Clinical Trials /

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

NCT03980041

Description:

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.

Related Conditions:
  • Bladder Urothelial Carcinoma
  • Renal Pelvis Urothelial Carcinoma
  • Ureter Urothelial Carcinoma
  • Urethral Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: IPI-549-02
  • NCT ID: NCT03980041

Conditions

  • Bladder Cancer
  • Urothelial Carcinoma
  • Solid Tumor
  • Advanced Cancer

Interventions

DrugSynonymsArms
IPI-549IPI549IPI-549 + Nivolumab
NivolumabOPDIVO®IPI-549 + Nivolumab
PlacebosPlaceboPlacebo + Nivolumab

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
IPI-549 + NivolumabExperimentalParticipants receive IPI-549 orally (PO) daily in combination with nivolumab IV infusion every 4 weeks
  • IPI-549
  • Nivolumab
Placebo + NivolumabActive ComparatorParticipants receive placebo orally (PO) daily in combination with nivolumab IV infusion every 4 weeks
  • Nivolumab
  • Placebos

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate (ORR) per RECISTv1.1
Time Frame:First dosing date to date of confirmed disease progression, assessed up to 24 months
Safety Issue:
Description: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

Measure:Time to Response (TTR)
Time Frame:First dosing date to date of first objective response, assessed up to 24 months
Safety Issue:
Description: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.
Measure:Duration of Response (DOR)
Time Frame:Date of first objective response to date of confirmed disease progression, assessed up to 24 months
Safety Issue:
Description:DOR is defined as the time from the first objective response (CR or PR) to documented disease progression in patients with CR or PR.
Measure:Progression-Free Survival (PFS)
Time Frame:First dosing to date to confirmed disease progression or death, assessed up to 48 months
Safety Issue:
Description:PFS is defined as the time from the first dose of study treatment to documented disease progression or death due to any cause.
Measure: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
Safety Issue:
Description:If TSH result is abnormal, subsequent testing of Free T3 and free T4 required.
Measure:Changes from baseline in electrocardiograms (ECGs)
Time Frame:Screening to date of confirmed disease progression, assessed up to 24 months
Safety Issue:
Description: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.
Measure:Changes from baseline in Eastern Cooperative Oncology Group (ECOG) performance
Time Frame:Screening to date of confirmed disease progression, assessed up to 24 months
Safety Issue:
Description: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).
Measure: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)
Safety Issue:
Description:IPI-549 blood concentrations in ng/mL.
Measure: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)
Safety Issue:
Description:Nivolumab blood concentrations will be assayed in ug/mL.
Measure:Changes from baseline in pulse rate
Time Frame:Screening to date of confirmed disease progression, assessed up to 24 months
Safety Issue:
Description:Pulse rate as measured in beats per minute (bpm)
Measure:Changes from baseline in temperature
Time Frame:Screening to date of confirmed disease progression, assessed up to 24 months
Safety Issue:
Description:Temperature as measured in celsius.
Measure:Changes from baseline in respiration rate
Time Frame:Screening to date of confirmed disease progression, assessed up to 24 months
Safety Issue:
Description:Respiration rate as measured in breaths per minute.
Measure:Changes from baseline in blood pressure
Time Frame:Screening to date of confirmed disease progression, assessed up to 24 months
Safety Issue:
Description:Systolic and diastolic blood pressure as measured in mmHg.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Infinity Pharmaceuticals, Inc.

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