Safety and Efficacy Study of Pazopanib and MK 3475 in Advanced Renal Cell Carcinoma (RCC; KEYNOTE-018)

NCT ID: NCT02014636

Last Updated: 2020-03-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-12-27
• Study Completion Date: 2019-02-27

Brief Summary

This is an open-label, 2 part study of pazopanib and/or MK 3475 in treatment naïve subjects with advanced RCC. Part 1 consists of a Phase I dose escalation of pazopanib + MK 3475 followed by an expansion cohort to determine the maximum tolerated regimen and the recommended Phase II dose. Part 2 is a randomized 3-arm Phase II study to evaluate the clinical efficacy and safety of pazopanib + MK 3475 as compared to single-agent pazopanib and single-agent MK 3475. The objectives of this Phase I/II study are to test the safety and tolerability of pazopanib in combination with MK 3475, and study the clinical efficacy of pazopanib in combination with MK 3475 in subjects with advanced RCC as compared with single-agent pazopanib and single-agent MK 3475.

Following the Urgent Safety Measure (USM) released on February 09, 2017, the phase II (Part 2) portion of this study will not commence.

Conditions

Carcinoma, Renal Cell

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1

Part 1 is a dose escalation phase in which subjects will receive pazopanib orally and the MK 3475 intravenously. Subjects will be evaluated for a minimum of 8 weeks before the next dose level cohort is enrolled.

Group Type: EXPERIMENTAL

Pazopanib

Intervention Type: DRUG

Pazopanib is an orally administered 200 mg tablet available in the dose range of 400 to 800 mg

MK-3475

Intervention Type: DRUG

MK 3475 is an intravenously administered 100 mg/ 4mL solution available in the potential dose range of 1 to 10 mg/kg.

Part 2

Part 2 is a randomized phase in which subjects will be enrolled in each treatment arm:

Pazopanib monotherapy Pazopanib+MK-3475 MK-3475 monotherapy

Group Type: EXPERIMENTAL

Pazopanib

Intervention Type: DRUG

Pazopanib is an orally administered 200 mg tablet available in the dose range of 400 to 800 mg

MK-3475

Intervention Type: DRUG

MK 3475 is an intravenously administered 100 mg/ 4mL solution available in the potential dose range of 1 to 10 mg/kg.

Interventions

Pazopanib

Pazopanib is an orally administered 200 mg tablet available in the dose range of 400 to 800 mg

Intervention Type: DRUG

MK-3475

MK 3475 is an intravenously administered 100 mg/ 4mL solution available in the potential dose range of 1 to 10 mg/kg.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Signed written informed consent before performance of study-specific procedures or assessments and must be willing to comply with treatment and follow up
• Diagnosis of locally advanced or metastatic RCC that is predominantly clear cell histology
• Must have measurable disease
• Subject has received no prior systemic therapy
• A woman is eligible to participate in the study if she is of Non-childbearing potential, has a negative serum pregnancy test within 7 days of the first dose of study treatment, not lactating, and agrees to use adequate contraception during the study until at least 120 days after the last dose of investigational product
• Eastern Cooperative Oncology Group performance status 0 or 1
• Adequate organ function as defined in the protocol
• Left ventricular ejection fraction >= lower limit of normal as assessed by echocardiogram or multigated acquisition scan
• In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category

Exclusion Criteria

• Subject has an active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents
• Subject is currently participating or has participated in a study of an investigational agent or using an investigational device within 30 days of the first dose of study treatment
• Subject is expected to require any other form of systemic or localized antineoplastic therapy while on study
• Subject is on any systemic steroid therapy, within one week before the planned date for first dose of study treatment. Subject is on any other form of immunosuppressive medication
• Subject has a history of a malignancy (other than the disease under treatment in the study) within 5 years before first study treatment administration
• Central nervous system metastasis
• Unable to swallow and retain orally administered medication
• Subject has interstitial lung disease or a history of pneumonitis
• Active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, or other Gastrointestinal conditions with increased risk of perforation; history of abdominal fistula, GI perforation, or intra-abdominal abscess within 4 weeks before beginning study treatment
• Known history of HIV infection or a known history of or is positive for Hepatitis B or Hepatitis C
• Presence of active infection requiring systemic therapy
• Corrected QT interval duration prolongation
• History of any one or more of the following cardiac conditions within the past 6 months: Cardiac angioplasty or stenting; Myocardial infarction; Unstable angina; History of Class III or IV congestive heart failure according to New York Heart Association classification
• History of cerebrovascular accident within the past 6 months
• Poorly controlled hypertension
• History of untreated deep venous thrombosis
• Presence of any non-healing wound, fracture, or ulcer, or presence of symptomatic peripheral vascular disease
• Evidence of bleeding diathesis or coagulopathy
• Recent hemoptysis
• Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage
• Any serious and/or unstable pre-existing medical, psychiatric, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures
• Previous severe hypersensitivity reaction to another Monoclonal antibody. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the excipients in pazopanib tablets
• Has taken any prohibited medications that are listed in the protocol within 14 days of the first dose of study treatment. Subject has received or will receive a live vaccine within 30 days before the first administration of study treatment

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Boston, Massachusetts, United States

Novartis Investigative Site

Boston, Massachusetts, United States

Novartis Investigative Site

New York, New York, United States

Novartis Investigative Site

Nashville, Tennessee, United States

Novartis Investigative Site

Manchester, Lancashire, United Kingdom

Novartis Investigative Site

London, , United Kingdom

Countries

United States; United Kingdom

Other Identifiers

KEYNOTE-018

Identifier Type: OTHER

Identifier Source: secondary_id

PZP034A2101

Identifier Type: OTHER

Identifier Source: secondary_id

200249

Identifier Type: -

Identifier Source: org_study_id