Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of Sacituzumab Govitecan (IMMU-132) in Metastatic or Locally Advanced Unresectable Urothelial Cancer (TROPiCS-04)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04527991
Recruitment Status : Not yet recruiting
First Posted : August 27, 2020
Last Update Posted : August 27, 2020
Sponsor:
Information provided by (Responsible Party):
Immunomedics, Inc.

Brief Summary:

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 482 subjects from 90 global sites will be enrolled


Condition or disease Intervention/treatment Phase
Urothelial Carcinoma Bladder Cancer Metastatic Urothelial Carcinoma Locally Advanced Urothelial Cancer Transitional Cell Carcinoma Drug: sacituzumab govitecan 10 mg/kg IV q21 day dosing Drug: Treatment of Physician's Choice of either paclitaxel 175 mg/m2, docetaxel 75 mg/m2 or vinflunine 320 mg/m2 Phase 3

Detailed Description:

This is a Phase III, global, multicenter, open-label randomized controlled trial in which approximately 482 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 482 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Estimated Study Start Date : December 2020
Estimated Primary Completion Date : April 2023
Estimated Study Completion Date : June 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: sacituzumab govitecan
Subjects randomized to the treatment arm will receive 10 mg/kg of sacituzumab govitecan intravenously on Day 1 and Day 8 of 21-day cycles.
Drug: sacituzumab govitecan 10 mg/kg IV q21 day dosing
Doses on days 1 and 8 of 21-day cycle
Other Name: IMMU-132

Active Comparator: Treatment of Physician's Choice
Those 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.
Drug: Treatment of Physician's Choice of either paclitaxel 175 mg/m2, docetaxel 75 mg/m2 or vinflunine 320 mg/m2
Dosing on Day 1 of 21-day cycle




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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).

  7. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 score of 0 or 1.
  4. Subjects with progression or recurrence following receipt of platinum-containing regimen (cisplatin or carboplatin) 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 platinum-containing chemotherapy and/or anti PD-1/PD-L1 therapy given in 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 platinum therapy or surgical intervention.
    2. 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 ≤ 1.5 x institution 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 ≤ 1.5 x 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. New York Heart Association (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 uncontrolled 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.

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): NCT04527991


Contacts
Layout table for location contacts
Contact: Dianne Nowicke, MS 908-255-7203 dnowicke@immunomedics.com
Contact: John Benedetto 862-260-3677 jbenedetto@immunomedics.com

Sponsors and Collaborators
Immunomedics, Inc.
Investigators
Layout table for investigator information
Study Director: Cabilia C. Pichardo, MD Immunomedics, Inc.
Layout table for additonal information
Responsible Party: Immunomedics, Inc.
ClinicalTrials.gov Identifier: NCT04527991    
Other Study ID Numbers: IMMU-132-13
First Posted: August 27, 2020    Key Record Dates
Last Update Posted: August 27, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Paclitaxel
Docetaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action