Clinical Trials /

Study of Sacituzumab Govitecan (IMMU-132) in Metastatic or Locally Advanced Unresectable Urothelial Cancer

NCT04527991

Description:

This is a Phase III, global, multicenter, open-label randomized controlled trial in patients with metastatic or locally advanced unresectable urothelial cancer who have progressed after prior therapy with platinum-based regimen and anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) therapy. Approximately 600 subjects from 123 global sites will be enrolled

Related Conditions:
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Study of Sacituzumab Govitecan (IMMU-132) in Metastatic or Locally Advanced Unresectable Urothelial Cancer
  • Official Title: A Randomized Open-Label Phase III Study of Sacituzumab Govitecan Versus Treatment of Physician's Choice in Subjects With Metastatic or Locally Advanced Unresectable Urothelial Cancer (TROPiCS-04)

Clinical Trial IDs

  • ORG STUDY ID: IMMU-132-13
  • NCT ID: NCT04527991

Conditions

  • Urothelial Carcinoma
  • Bladder Cancer
  • Metastatic Urothelial Carcinoma
  • Locally Advanced Urothelial Cancer
  • Transitional Cell Carcinoma

Interventions

DrugSynonymsArms
sacituzumab govitecan 10 mg/kg IV q21 day dosingIMMU-132sacituzumab govitecan
Treatment of Physician's Choice of either paclitaxel 175 mg/m2, docetaxel 75 mg/m2 or vinflunine 320 mg/m2Treatment of Physician's Choice

Purpose

This is a Phase III, global, multicenter, open-label randomized controlled trial in patients with metastatic or locally advanced unresectable urothelial cancer who have progressed after prior therapy with platinum-based regimen and anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) therapy. Approximately 600 subjects from 123 global sites will be enrolled

Detailed Description

      This is a Phase III, global, multicenter, open-label randomized controlled trial in which
      approximately 600 subjects with metastatic or locally advanced unresectable UC who have
      progressed after prior therapy with platinum-based regimen and anti-programmed cell death
      protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) therapy will be randomized to either
      sacituzumab govitecan arm or Treatment of Physician's Choice (TPC) arm.

      Subjects in TPC arm will have 1 of 3 standard of care (SOC) chemotherapeutic options
      including paclitaxel, docetaxel, and vinflunine. Subjects randomized to the sacituzumab
      govitecan arm will receive 10 mg/kg of sacituzumab govitecan intravenously on Day 1 and Day 8
      of 21-day cycles. Those randomized to the TPC arm will have the choice of receiving
      paclitaxel, docetaxel, and vinflunine administered intravenously at SOC doses of 175, 75 and
      320 mg/m2 respectively, on Day 1 of 21-day cycles.
    

Trial Arms

NameTypeDescriptionInterventions
sacituzumab govitecanExperimentalSubjects randomized to the treatment arm will receive 10 mg/kg of sacituzumab govitecan intravenously on Day 1 and Day 8 of 21-day cycles.
  • sacituzumab govitecan 10 mg/kg IV q21 day dosing
Treatment of Physician's ChoiceActive ComparatorThose randomized to the Treatment of Physician's Choice arm will have the choice of receiving paclitaxel, docetaxel, and vinflunine administered intravenously at SOC doses of 175, 75 and 320 mg/m2 respectively, on Day 1 of 21-day cycles.
  • Treatment of Physician's Choice of either paclitaxel 175 mg/m2, docetaxel 75 mg/m2 or vinflunine 320 mg/m2

Eligibility Criteria

        Inclusion Criteria:

          1. Female or male subjects, ≥18 years of age, able to understand and give written
             informed consent.

          2. Subjects with histologically documented metastatic or locally advanced unresectable UC
             defined as

             • Tumor (T) 4b, any node (N) or

             • Any T, N 2-3 Tumors of upper and lower urinary tract are permitted. Mixed histologic
             types are allowed if urothelial is the predominant histology.

          3. ECOG performance status (PS) score of 0 or 1.

          4. Subjects with progression or recurrence following receipt of platinum-containing
             regimen and anti PD-1/PD-L1 therapy for metastatic or locally advanced unresectable
             disease will be enrolled.

               1. Subjects with recurrence or progression ≤12 months following completion of
                  cisplatin-containing chemotherapy given in the neo-adjuvant/adjuvant setting may
                  utilize that line of therapy to be eligible for the study. The 12-month period is
                  counted from completion of surgical intervention or platinum therapy,
                  respectively. These subjects must receive anti PD-1/PD-L1 therapy in the
                  metastatic or locally advanced unresectable setting to be eligible.

               2. Subjects who received either carboplatin or anti PD-1/PD-L1 therapy in the neo-
                  adjuvant/adjuvant setting will not be able to count that line of therapy towards
                  eligibility for the study.

               3. Cisplatin ineligible subjects who meet one of the below criteria and who were
                  treated with carboplatin in the metastatic or locally advanced unresectable
                  settings may count that line of therapy towards eligibility. They must then have
                  received anti PD-1/PD-L1 therapy in metastatic or locally advanced unresectable
                  setting to be eligible for the study.

        Cisplatin ineligibility is defined as meeting one of the following criteria:

          1. Creatinine Clearance <60 mL/min

          2. Grade ≥2 Audiometric Hearing Loss

          3. Grade ≥2 Peripheral Neuropathy

          4. New York Heart Association (NYHA) Class III heart failure

          5. ECOG PS ≥2 d. Anti PD-1/PD-L1 therapy administered as part of maintenance therapy may
             be counted towards eligibility for the study Subjects who received only concurrent
             chemoradiation for bladder preservation without further systemic therapy are not
             eligible to enroll in the study. The substitution of carboplatin for cisplatin does
             not constitute a new regimen provided no new chemotherapeutic agents were added to the
             regimen and no progression was noted prior to the change in platinum.

        5. Subjects with previously treated brain metastases may participate in the study provided
        they have stable CNS disease for at least 4 weeks prior to the first dose of study drug and
        stabilization of all neurologic symptoms, have no evidence of new or enlarging brain
        metastases, and are not using steroids >20 mg of prednisone (or equivalent) daily for brain
        metastases for at least 7 days prior to first dose of the study drug.

        6. Adequate hematologic counts without transfusion or growth factor support within 1 week
        of study drug initiation (hemoglobin ≥9 g/dL, absolute neutrophil count [ANC]

        ≥1,500/mm3, and platelets ≥100,000/µL).

        7. Adequate hepatic function (bilirubin ≤1.5x institutional upper limit of normal [IULN],
        aspartate aminotransferase [AST] and alanine aminotransferase [ALT] ≤2.5 x IULN or

        ≤5 x IULN if known liver metastases and serum albumin >3 g/dL).

        Docetaxel will only be option in TPC arm for subjects with a total bilirubin ≤1 x IULN, and
        an AST and/or ALT ≤1.5x IULN if alkaline phosphatase is also >2.5 x IULN.

        8. Creatinine clearance ≥30 mL/min as assessed by the Cockcroft-Gault equation or other
        validated instruments (e.g. Modification of Diet in Renal Disease [MDRD] equation).

        9. Female subjects of childbearing potential must have a negative urine or serum pregnancy
        test within 72 hours prior to receiving the first dose of study drug. If the urine test is
        positive or cannot be confirmed as negative, a serum pregnancy test will be required.

        10. Female subjects of childbearing potential must be willing to use 2 methods of birth
        control or be surgically sterile or abstain from heterosexual activity for the course of
        the study through 6 months after the last dose of study drug. Subjects of childbearing
        potential are those who have not been surgically sterilized or have not been free from
        menses for >2 years.

        11. Male subjects must agree to use an adequate method of contraception starting with the
        first dose of study therapy through 3 months after the last dose of study therapy.

        Exclusion Criteria:

          1. Women who are pregnant or lactating.

          2. Have had a prior anti-cancer mAb/ ADC within 4 weeks prior to C1D1 or have had prior
             chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks
             prior to C1D1. Subjects participating in observational studies are eligible.

          3. Have received prior chemotherapy for UC with all available SOC therapies in the
             control arm (i.e., both prior paclitaxel and docetaxel in regions where vinflunine is
             not an approved therapy, or prior paclitaxel, docetaxel and vinflunine in regions
             where vinflunine is an approved therapy).

          4. Have not recovered (i.e., ≤Grade 1) from AEs due to previously administered
             chemotherapeutic agent.

               -  Note: Subjects with ≤Grade 2 neuropathy or any grade of alopecia are an exception
                  to this criterion and will qualify for the study.

               -  Note: If subjects received major surgery, they must have recovered adequately
                  from the toxicity and/or complications from the intervention prior to starting
                  study therapy.

          5. Have previously received topoisomerase 1 inhibitors.

          6. Have an active second malignancy.

             • Note: Subjects with a history of malignancy that have been completely treated and
             with no evidence of active cancer for 3 years prior to enrollment, or subjects with
             surgically cured tumors with low risk of recurrence are allowed to enroll in the study
             after discussion with the medical monitor.

          7. Have active cardiac disease, defined as:

               1. Myocardial infarction or unstable angina pectoris within 6 months of C1D1.

               2. History of serious ventricular arrhythmia (i.e., ventricular tachycardia or
                  ventricular fibrillation), high-grade atrioventricular block, or other cardiac
                  arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation
                  that is well controlled with antiarrhythmic medication); history of QT interval
                  prolongation.

               3. NYHA Class III or greater congestive heart failure or left ventricular ejection
                  fraction of <40%.

          8. Have active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease)
             or gastrointestinal (GI) perforation within 6 months of enrollment.

          9. Have an active serious infection requiring anti-infective therapy (Contact medical
             monitor for clarification).

         10. Have known history of Human Immunodeficiency Virus (HIV)-1/2 with undetectable viral
             load and on medications that may interfere with SN-38 metabolism.

         11. Have active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV). In subjects with a
             history of HBV or HCV, subjects with a detectable viral load will be excluded.

         12. Have other concurrent medical or psychiatric conditions that, in the investigator's
             opinion, may be likely to confound study interpretation or prevent completion of study
             procedures and follow-up examinations.

         13. Have inability to tolerate or are allergic to any potential TPC agent or sacituzumab
             govitecan or unable or unwilling to receive the doses specified in the protocol.

         14. Have inability to complete all specified study procedures for any reason.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Survival (OS)
Time Frame:Until study completion, up to 3.5 years
Safety Issue:
Description:OS is defined as time from the date of randomization to the date of death, regardless of cause

Secondary Outcome Measures

Measure:Progression-Free Survival (PFS)
Time Frame:Until study completion, up to 3.5 years
Safety Issue:
Description:PFS is defined as time from the date of randomization to the date of the first objectively documented disease progression, per investigator assessment and BICR using RECIST v1.1
Measure:Objective Response Rate (ORR)
Time Frame:Until study completion, up to 3.5 years
Safety Issue:
Description:ORR is defined as the proportion of subjects who achieved a complete response or partial response. ORR will be determined by investigator assessment and BICR using RECIST v1.1
Measure:Clinical Benefit Rate (CBR)
Time Frame:Until study completion, up to 3.5 years
Safety Issue:
Description:CBR is defined as the percentage of patients with advanced or metastatic cancer who have achieved complete response, partial response and stable disease for greater than or equal to 6 months to therapeutic intervention in a clinical study. CBR will be determined by investigator assessment and BICR using RECIST v1.1
Measure:Duration of Objective Tumor Response (DOR)
Time Frame:Until study completion, up to 3.5 years
Safety Issue:
Description:DOR is defined as the time from the date when the criteria is first met for a complete response or partial response to the first date that disease progression is documented as determined by investigator assessment and BICR using RECIST v1.1
Measure:Rate of adverse events, serious adverse events and laboratory changes
Time Frame:Until study completion, up to 3.5 years
Safety Issue:
Description:Assessment of sacituzumab govitecan (IMMU-132) safety and tolerability compared to treatment of physician's choice
Measure:European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QC-30)
Time Frame:Until study completion, up to 3.5 years
Safety Issue:
Description:Quality of life Questionnaire for cancer patients. Scoring of the QLQ-C30 is performed according to QLQ-C30 Scoring manual. All of the scales and single-item measures range in score from 0 to 100. Higher score for the functioning scales and global health status denote a better level of functioning (i.e. a better state of the patient), while higher scores on the symptom and single-item scales indicate a higher level of symptoms (i.e. a worse state of the patient).
Measure:European Quality of Life 5-Dimensions 5 Levels instrument (EuroQOL EQ-5D-5L)
Time Frame:Until study completion, up to 3.5 years
Safety Issue:
Description:The EQ-5D-5L is a self-assessed, health related, quality of life questionnaire. The EQ-5D-3L descriptive system comprises the following five dimensions, each describing a different aspect of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has three response levels of severity: no problems, some problems, extreme problems. The respondent is asked to indicate his/her health state by checking the box next to the most appropriate response level of each of the five dimensions. EQ-5D-5L health states can be summarized using the 5-digit code or represented by a single summary number (index value), which reflects how good or bad a health state is according to the preferences of the general population of a country/region.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Gilead Sciences

Last Updated

April 2, 2021