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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.

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.

Condition or disease Intervention/treatment Phase
Bladder Cancer Urothelial Carcinoma Solid Tumor Advanced Cancer Drug: IPI-549 Drug: Nivolumab Drug: Placebos Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : July 25, 2019
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : November 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Nivolumab

Arm Intervention/treatment
Experimental: IPI-549 + Nivolumab
Participants receive IPI-549 orally (PO) daily in combination with nivolumab IV infusion every 4 weeks
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®

Active Comparator: Placebo + Nivolumab
Participants receive placebo orally (PO) daily in combination with nivolumab IV infusion every 4 weeks
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




Primary Outcome Measures :
  1. 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.



Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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).

  7. 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.

  8. 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.

  9. 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)

  10. Changes from baseline in temperature [ Time Frame: Screening to date of confirmed disease progression, assessed up to 24 months ]
    Temperature as measured in celsius.

  11. 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.

  12. 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.



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:

  • 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

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): NCT03980041


Contacts
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Contact: Miriam Brody, MPH 617-453-1142 Miriam.Brody@infi.com
Contact: Jennifer Roberts 617-453-1298 MARIO275@infi.com

Locations
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United States, Minnesota
Coborn Cancer Center Recruiting
Saint Cloud, Minnesota, United States, 56303
Contact: Donald Jurgens, Dr.         
Sponsors and Collaborators
Infinity Pharmaceuticals, Inc.
Bristol-Myers Squibb
Investigators
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Study Director: Samuel Agresta, MD, MPH Infinity Pharmaceuticals, Inc.

Additional Information:
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Responsible Party: Infinity Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT03980041     History of Changes
Other Study ID Numbers: IPI-549-02
First Posted: June 10, 2019    Key Record Dates
Last Update Posted: July 30, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Nivolumab
Antineoplastic Agents, Immunological
Antineoplastic Agents