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ASCENT-Study of Sacituzumab Govitecan in Refractory/Relapsed Triple-Negative Breast Cancer (ASCENT)

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ClinicalTrials.gov Identifier: NCT02574455
Recruitment Status : Active, not recruiting
First Posted : October 12, 2015
Last Update Posted : September 23, 2019
Sponsor:
Information provided by (Responsible Party):
Immunomedics, Inc.

Tracking Information
First Submitted Date  ICMJE October 8, 2015
First Posted Date  ICMJE October 12, 2015
Last Update Posted Date September 23, 2019
Actual Study Start Date  ICMJE October 12, 2017
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 9, 2015)
Progression-Free Survival (PFS): [ Time Frame: 3 YEARS ]
PFS
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02574455 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 9, 2015)
  • Overall Survival (OS): [ Time Frame: 3 YEARS ]
    OS will compared between the two treatment groups. PFS will be measured by an independent centralized and blinded group of radiology experts who will be assessing tumor response using RECIST 1.1 criteria. FDA definitions and guidance as described in Guidance for Industry:
  • Objective Response Rate [ Time Frame: 3 years ]
    ORR will compared between the two treatment groups.
  • Duration of Response [ Time Frame: 3 years ]
    Duration of response will compared between the two treatment groups.
  • Time to Onset of response [ Time Frame: 3 years ]
    Time to onset of response will compared between the two treatment groups.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE ASCENT-Study of Sacituzumab Govitecan in Refractory/Relapsed Triple-Negative Breast Cancer
Official Title  ICMJE Phase III Study of Sacituzumab Govitecan (IMMU-132) in Refractory/Relapsed Triple-Negative Breast Cancer
Brief Summary This is an international, multi-center, open-label, randomized, Phase III study in patients with metastatic TNBC refractory or relapsing after at least 2 prior chemotherapies (including a taxane) for their metastatic disease. Patients meeting eligibility will be randomized 1:1 to receive either sacituzumab govitecan or treatment of physician choice (TPC) Patients will be treated until progression, unacceptable toxicity, study withdrawal, or death, whichever comes first. Tumor progression leading to treatment withdrawal will be assessed by the investigator. Starting with the initial dose of sacituzumab govitecan or TPC, Imaging assessments will be obtained at least every 8 weeks until the occurrence of progression of disease requiring discontinuation of further treatment. All patients, will be followed every 4 weeks during the first year and every 8 weeks thereafter for survival follow-up.
Detailed Description

This is an international, multi-center, open-label, randomized, Phase III study in patients with metastatic TNBC refractory or relapsing after at least 2 prior chemotherapies (including a taxane) for their metastatic disease.

The primary objective of this study is to compare the efficacy of sacituzumab govitecan to the treatment of physician's choice (TPC) as measured by progression-free survival (PFS) in patients with metastatic TNBC previously treated with at least two systemic chemotherapy regimens.

The secondary objectives of the study are to compare between the two treatment groups for:

  • Overall Survival (OS)
  • Independently-determined Objective Response Rate (ORR), duration of response and time to onset of response per RECIST 1.1 criteria
  • Quality of life
  • Safety (adverse events, safety laboratories, incidence of dose delays and dose reductions, treatment discontinuations due to adverse events) Exploratory objectives include exposure-response analysis for the efficacy (PFS and OS) and safety (incidence of Grade 3-5 adverse events, related to UGT1A1 endpoints).

Four-Hundred and eighty-eight patients are anticipated to be enrolled. Approximately 150 institutions will participate in this study, including sites in North America and Europe.

Clinical sites will use standard ASCO/CAP criteria for the pathological diagnosis of TNBC, defined as negative for estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). Receptor results will be based on local assessment. TNBC status will be reviewed centrally but these results are not required prior to determining eligibility.

BRCA 1&2 mutational status will be collected, if known. Baseline serum biomarkers (CA15-3, CA27-29, and CEA) will be measured. A single whole-blood sample will be also collected from all patients for determination of UGT1A1 genotype for retrospective assessment predicting of toxicity.

The Sponsor will request slides from prior (archived) biopsy or surgical specimens, particularly for immunohistology documentation of tumor Trop-2 expression and other appropriate tumor markers, including topoisomerase 1.

Patients meeting eligibility will be randomized 1:1 to receive either sacituzumab govitecan or treatment of physician choice (TPC), which needs to be selected prior to randomization from one of the 4 allowed regimens. Randomization will be stratified by number of prior chemotherapies for advanced disease (2-3 vs > 3) and geographical location (North America vs Europe).

Patients will be treated until progression, unacceptable toxicity, study withdrawal, or death, whichever comes first. Tumor progression leading to treatment withdrawal will be assessed by the investigator.

No crossover to sacituzumab govitecan treatment will be allowed after discontinuing treatment in the TPC arm, but otherwise there is no restriction on subsequent therapies that a patient may receive after discontinuing the study.

All patients, including those prematurely terminating study participation, will be followed every 4 weeks for survival follow-up.

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 Breast Cancer
Intervention  ICMJE
  • Drug: Sacituzumab govitecan
    Sacituzumab govitecan (10 mg/kg on Days 1 and 8 of 21-day cycles)
    Other Name: IMMU-132
  • Drug: Eribulin
    Eribulin (1.4 mg/m2 IV on Days 1 and 8 of a 21-day cycle) See section 6.5.1
    Other Name: Halaven
  • Drug: Capecitabine
    Capecitabine (1000-1250 mg/m2 orally twice daily on Days 1-14 of a 21-day cycle) See section 6.5.2
    Other Name: Xeloda
  • Drug: Gemcitabine
    Gemcitabine (800-1200 mg/m2 IV on Days 1, 8 and 15 of a 28-day cycle). See section 6.5.3
    Other Name: Gemzar
  • Drug: Vinorelbine
    Vinorelbine (25 mg/m2 IV on Day 1 weekly). See section 6.5.4 (Note: eligible patients with Grade 2 neuropathy should not be prescribed vinorelbine as TPC).
    Other Name: Navelbine
Study Arms  ICMJE
  • Experimental: IMMU-132
    Sacituzumab govitecan (10 mg/kg on Days 1 and 8 of 21-day cycles)
    Intervention: Drug: Sacituzumab govitecan
  • Active Comparator: Control Arm

    Treatment of Physician's Choice determined before randomization from only one of the following treatments (see Appendix 2 for more details on administration and dosing management):

    Eribulin (1.4 mg/m2 IV on Days 1 and 8 of a 21-day cycle). See section 6.5.1 Capecitabine (1000-1250 mg/m2 orally twice daily on Days1-14 of a 21-day cycle). See section 6.5.2 Gemcitabine (800-1200 mg/m2 IV on Days 1, 8 and 15 of a 28-day cycle). See section 6.5.3 Vinorelbine (25 mg/m2 weekly IV on Day 1 weekly) See section 6.5.4 (Note: eligible patients with Grade 2 neuropathy should not be prescribed vinorelbine as TPC)

    Interventions:
    • Drug: Eribulin
    • Drug: Capecitabine
    • Drug: Gemcitabine
    • Drug: Vinorelbine
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 Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: September 19, 2019)
529
Original Estimated Enrollment  ICMJE
 (submitted: October 9, 2015)
328
Estimated Study Completion Date  ICMJE June 2020
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Female or male patients, >18 years of age, able to understand and give written informed consent.
  • Histologically or cytologically confirmed TNBC based on the most recent analyzed biopsy or other pathology specimen. TNBC determination as per local institution as per standard guidelines.
  • Refractory to or relapsed after at least two prior standard therapeutic regimens for advanced/metastatic TNBC.
  • Prior exposure to a taxane (paclitaxel or docetaxel)-based regimen in localized or advanced/metastatic setting.
  • Eligible for one of the chemotherapy options listed as TPC (Eribulin, capecitabine, gemcitabine, or vinorelbine) as per investigator assessment.
  • ECOG performance score of 0 or 1 .
  • Measurable disease by CT or MRI as per RECIST 1.1. Bone-only disease is not permitted.
  • At least 2 weeks beyond prior treatment (chemotherapy, investigational drugs including small molecular inhibitors, endocrine therapy, immunotherapy and/or radiation therapy) or major surgery, and recovered from all acute toxicities to Grade 1 or less (except alopecia and peripheral neuropathy).
  • At least 2 weeks beyond high dose systemic corticosteroids (however, low dose corticosteroids < 20 mg prednisone or equivalent daily are permitted).
  • Adequate hematology without ongoing transfusional support (hemoglobin > 9 g/dL, ANC > 1,500 per mm3, platelets > 100,000 per mm3).
  • Adequate renal and hepatic function (creatinine ≤ 2.0 x IULN, bilirubin ≤ 1.5 IULN, AST and ALT ≤ 3.0 x IULN or 5 x IULN if known liver metastases).
  • Otherwise, all toxicity at study entry < Grade 1 by NCI CTCAE v4.00 (Patients with ≤ Grade 2 neuropathy are eligible).
  • Patients with treated, non-progressive brain metastases, off high-dose steroids (>20 mg prednisone or equivalent) for at least 4 weeks can be enrolled in the trial.

Exclusion Criteria:

  • Women who are pregnant or lactating.
  • Women of childbearing potential or fertile men unwilling to use effective contraception during study until conclusion of 4-week post-treatment evaluation period.
  • Patients with Gilbert's disease.
  • Patients with active ≥ grade 2 anorexia, nausea or vomiting, and/or signs of intestinal obstruction.
  • Patients with non-melanoma skin cancer or carcinoma in situ of the cervix are eligible, while patients with other prior malignancies must have had at least a 3-year disease-free interval.
  • Patients known to be HIV positive, hepatitis B positive, or hepatitis C positive.
  • Infection requiring intravenous antibiotic use within one week of enrollment.
  • Patients with a history of an anaphylactic reaction to irinotecan.
  • 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.
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 information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States,   Belgium,   Canada,   France,   Germany,   Spain,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02574455
Other Study ID Numbers  ICMJE IMMU-132-05
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: Undecided
Responsible Party Immunomedics, Inc.
Study Sponsor  ICMJE Immunomedics, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: William Wegener, MD,PhD Immunomedics, Inc.
PRS Account Immunomedics, Inc.
Verification Date September 2019

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