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Study of Sacituzumab Govitecan-hziy (IMMU-132) Versus Treatment of Physician's Choice in Participants With Metastatic or Locally Advanced Unresectable Urothelial Cancer (TROPiCS-04)

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ClinicalTrials.gov Identifier: NCT04527991
Recruitment Status : Recruiting
First Posted : August 27, 2020
Last Update Posted : October 27, 2021
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Tracking Information
First Submitted Date  ICMJE August 19, 2020
First Posted Date  ICMJE August 27, 2020
Last Update Posted Date October 27, 2021
Actual Study Start Date  ICMJE January 13, 2021
Estimated Primary Completion Date June 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 27, 2021)
Overall Survival (OS) [ Time Frame: Up to 3.5 years ]
OS is defined as time from the date of randomization to the date of death, regardless of cause.
Original Primary Outcome Measures  ICMJE
 (submitted: August 22, 2020)
Overall Survival (OS) [ Time Frame: Until study completion, up to 3.5 years ]
OS is defined as time from the date of randomization to the date of death, regardless of cause
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 27, 2021)
  • Progression-Free Survival (PFS) by Investigator Assessment [ Time Frame: Up to 3.5 years ]
    PFS is defined as the time from the date of randomization to the date of the first objectively documented disease progression, per response evaluation criteria in solid tumors version 1.1 (RECIST v1.1) criteria, as determined by investigator assessment, or death regardless of cause, whichever occurs first.
  • Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR) [ Time Frame: Up to 3.5 years ]
    PFS is defined as the time from the date of randomization to the date of the first objectively documented disease progression, per RECIST v1.1 criteria as determined by BICR, or death regardless of cause, whichever occurs first.
  • Objective Response Rate (ORR) by Investigator Assessment [ Time Frame: Up to 3.5 years ]
    ORR is defined as the proportion of participants who achieved a complete response or partial response as best overall response (BOR). BOR is determined per RECIST 1.1 as determined by investigator assessment.
  • Objective Response Rate (ORR) by BICR [ Time Frame: Up to 3.5 years ]
    ORR is defined as the proportion of participants who achieved a complete response or partial response as best overall response (BOR). BOR is determined per RECIST 1.1 as determined by BICR.
  • Clinical Benefit Rate (CBR) by Investigator Assessment [ Time Frame: Up to 3.5 years ]
    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 per RECIST v1.1 by investigator assessment.
  • Clinical Benefit Rate (CBR) by BICR [ Time Frame: Up to 3.5 years ]
    CBR is defined as the percentage of participants 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 per RECIST v1.1 by BICR.
  • Duration of Objective Tumor Response (DOR) by Investigator Assessment [ Time Frame: Up to 3.5 years ]
    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 per RECIST 1.1 as determined by investigator assessment, or date of death, whichever occurs first.
  • Duration of Objective Tumor Response (DOR) by BICR [ Time Frame: Up to 3.5 years ]
    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 per RECIST 1.1 as determined by BICR, or date of death, whichever occurs first.
  • Percentage of Participants Experiencing any Treatment Emergent Adverse Events [ Time Frame: Up to 3.5 years ]
  • Percentage of Participants Experiencing any Serious Treatment Emergent Adverse Events [ Time Frame: Up to 3.5 years ]
  • Percentage of Participants Experiencing any Clinically Significant Laboratory Abnormalities [ Time Frame: Up to 3.5 years ]
  • European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) Score [ Time Frame: Up to 3.5 years ]
    The EORTC QLQ-C30 is a questionnaire to assess quality of life of cancer patients, it is composed of 30 questions (items) resulting in 5 functional scales, 1 global health status scale, 3 symptom scales, and 6 single items. 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 participant), while higher scores on the symptom and single-item scales indicate a higher level of symptoms (i.e. a worse state of the participant).
  • European Quality of Life 5-Dimensions 5 Levels Instrument (EuroQOL EQ-5D-5L) Score [ Time Frame: Up to 3.5 years ]
    The EQ-5D-5L is a standard measure of health-related quality of life. The tool consists of the EQ-5D-5L descriptive part and the EQ visual analogue scale (VAS). The descriptive part comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Each of these 5 dimensions has 5 levels (no problem, slight problems, moderate problems, severe problems, and extreme problems). Results for each of the 5 dimensions are combined into a 5-digit number to describe the participant's health state. The EQ-VAS records the participant's health on a 0-100 mm VAS scale, with 0 indicating "the worst health you can imagine" and 100 indicating "the best health you can imagine." Higher scores of EQ VAS indicate better health.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 22, 2020)
  • Progression-Free Survival (PFS) [ Time Frame: Until study completion, up to 3.5 years ]
    PFS is defined as time from the date of randomization to the date of the first objectively documented disease progression, per RECIST v1.1
  • Objective Response Rate (ORR) [ Time Frame: Until study completion, up to 3.5 years ]
    ORR is defined as the proportion of subjects who achieved a complete response or partial response
  • Clinical Benefit Rate (CBR) [ Time Frame: Until study completion, up to 3.5 years ]
    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 RECIST v1.1
  • Duration of Objective Tumor Response (DOR) [ Time Frame: Until study completion, up to 3.5 years ]
    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 RECIST v1.1
  • Rate of adverse events, serious adverse events and laboratory changes [ Time Frame: Until study completion, up to 3.5 years ]
    Assessment of sacituzumab govitecan (IMMU-132) safety and tolerability compared to treatment of physician's choice
  • 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 ]
    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).
  • European Quality of Life 5-Dimensions 5 Levels instrument (EuroQOL EQ-5D-5L) [ Time Frame: Until study completion, up to 3.5 years ]
    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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Sacituzumab Govitecan-hziy (IMMU-132) Versus Treatment of Physician's Choice in Participants With Metastatic or Locally Advanced Unresectable Urothelial Cancer
Official Title  ICMJE 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)
Brief Summary The primary objective of this study is to assess overall survival (OS) with sacituzumab govitecan-hziy in comparison with treatment of physician's choice (TPC) in participants with metastatic or locally advanced unresectable urothelial cancer (UC).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Locally Advanced or Metastatic Unresectable Urothelial Cancer
Intervention  ICMJE
  • Biological: Sacituzumab Govitecan-hziy
    Administered intravenously
    Other Names:
    • IMMU-132
    • Trodelvy™
  • Drug: Paclitaxel
    Administered intravenously
    Other Name: Taxol®
  • Drug: Docetaxel
    Administered intravenously
    Other Name: Taxotere®
  • Drug: Vinflunine
    Administered intravenously
    Other Name: Javlor ®
Study Arms  ICMJE
  • Experimental: Sacituzumab Govitecan-hziy
    Participants will receive 10 mg/kg of sacituzumab govitecan-hziy intravenously on Day 1 and Day 8 of 21-day cycles.
    Intervention: Biological: Sacituzumab Govitecan-hziy
  • Active Comparator: Treatment of Physician's Choice
    Participants will have the choice of receiving paclitaxel, docetaxel, or vinflunine at standard of care (SOC) doses of 175, 75, and 320 mg/m^2 respectively, every 3 weeks on Day 1 of 21-day cycles.
    Interventions:
    • Drug: Paclitaxel
    • Drug: Docetaxel
    • Drug: Vinflunine
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: January 12, 2021)
600
Original Estimated Enrollment  ICMJE
 (submitted: August 22, 2020)
482
Estimated Study Completion Date  ICMJE January 2024
Estimated Primary Completion Date June 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Individuals 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.
  2. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1.
  3. Individuals with progression or recurrence following receipt of platinum-containing regimen and anti programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) therapy for metastatic or locally advanced unresectable disease will be enrolled.

    • a. Individuals 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 individuals must receive anti PD-1/PD-L1 therapy in the metastatic or locally advanced unresectable setting to be eligible.
    • b. Individuals 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.
    • c. Cisplatin ineligible individuals 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
    • e. Individuals 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.
  4. Individuals 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.
  5. 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/mm^3, and platelets ≥100,000/µL).
  6. 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 Individuals 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.

  7. 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).
  8. Females 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.
  9. Females 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. Individuals of childbearing potential are those who have not been surgically sterilized or have not been free from menses for >2 years.
  10. Male individuals 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. Females who are pregnant or lactating.
  2. Have had a prior anti-cancer monoclonal antibody (mAb)/ antibody-drug conjugate (ADC) within 4 weeks prior to Cycle 1 Day 1 (C1D1) or have had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to C1D1. Individuals 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: Individuals with ≤ Grade 2 neuropathy or any grade of alopecia are an exception to this criterion and will qualify for the study.
    • Note: If Individuals 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: Individuals with a history of malignancy that have been completely treated and with no evidence of active cancer for 3 years prior to enrollment, or individuals 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:

    • Myocardial infarction or unstable angina pectoris within 6 months of C1D1.
    • 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.
    • 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 individuals with a history of HBV or HCV, individuals 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-hziy or unable or unwilling to receive the doses specified in the protocol.
  14. Have inability to complete all specified study procedures for any reason.
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: Gilead Clinical Study Information Center 1-833-445-3230(GILEAD-0) GileadClinicalTrials@gilead.com
Listed Location Countries  ICMJE Australia,   Belgium,   Canada,   China,   France,   Germany,   Puerto Rico,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04527991
Other Study ID Numbers  ICMJE IMMU-132-13
2020-002964-29 ( EudraCT Number )
Has Data Monitoring Committee Yes
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 Gilead Sciences
Study Sponsor  ICMJE Gilead Sciences
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Gilead Study Director Gilead Sciences
PRS Account Gilead Sciences
Verification Date October 2021

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