatment with talazoparib or other agents that target PARP
  • Treatment with anti-cancer therapies within 21 days or five half-lives, whichever shorter, of start date, including monoclonal antibody, cytotoxic therapy, or another investigational agent. There is no specific time window between last PD-1/PD-L1 therapy and start date of new therapy on protocol.
  • Significant vascular disease (i.e. aortic aneurysm requiring surgical repair, recent arterial thrombosis) within 6 months prior to first dose of therapy.
  • Evidence of bleeding diathesis or significant unexplained coagulopathy (i.e. absent of anticoagulation)
  • Clinical signs or symptoms of gastrointestinal obstruction requirement parenteral hydration, parenteral nutrition, or feeding tube.
  • Uncontrolled effusion management (pleural effusion, pericardial effusion, or ascites) which requires recurrent drainage procedures.
  • Patients treated with systemic immunosuppressants; except for

    1. chronic physiologic replacement of ≤ 10mg prednisone (or equivalent) for treatment of adrenal insufficiency; Steroids required for pre-medication reactions
    2. Local steroid use is permitted (e.g. intranasal, topical, inhaled, or local steroid injection, i.e. intra-articular)
  • Patients with autoimmune disease that may worsen during immune checkpoint blockade therapy are excluded. Patients with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requirement immunosuppressive treatment as above are eligible.
  • Prior organ transplantation including allogeneic stem cell transplant.
  • No active infection requiring parenteral antibiotic therapy.
  • Prior diagnosis of HIV/AIDS
  • History of either positive HCV RNA viral load or anti-HCV antibody screening detectable; HBV infection with HBV surface antigen detection and/or positive HBV DNA viral load.
  • Known hypersensitivity to talazoparib or avelumab, or any component in formulations. Patients with known hypersensitivity to monoclonal antibodies (Grade ≥3 by CTCAE v5.0)
  • Live vaccination within 4 weeks of first dose of therapy. All vaccines except inactivated are prohibited while on study.
  • Severe acute or chronic medical conditions which may significantly increase the risk of study participants, per treating investigator's discretion
  • Radiation therapy to any site (including bone) <2 weeks prior to the first dose of therapy. Patients with clinically relevant ongoing complications from prior radiation therapy, per investigators' assessment, are not eligible.
  • Symptomatic brain metastasis or leptomeningeal disease requiring steroid use. Patients are eligible if they neurologically stable for 4 weeks, and have completed radiation therapy or surgery, and recovered from side effects. Patients must have discontinued steroid therapy for at least 2 weeks prior to first dose of study treatment.
  • Current or anticipated use of potent P-gp inhibitors within 7 days prior to randomization or anticipated use during the study. Please see Appendix 5 for a list of potent P-gp inhibitors.
  • Inability to swallow capsules, known intolerance to talazoparib or its excipients, known malabsorption syndrome, or other conditions which impair intestinal absorption.
  • Investigator site staff members directly involved in study conduct, including but not limited to their family members, or patients who are Pfizer members, including their family members, who are directly involved in study conduct.

Information from the National Library of Medicine

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): NCT04068831


Contacts
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Contact: Martin Voss, MD 646-888-4721 vossm@mskcc.org
Contact: Robert Motzer, MD 646-888-4722

Locations
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United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Martin Voss, MD    646-888-4721      
Contact: Robert Motzer, MD    646-888-4722      
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Investigators
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Principal Investigator: Martin Voss, MD Memorial Sloan Kettering Cancer Center

Additional Information:
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Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT04068831     History of Changes
Other Study ID Numbers: 19-195
First Posted: August 26, 2019    Key Record Dates
Last Update Posted: August 26, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
Supporting Materials: Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Memorial Sloan Kettering Cancer Center:
Talazoparib
Avelumab
19-195
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Renal Cell
Retinal Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Eye Diseases
Talazoparib
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents