Clinical trial NCT01631552: Study of Sacituzumab Govitecan-hziy (IMMU-132) in Adults With Epithelial Cancer
Official title: A Phase I/II Study of IMMU-132 (hRS7-SN38 Antibody Drug Conjugate) in Patients With Epithelial Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Gastric Adenocarcinoma
Esophageal Cancer
Hepatocellular Carcinoma
Non-small Cell Lung Cancer
Small Cell Lung Cancer
Ovarian Epithelial Cancer
Carcinoma Breast Stage IV
Hormone-refractory Prostate Cancer
Head and Neck Cancers- Squamous Cell
Renal Cell Cancer
Urinary Bladder Neoplasms
Cervical Cancer
Endometrial Cancer
Glioblastoma Multiforme
Triple Negative Breast Cancer
Pancreatic Cancer
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2012-06-29
Enrollment: 515
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The primary objective in Phase I is to evaluate the safety and tolerability of sacituzumab govitecan-hziy (SG) as a single agent administered in 21-day treatment cycles in previously treated participants with advanced epithelial cancer. In Phase II, the primary objective is to evaluate the safety and efficacy of sacituzumab govitecan-hziy administered in 21-day treatment cycles at a dose selected in Phase I.

Tumor types in the study will include: cervical, colorectal, endometrial, ovarian, esophageal, gastric adenocarcinoma, glioblastoma multiforme, head and neck cancers- squamous cell, hepatocellular, prostate, non-small-cell lung cancer, pancreatic, renal cell, small-cell lung cancer, non-triple negative breast cancer (non-TNBC), triple-negative breast cancer (TNBC) and metastatic urothelial cancer (mUC).

Detailed description: The outcome measures are planned to be assessed up to the data cutoff date. Following the data cutoff date, the participants will either stay on the study and will be followed for safety data collection or rolled into another Gilead-sponsored study. Therefore, only safety data will be collected after the data cutoff date.

Eligibility criteria: Inclusion Criteria:

* Individuals able to understand and give written informed consent.
* Histologically or cytologically confirmed epithelial cancer of one of the following types:

  * Gastric adenocarcinoma (GC)
  * Esophageal cancer (EC)
  * Hepatocellular carcinoma (HCC)
  * Non-small-cell lung cancer (NSCLC)
  * Small-cell lung cancer (SCLC)
  * Epithelial ovarian cancer (EOC)
  * Cervical Cancer
  * Endometrial Cancer
  * Triple-negative breast cancer (TNBC)
  * Non-triple-negative breast cancer
  * Papillary thyroid cancer (excludes follicular, medullary, Hurthle cell, and anaplastic thyroid cancer)
  * Glioblastoma multiforme (GBM)
  * Hormone-refractory prostate cancer (HRPC)
  * Head and neck cancers- squamous cell (SCCHN)
  * Renal cell cancer (clear cell) (RCC)
  * Urothelial cancer
  * Stage IV (metastatic) disease (except for individuals with GBM).
* Refractory to or relapsed after at least one prior standard therapeutic regimen
* Adequate performance status (ECOG 0 or 1)
* Expected survival ≥ 6 months.
* Measurable disease by CT or MRI.
* At least 2 weeks beyond treatment (chemotherapy, investigational drugs including small molecular inhibitors, immunotherapy and/or radiation therapy) or major surgery and recovered from all acute toxicities to Grade 1 or less (except alopecia).
* 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, absolute neutrophil count (ANC) \> 1,500 per mm\^3, platelets \> 100,000 per mm\^3).
* Adequate renal and hepatic function (creatinine ≤ 2.0 x institutional upper limit of normal (IULN), bilirubin ≤ 1.5 IULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x IULN or 5 x IULN if know liver metastases).
* Otherwise, all toxicity at study entry ≤ Grade 1.

Exclusion Criteria:

* Women who are pregnant or lactating.
* Women of childbearing potential and fertile men unwilling to use effective contraception during study until conclusion of 12-week post-treatment evaluation period.
* Individuals with Gilbert's disease.
* Individuals with brain metastases can be enrolled only if treated, non-progressive brain metastases and off high-dose steroids (\> 20 mg prednisone or equivalent) for at least 4 weeks.
* Presence of bulky disease (defined as any single mass \> 7 cm in its greatest dimension). Individuals with a mass over 7 cm, but otherwise eligible, may be considered for enrollment after discussion and approval with the medical monitor.
* Individuals with active ≥ grade 2 anorexia, nausea or vomiting, and/or signs of intestinal obstruction.
* Individuals with non-melanoma skin cancer or carcinoma in situ of the cervix are eligible, while individuals with other prior malignancies must have had at least a 3-year disease-free interval.
* Individuals known to be HIV positive, hepatitis B positive, or hepatitis C positive.
* Known history of unstable angina, MI, or CHF present within 6 months or clinically significant cardiac arrhythmia (other than stable atrial fibrillation) requiring anti-arrhythmia therapy.
* Known history of clinically significant active COPD, or other moderate-to-severe chronic respiratory illness present within 6 months.
* Prior history of clinically significant bleeding, intestinal obstruction, or GI perforation within 6 months of initiation of study treatment.
* Infection requiring intravenous antibiotic use within 1 week.
* History of an anaphylactic reaction to irinotecan or ≥ Grade 3 GI toxicity to prior 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.

Primary outcomes:
measure: Percentage of Participants Experiencing Any Treatment Emergent Adverse Events and Serious Treatment Emergent Adverse Events
timeFrame: First dose date up to last dose for data cutoff date of 01 March 2019 (maximum duration: 55.2 months) plus 30 days
measure: Percentage of Participants Who Permanently Discontinued Sacituzumab Govitecan-hziy (SG) Due to Any Adverse Events, Excluding Adverse Events Leading to Death
timeFrame: First dose date up to last dose for data cutoff date of 01 March 2019 (maximum duration: 55.2 months)
measure: Percentage of Participants Who Required Dose Interruption Due to Any Adverse Events
timeFrame: First dose date up to last dose for data cutoff date of 01 March 2019 (maximum duration: 55.2 months)
measure: Objective Response Rate (ORR) by Independent Central Review (ICR)
timeFrame: Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)
measure: Objective Response Rate by Local Assessment
timeFrame: Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)
Secondary outcomes:
measure: Duration of Response by ICR
timeFrame: Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)
measure: Duration of Response by Local Assessment
timeFrame: Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)
measure: Time to Response by ICR
timeFrame: Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)
measure: Time to Response by Local Assessments
timeFrame: Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)
measure: Clinical Benefit Rate (CBR) by Local Assessment
timeFrame: Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)
measure: Progression Free Survival (PFS) by Local Assessment
timeFrame: Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)
measure: Overall Survival by Local Assessment
timeFrame: Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)
measure: Pharmacokinetic (PK) Parameter: T1/2 of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38
timeFrame: Cycle 1: Preinfusion, 30 minutes and 3-4 hours post infusion, then 1 day, 2 days, 3 days, and 7 days later (1 Cycle = 21 days). Infusion duration: 3 hours (± 30 minutes) for 1st infusion; 1-2 hours (± 30 minutes) for subsequent infusions
measure: PK Parameter: AUC0-24 of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38
timeFrame: Cycle 1: Preinfusion, 30 minutes and 3-4 hours post infusion, then 1 day, 2 days, 3 days, and 7 days later (1 Cycle = 21 days). Infusion duration: 3 hours (± 30 minutes) for 1st infusion; 1-2 hour (± 30 minutes) for subsequent infusions
measure: PK Parameter: AUC0-168 of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38
timeFrame: Cycle 1: Preinfusion, 30 minutes and 3-4 hours post infusion, then 1 day, 2 days, 3 days, and 7 days later (1 Cycle = 21 days). Infusion duration: 3 hours (± 30 minutes) for 1st infusion; 1-2 hour (± 30 minutes) for subsequent infusions
measure: PK Parameter: AUC0-inf of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38
timeFrame: Cycle 1: Preinfusion, 30 minutes and 3-4 hours post infusion, then 1 day, 2 days, 3 days, and 7 days later (1 Cycle = 21 days). Infusion duration: 3 hours (± 30 minutes) for 1st infusion; 1-2 hour (± 30 minutes) for subsequent infusions
measure: PK Parameter: Cmax of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38
timeFrame: Cycle 1: Preinfusion, 30 minutes and 3-4 hours post infusion, then 1 day, 2 days, 3 days, and 7 days later (1 Cycle = 21 days). Infusion duration: 3 hours (± 30 minutes) for 1st infusion; 1-2 hour (± 30 minutes) for subsequent infusions
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Newark
country: United States
facility: Helen F. Graham Cancer Center
state: Delaware
city: Orlando
country: United States
facility: MD Anderson Cancer Center Orlando (UF Health Cancer Center)
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Goshen
country: United States
facility: IU Health Goshen Cancer Center
state: Indiana
city: Boston
country: United States
facility: Massachusettes General Hospital
state: Massachusetts
city: New York
country: United States
facility: Weill Cornell/New York Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Columbia University Herbert Irving Cancer Center
state: New York
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology Sammons Cancer Center
state: Texas
city: Seattle
country: United States
facility: Virginia Mason Cancer Center
state: Washington
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
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