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Study to Evaluate the Efficacy/Safety of IPI-549 in Combination With Nivolumab in Patients With Advanced Urothelial Carcinoma (MARIO-275)

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ClinicalTrials.gov Identifier: NCT03980041
Recruitment Status : Recruiting
First Posted : June 10, 2019
Last Update Posted : July 30, 2019
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Infinity Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE April 22, 2019
First Posted Date  ICMJE June 10, 2019
Last Update Posted Date July 30, 2019
Actual Study Start Date  ICMJE July 25, 2019
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 6, 2019)
Objective Response Rate (ORR) per RECISTv1.1 [ Time Frame: First dosing date to date of confirmed disease progression, assessed up to 24 months ]
ORR is defined as best response of complete response (CR) or partial response (PR) as measured by RECIST v1.1. RECIST 1.1 = Response Evaluation Criteria in Solid Tumors. CR= Disappearance of all extranodal target lesions. All pathological lymph nodes must have decreased to <10 mm in short axis. PR= At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03980041 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 6, 2019)
  • Time to Response (TTR) [ Time Frame: First dosing date to date of first objective response, assessed up to 24 months ]
    TTR is defined as the time from the first dose of study treatment to first objective response [complete response (CR) or partial response (PR)] in patients with CR or PR.
  • Duration of Response (DOR) [ Time Frame: Date of first objective response to date of confirmed disease progression, assessed up to 24 months ]
    DOR is defined as the time from the first objective response (CR or PR) to documented disease progression in patients with CR or PR.
  • Progression-Free Survival (PFS) [ Time Frame: First dosing to date to confirmed disease progression or death, assessed up to 48 months ]
    PFS is defined as the time from the first dose of study treatment to documented disease progression or death due to any cause.
  • Changes from baseline in thyroid stimulating hormone (TSH) [ Time Frame: Pre-treatment (within 7 days of first dose) to date of confirmed disease progression, assessed up to 24 months ]
    If TSH result is abnormal, subsequent testing of Free T3 and free T4 required.
  • Changes from baseline in electrocardiograms (ECGs) [ Time Frame: Screening to date of confirmed disease progression, assessed up to 24 months ]
    ECGs assess heart problems by measuring the electrical activity generated by the heart as it contracts. The components that will be assessed during the ECG are P wave, QRS complex, ST segment, and T wave.
  • Changes from baseline in Eastern Cooperative Oncology Group (ECOG) performance [ Time Frame: Screening to date of confirmed disease progression, assessed up to 24 months ]
    ECOG performance status describes the level of impact that disease has on the patient's daily living abilities. Scale ranges from 0 (Fully active and able to carry on all pre-disease performance without restriction) to 5 (Dead).
  • Population Pharmacokinetics (PK) of IPI-549-01 [ Time Frame: Pre-dose, 0.5, 1.5, 3 and 6 hours following administration on Day 1 of Cycles 1 and 2 (each cycle is 28 days) ]
    IPI-549 blood concentrations in ng/mL.
  • Pharmacokinetics (PK) of Nivolumab [ Time Frame: Pre-infusion and within 2 minutes of end of infusion on Day 1 of Cycles 1 and 4; Pre-infusion on Day 1 of Cycles 2 and 3, and every 4 cycles starting at Cycle 5 (each cycle is 28 days) ]
    Nivolumab blood concentrations will be assayed in ug/mL.
  • Changes from baseline in pulse rate [ Time Frame: Screening to date of confirmed disease progression, assessed up to 24 months ]
    Pulse rate as measured in beats per minute (bpm)
  • Changes from baseline in temperature [ Time Frame: Screening to date of confirmed disease progression, assessed up to 24 months ]
    Temperature as measured in celsius.
  • Changes from baseline in respiration rate [ Time Frame: Screening to date of confirmed disease progression, assessed up to 24 months ]
    Respiration rate as measured in breaths per minute.
  • Changes from baseline in blood pressure [ Time Frame: Screening to date of confirmed disease progression, assessed up to 24 months ]
    Systolic and diastolic blood pressure as measured in mmHg.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Evaluate the Efficacy/Safety of IPI-549 in Combination With Nivolumab in Patients With Advanced Urothelial Carcinoma (MARIO-275)
Official Title  ICMJE A Phase 2, Multicenter, Randomized, Double-Blind, Active-Control Study to Evaluate the Efficacy and Safety of Nivolumab Administered in Combination With IPI-549 Compared to Nivolumab Monotherapy in the Treatment of Patients With Immune Therapy-Naïve, Advanced Urothelial Carcinoma
Brief Summary The purpose of this study is to measure the effect of IPI-549 in combination with nivolumab when compared to nivolumab monotherapy in advanced urothelial cancer patients.
Detailed Description

Study IPI-549-02 is a multi-national, prospective, randomized, active-control Phase II trial to evaluate the efficacy and safety of IPI 549 administered in combination with nivolumab compared to nivolumab monotherapy.

The study will enroll approximately 160 checkpoint-naïve, advanced urothelial cancer patients who have progressed or recurred following treatment with platinum-based chemotherapy. Patients will be randomized 2:1 to receive intravenous (IV) nivolumab 480 mg every 4 weeks (Q4W) in combination with oral (PO) IPI 549 40 mg once daily (QD) or IV nivolumab 480 mg Q4W in combination with placebo PO QD.

Eligible patients who have confirmed progression of disease during treatment with nivolumab monotherapy may crossover to the combination treatment arm.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Bladder Cancer
  • Urothelial Carcinoma
  • Solid Tumor
  • Advanced Cancer
Intervention  ICMJE
  • Drug: IPI-549
    IPI-549 (40mg QD) administered orally in 28-day cycles
    Other Name: IPI549
  • Drug: Nivolumab
    Nivolumab (480mg Q4W) administered intravenously (IV) in 28-day cycles
    Other Name: OPDIVO®
  • Drug: Placebos
    Placebo administered orally in 28-day cycles
    Other Name: Placebo
Study Arms  ICMJE
  • Experimental: IPI-549 + Nivolumab
    Participants receive IPI-549 orally (PO) daily in combination with nivolumab IV infusion every 4 weeks
    Interventions:
    • Drug: IPI-549
    • Drug: Nivolumab
  • Active Comparator: Placebo + Nivolumab
    Participants receive placebo orally (PO) daily in combination with nivolumab IV infusion every 4 weeks
    Interventions:
    • Drug: Nivolumab
    • Drug: Placebos
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 6, 2019)
160
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 2022
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically or cytologically confirmed urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra
  • Measurable disease by CT or MRI as defined by RECIST v1.1
  • Disease progression or recurrence after treatment:
  • i) With at least 1 platinum-based chemotherapy regimen for the treatment of metastatic (Stage IV) or locally advanced unresectable disease; or
  • ii) With disease recurrence within 1 year of completing a platinum-based neoadjuvant or adjuvant therapy
  • Subject that have received more than 2 prior lines of chemotherapy must not have liver metastases
  • Tumor tissues (archived or new biopsy) must be provided for biomarker analysis
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤1
  • Blood sample must be provided for mMDSC levels for randomization into the study

Exclusion Criteria:

  • Active brain metastases or leptomeningeal metastases
  • Any serious or uncontrolled medical disorder that may interfere with study treatment/interpretation
  • Prior malignancy active within the previous 3 years except for local or organ confined early stage cancer that has been apparently cured
  • Active, known, or suspected autoimmune disease
  • A condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 day of study drug administration
  • Prior therapy with anti-tumor vaccines, any T cell co-stimulation or checkpoint pathways, or IPI-549
  • Prior surgery or gastrointestinal dysfunction that may affect drug absorption
  • Past medical history of interstitial lung disease
  • History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control
  • Positive test for hepatitis B, C or HIV
  • Dependent on continuous supplemental oxygen
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Miriam Brody, MPH 617-453-1142 Miriam.Brody@infi.com
Contact: Jennifer Roberts 617-453-1298 MARIO275@infi.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03980041
Other Study ID Numbers  ICMJE IPI-549-02
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Infinity Pharmaceuticals, Inc.
Study Sponsor  ICMJE Infinity Pharmaceuticals, Inc.
Collaborators  ICMJE Bristol-Myers Squibb
Investigators  ICMJE
Study Director: Samuel Agresta, MD, MPH Infinity Pharmaceuticals, Inc.
PRS Account Infinity Pharmaceuticals, Inc.
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP