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Talazoparib and Axitinib for People With Previously Treated Advanced Kidney Cancer

Primary Purpose

Kidney Cancer, Renal Cell Carcinoma, Unresectable Renal Cell Carcinoma

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Talazoparib
Axitinib
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Kidney Cancer focused on measuring Kidney Cancer, Advanced Kidney Cancer, Renal Cell Carcinoma, Unresectable Renal Cell Carcinoma, Talazoparib, Axitinib, Metastatic Renal Cell Carcinoma, 20-001, Memorial Sloan Kettering Cancer Center

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Biopsy proven metastatic or unresectable renal cell carcinoma with clear cell component
  • Prior treatment with at least 1 VEGFR TKI and 1 PD-1/PD-L1 immune checkpoint inhibitor (ICI).Combination VEGFR TKI plus ICI will be counted as 1 line of therapy. During the dose escalation portion of the study prior TKI exposure is not required.
  • Dose escalation portion: No maximum prior lines of therapy. Dose expansion portion: maximum of two prior lines of therapy
  • Adequate Hematologic Function

    • Absolute Neutrophil Count ≥ 1.5 x 109 / 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 ≥ 60 ml/min according to the Cockcroft-Gault formula

    ° Patients with moderate renal impairment (creatinine clearance 30-59 ml/min by Cockcroft-Gault) may be eligible in the phase II dose expansion

  • 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 0-2.
  • 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 women, and 4 months for men.
  • Recovery of baseline CTCAE v5.0 grade ≤1 toxicities related to prior study treatments unless adverse events are clinically non-significant per investigator's discretion 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.

Participant Inclusion Criteria for Phase II Dose Expansion

  • Maximum 2 lines of prior therapy. Combination VEGFR TKI plus ICI therapy will be accepted as 1 line of therapy.
  • Adequate Renal Function ≥ 30 ml/min according to the Cockcroft-Gault formula.

    • Patients with normal renal function (Cr clearance ≥ 60 ml/min by Cockcroft-Gault formula) will receive talazoparib at RP2D.
    • Patients with moderate renal impairment (Cr clearance 30-59 ml/min by Cockcroft-Gault formula) will receive talazoparib at one dose level lower than RP2D.

Exclusion Criteria:

  • Prior treatment with talazoparib or other agents which target PARP
  • Prior treatment with axitinib. Other VEGFR TKIs are permissible.
  • 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 study (7 months after last dose of the study treatment for women, and 4 months for men)
  • Prior diagnosis of myelodysplastic syndrome (MDS) or diagnosis of other malignancy that requires anti-cancer directed therapy within the last 12 months. Exclusions include those cancers that are considered cured by local therapy (e.g. 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).
  • 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.
  • Significant vascular disease (i.e. aortic aneurysm requiring surgical repair, recent arterial thrombosis) within 6 months prior to first dose of therapy.
  • Ejection Fraction (EF) ≤50% by echocardiogram (ECHO). Multi-gated acquisition scan (MUGA) should be obtained to estimate EF if quality of ECHO is insufficient.
  • Uncontrolled hypertension defined as systolic blood pressure (BP) ≥160 mmHg or diastolic BP ≥ 100 mmHg despite anti-HTN 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.
  • Active infection requiring parenteral antibiotic therapy.
  • 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 axitinib, or any component in formulations.
  • 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
  • Symptomatic brain metastasis or leptomeningeal disease requiring steroid use. Patients are eligible if they are neurologically stable for 4 weeks, 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
  • Inability to swallow capsules, known intolerance to talazoparib and axitinib or its excipients, known malabsorption syndrome, or other conditions which impair intestinal absorption.

Sites / Locations

  • Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)Recruiting
  • Memorial Sloan Kettering Monmouth (Limited Protocol Activities)Recruiting
  • Memorial Sloan Kettering Bergen (Limited Protocol Activities)Recruiting
  • Memorial Sloan Kettering Cancer Center @ Commack (Limited Protocol Activities)Recruiting
  • Memorial Sloan Kettering Westchester (Limited Protocol Activities)Recruiting
  • Memorial Sloan Kettering Cancer Center (All Protocol Activities)Recruiting
  • Memorial Sloan Kettering Nassau (Limited Protocol Activities)Recruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Phase Ib, Dose Level 1

Phase Ib, Dose Level 2

Phase Ib, Dose Level 3

Phase II, Dose Expansion

Arm Description

3-6 participants

3-6 participants

3-6 participants

Optimal Simon 2-stage Design (14 participants initially, if MTD is tolerated well then accrual will go up to 25 participants)

Outcomes

Primary Outcome Measures

Phase Ib: Recommended dose of talazoparib in combination with standard-dose axitinib
Identify the recommended dose of talazoparib in combination with standard-dose axitinib
Phase Ib: Dose Limiting Toxicity
Dose-limiting toxicity based on adverse events classified according to CTCAE v5.0 observed over 1 cycle of combination talazoparib and axitinib.
Phase II: Objective Response Rate
Evaluate the efficacy as measured by objective response rate (ORR) of combination talazoparib and axitinib in previously treated metastatic clear cell RCC patients.

Secondary Outcome Measures

Full Information

First Posted
April 6, 2020
Last Updated
June 29, 2023
Sponsor
Memorial Sloan Kettering Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT04337970
Brief Title
Talazoparib and Axitinib for People With Previously Treated Advanced Kidney Cancer
Official Title
A Phase Ib/II Study of Talazoparib and Axitinib in Metastatic Renal Cell Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 6, 2020 (Actual)
Primary Completion Date
October 2024 (Anticipated)
Study Completion Date
October 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
Researchers are doing this study to find out if the combination of the drugs axitinib and talazoparib is a safe and effective treatment for people with your previously treated advanced kidney cancer. Researchers will look for the highest dose of talazoparib that causes few or mild side effects when given in combination with a standard dose of axitinib.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Kidney Cancer, Renal Cell Carcinoma, Unresectable Renal Cell Carcinoma, Metastatic Renal Cell Carcinoma
Keywords
Kidney Cancer, Advanced Kidney Cancer, Renal Cell Carcinoma, Unresectable Renal Cell Carcinoma, Talazoparib, Axitinib, Metastatic Renal Cell Carcinoma, 20-001, Memorial Sloan Kettering Cancer Center

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
39 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Phase Ib, Dose Level 1
Arm Type
Experimental
Arm Description
3-6 participants
Arm Title
Phase Ib, Dose Level 2
Arm Type
Experimental
Arm Description
3-6 participants
Arm Title
Phase Ib, Dose Level 3
Arm Type
Experimental
Arm Description
3-6 participants
Arm Title
Phase II, Dose Expansion
Arm Type
Experimental
Arm Description
Optimal Simon 2-stage Design (14 participants initially, if MTD is tolerated well then accrual will go up to 25 participants)
Intervention Type
Drug
Intervention Name(s)
Talazoparib
Intervention Description
Dose Level 1: 0.5 mg PO daily Dose Level 2: 0.75 mg PO daily Dose Level 3: 1 mg PO daily Phase II: MTD to be determined.
Intervention Type
Drug
Intervention Name(s)
Axitinib
Intervention Description
5 mg PO BID
Primary Outcome Measure Information:
Title
Phase Ib: Recommended dose of talazoparib in combination with standard-dose axitinib
Description
Identify the recommended dose of talazoparib in combination with standard-dose axitinib
Time Frame
2 years
Title
Phase Ib: Dose Limiting Toxicity
Description
Dose-limiting toxicity based on adverse events classified according to CTCAE v5.0 observed over 1 cycle of combination talazoparib and axitinib.
Time Frame
28 days
Title
Phase II: Objective Response Rate
Description
Evaluate the efficacy as measured by objective response rate (ORR) of combination talazoparib and axitinib in previously treated metastatic clear cell RCC patients.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Biopsy proven metastatic or unresectable renal cell carcinoma with clear cell component Prior treatment with at least 1 VEGFR TKI and 1 PD-1/PD-L1 immune checkpoint inhibitor (ICI).Combination VEGFR TKI plus ICI will be counted as 1 line of therapy. During the dose escalation portion of the study prior TKI exposure is not required. Dose escalation portion: No maximum prior lines of therapy. Dose expansion portion: maximum of two prior lines of therapy Adequate Hematologic Function Absolute Neutrophil Count ≥ 1.5 x 109 / 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 ≥ 60 ml/min according to the Cockcroft-Gault formula ° Patients with moderate renal impairment (creatinine clearance 30-59 ml/min by Cockcroft-Gault) may be eligible in the phase II dose expansion 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 0-2. 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 women, and 4 months for men. Recovery of baseline CTCAE v5.0 grade ≤1 toxicities related to prior study treatments unless adverse events are clinically non-significant per investigator's discretion 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. Participant Inclusion Criteria for Phase II Dose Expansion Maximum 2 lines of prior therapy. Combination VEGFR TKI plus ICI therapy will be accepted as 1 line of therapy. Adequate Renal Function ≥ 30 ml/min according to the Cockcroft-Gault formula. Patients with normal renal function (Cr clearance ≥ 60 ml/min by Cockcroft-Gault formula) will receive talazoparib at RP2D. Patients with moderate renal impairment (Cr clearance 30-59 ml/min by Cockcroft-Gault formula) will receive talazoparib at one dose level lower than RP2D. Exclusion Criteria: Prior treatment with talazoparib or other agents which target PARP Prior treatment with axitinib. Other VEGFR TKIs are permissible. 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 study (7 months after last dose of the study treatment for women, and 4 months for men) Prior diagnosis of myelodysplastic syndrome (MDS) or diagnosis of other malignancy that requires anti-cancer directed therapy within the last 12 months. Exclusions include those cancers that are considered cured by local therapy (e.g. 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). 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. Significant vascular disease (i.e. aortic aneurysm requiring surgical repair, recent arterial thrombosis) within 6 months prior to first dose of therapy. Ejection Fraction (EF) ≤50% by echocardiogram (ECHO). Multi-gated acquisition scan (MUGA) should be obtained to estimate EF if quality of ECHO is insufficient. Uncontrolled hypertension defined as systolic blood pressure (BP) ≥160 mmHg or diastolic BP ≥ 100 mmHg despite anti-HTN 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. Active infection requiring parenteral antibiotic therapy. 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 axitinib, or any component in formulations. 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 Symptomatic brain metastasis or leptomeningeal disease requiring steroid use. Patients are eligible if they are neurologically stable for 4 weeks, 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 Inability to swallow capsules, known intolerance to talazoparib and axitinib or its excipients, known malabsorption syndrome, or other conditions which impair intestinal absorption.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ritesh Kotecha, MD
Phone
646-422-4839
Email
kotechar@mskcc.org
First Name & Middle Initial & Last Name or Official Title & Degree
Martin Voss, MD
Phone
646-888-4721
Email
vossm@mskcc.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ritesh Kotecha, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
City
Basking Ridge
State/Province
New Jersey
ZIP/Postal Code
07920
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ritesh Kotecha, MD
Phone
646-422-4839
Facility Name
Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
City
Middletown
State/Province
New Jersey
ZIP/Postal Code
07748
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ritesh Kotecha, MD
Phone
646-422-4839
Facility Name
Memorial Sloan Kettering Bergen (Limited Protocol Activities)
City
Montvale
State/Province
New Jersey
ZIP/Postal Code
07645
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ritesh Kotecha, MD
Phone
646-422-4839
Facility Name
Memorial Sloan Kettering Cancer Center @ Commack (Limited Protocol Activities)
City
Commack
State/Province
New York
ZIP/Postal Code
11725
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ritesh Kotecha, MD
Phone
646-422-4839
Facility Name
Memorial Sloan Kettering Westchester (Limited Protocol Activities)
City
Harrison
State/Province
New York
ZIP/Postal Code
10604
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ritesh Kotecha, MD
Phone
646-422-4839
Facility Name
Memorial Sloan Kettering Cancer Center (All Protocol Activities)
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ritesh Kotecha, MD
Phone
646-422-4839
Facility Name
Memorial Sloan Kettering Nassau (Limited Protocol Activities)
City
Uniondale
State/Province
New York
ZIP/Postal Code
11553
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ritesh Kotecha, MD
Phone
646-422-4839

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.
Links:
URL
http://www.mskcc.org
Description
Memorial Sloan Kettering Cancer Center

Learn more about this trial

Talazoparib and Axitinib for People With Previously Treated Advanced Kidney Cancer

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