Last updated: 11/03/2018 20:44:38
This product has been transferred to Novartis. GSK Clinical Study Register is no longer maintained for this study. The most up to date information is available on clinicaltrials.gov.

A Phase I/II Study to Assess the Safety and Efficacy of Pazopanib and MK 3475 in Subjects with Advanced Renal Cell Carcinoma

GSK study ID
200249
Clinicaltrials.gov ID
NCT02014636
EudraCT ID
2013-003785-14
EU CT Number
Not applicable
Trial status
No longer a GSK study
No longer a GSK study
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

Official title: A Phase I/II Study to Assess the Safety and Efficacy of Pazopanib and MK 3475 in Subjects with Advanced Renal Cell Carcinoma
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Single Group Assignment
Masking:
None (Open Label)
Allocation:
Randomized
Primary outcomes:

Part 1: Change from baseline in laboratory parameters

Timeframe: Average of 4 years

Part 1: Change from baseline in vital signs

Timeframe: 30 days after the last dose of study treatment

Part 2: Progression-free survival (PFS)

Timeframe: Average of 4 years

Part 1: Number of subjects with permanent discontinuation of treatment, dose reductions, interruptions, or delays

Timeframe: 24 months

Part 1: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs )

Timeframe: From the start of study treatment (first dose) and, until the post-treatment follow-up visit (at least 30 days after the last dose of investigational product) for AEs, and until 90 days after last dose for SAEs

Part 1: To determine the dose limiting toxicity (DLT) and maximum tolerated regimen (MTR)

Timeframe: 8 weeks

Part 1: Incidence and titer of anti MK 3475 antibodies

Timeframe: 24 months

Part 1: Change from baseline in cardiac parameters

Timeframe: 24 months

Secondary outcomes:

Part 2: Number of subjects with permanent discontinuation of treatment, dose reductions, interruptions, or delays

Timeframe: Average of 4 years

Part 1 and Part 2: Time to response

Timeframe: Average of 4 years

Part 2: Overall survival (OS) at 18 months

Timeframe: 18 months

Part 2: Change from baseline in vital signs

Timeframe: Average of 4 years

Part 2: Incidence and titer of anti MK 3475 antibodies in patients treated with pazopanib + MK 3475 and single-agent MK 3475

Timeframe: Until 6 months after the last dose of MK-3475

Part 1 and Part 2: Progression-free survival rate at 18 months (PFSR18)

Timeframe: 18 months

Part 2: PFS by modified RECIST

Timeframe: Average of 4 years

Part 1: Dose escalation cohorts: pazopanib plasma concentrations and serum MK 3475 concentrations.

Timeframe: For Pazopanib: before and after the 1st and 2nd dose of MK-3475. For MK-3475: Until 6 months after the last dose of MK-3475

Part 2: PK parameters in randomized phase

Timeframe: For Pazopanib: Until Dose 49 of MK-3475.

Part 1 and Part 2: Clinical benefit rate

Timeframe: Average of 4 years

Part 1 and Part 2: Duration of response

Timeframe: Average of 4 years

Part 2: Overall survival (OS)

Timeframe: Average of 4 years

Part 1: Pharmacokinetic (PK) parameters in Expansion cohort

Timeframe: For Pazopanib: before and after the 1st and 2nd dose of MK-3475. For MK-3475: Until 6 months after the last dose of MK-3475

Part 1 and Part 2: Overall response rate (ORR)

Timeframe: Average of 4 years

Part 2: Change from baseline in laboratory parameters

Timeframe: Average of 4 years

Part 2: Incidence and severity of AEs and SAEs

Timeframe: From the start of study treatment (first dose) and, until the post-treatment follow-up visit (at least 30 days after the last dose of investigational product) for AEs, and until 90 days after last dose for SAEs

Part 2: Change from baseline in cardiac parameters

Timeframe: Average of 4 years

Interventions:
  • Drug: MK-3475
  • Drug: Pazopanib
    • Enrollment:
    228
    Primary completion date:
    2018-17-10
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    Not applicable
    Medical condition
    Carcinoma, Renal Cell
    Product
    GSK3371846, pazopanib
    Collaborators
    Merck
    Study date(s)
    December 2013 to May 2021
    Type
    Interventional
    Phase
    1

    Participation criteria

    Sex
    Female & Male
    Age
    18+ years
    Accepts healthy volunteers
    none
    • 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 (defined as disease not amenable to curative surgery or radiation therapy) or metastatic RCC (equivalent to Stage IV RCC according to American Joint Committee on Cancer [AJCC] staging) that is predominantly clear cell histology. A biopsy containing RCC obtained at anytime from the initial diagnosis to study entry including a recent archival tumor specimen if it is not feasible to obtain a fresh biopsy (a formalin-fixed, paraffin-embedded [FFPE] tumor block is preferred; tissue from a metastatic site is acceptable). The tumor tissue must be submitted no later than 10 days before the start of study treatment.
    • 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.
    Inclusion and exclusion 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 (defined as disease not amenable to curative surgery or radiation therapy) or metastatic RCC (equivalent to Stage IV RCC according to American Joint Committee on Cancer [AJCC] staging) that is predominantly clear cell histology. A biopsy containing RCC obtained at anytime from the initial diagnosis to study entry including a recent archival tumor specimen if it is not feasible to obtain a fresh biopsy (a formalin-fixed, paraffin-embedded [FFPE] tumor block is preferred; tissue from a metastatic site is acceptable). The tumor tissue must be submitted no later than 10 days before the start of study treatment.
    • Must have measurable disease, i.e. presenting with at least one measurable lesion.
    • Subject has received no prior systemic therapy.
    • Male or female >=18 years of age or legal age of consent if greater than 18 years.
    • A woman is eligible to participate in the study if she is of: Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who: Has had a hysterectomy; Has had a bilateral oophorectomy (ovariectomy), Has had a bilateral tubal ligation, Is post-menopausal (total cessation of menses for >=1 year); Childbearing potential, has a negative serum beta-human chorionic gonadotropin (beta HCG) 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 (ECOG PS) 0 or 1.
    • Adequate organ function as defined in the protocol.
    • Left ventricular ejection fraction (LVEF) >= lower limit of normal (LLN) as assessed by echocardiogram (ECHO) or multigated acquisition (MUGA) scan. The same modality used at baseline must be applied for subsequent evaluations.
    • French subjects: 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. Malabsorption syndrome or disease that significantly affects GI function, or major resection of the stomach or small bowel that could affect the absorption of pazopanib.
    • Subject has interstitial lung disease or a history of pneumonitis.
    • Active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, or other Gastrointestinal (GI) 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 human immunodeficiency virus (HIV) infection or a known history of or is positive for Hepatitis B (Hepatitis B surface antigen [HBsAg] reactive) or Hepatitis C (HCV Ribonucleic acid [RNA] [qualitative] is detected).
    • Presence of active infection requiring systemic therapy.
    • Corrected QT interval duration (QTc) prolongation defined as QTc interval >480 milliseconds (msecs).
    • 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 (NYHA) classification.
    • History of cerebrovascular accident within the past 6 months.
    • Poorly controlled hypertension.
    • History of untreated deep venous thrombosis (DVT) (e.g. a calf vein thrombosis that is not treated or pulmonary embolism within the past 6 months). Note: Subjects with recent DVT who are treated with therapeutic anti-coagulating agents (excluding therapeutic warfarin) for at least 2 weeks are eligible.
    • Presence of any non-healing wound, fracture, or ulcer, or presence of symptomatic peripheral vascular disease.
    • Evidence of bleeding diathesis or coagulopathy.
    • Recent hemoptysis (within 8 weeks before first dose of study treatment).
    • Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage, tumor touching but not infiltrating (abutting) the vessels is acceptable (CT with contrast is strongly recommended to evaluate such lesions).
    • 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 (mAb). 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.

    Trial location(s)

    This study does not involve prospective enrollment of participants.

    Study documents

    No study documents available.

    Results overview

    Study Results yet to be posted

    Recruitment status
    No longer a GSK study
    Actual primary completion date
    Not applicable
    Actual study completion date
    Not applicable

    Plain language summaries

    Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

    Additional information about the trial

    Additional information
    Not applicable
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