ASCENT-Study of Sacituzumab Govitecan in Refractory/Relapsed Triple-Negative Breast Cancer (ASCENT)
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|ClinicalTrials.gov Identifier: NCT02574455|
Recruitment Status : Recruiting
First Posted : October 12, 2015
Last Update Posted : August 14, 2019
|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer||Drug: Sacituzumab govitecan Drug: Eribulin Drug: Capecitabine Drug: Gemcitabine Drug: Vinorelbine||Phase 3|
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 :||Interventional (Clinical Trial)|
|Estimated Enrollment :||488 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase III Study of Sacituzumab Govitecan (IMMU-132) in Refractory/Relapsed Triple-Negative Breast Cancer|
|Actual Study Start Date :||October 12, 2017|
|Estimated Primary Completion Date :||December 2019|
|Estimated Study Completion Date :||June 2020|
Sacituzumab govitecan (10 mg/kg on Days 1 and 8 of 21-day cycles)
Drug: Sacituzumab govitecan
Sacituzumab govitecan (10 mg/kg on Days 1 and 8 of 21-day cycles)
Other Name: IMMU-132
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)
Eribulin (1.4 mg/m2 IV on Days 1 and 8 of a 21-day cycle) See section 6.5.1
Other Name: Halaven
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
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
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
- Progression-Free Survival (PFS): [ Time Frame: 3 YEARS ]PFS
- 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.
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): NCT02574455
|Contact: Medical Informationemail@example.com|
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|Study Chair:||William Wegener, MD,PhD||Immunomedics, Inc.|