Study of Labetuzumab Govitecan in Participants With Metastatic Colorectal Cancer

Phase 1

Terminated

• Conditions: Colon Cancer; Rectal Cancer; Metastatic Colorectal Cancer
• Interventions: Drug: Labetuzumab Govitecan (LG)

• Registration Number: NCT01605318
• Lead Sponsor: Gilead Sciences

Brief Summary

The goal of this clinical study is to determine the dosing and safety of labetuzumab govitecan (formerly known as IMMU-130; hMN-14-SN38, antibody-drug conjugate) in participants with colorectal cancer.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-05-22
• Study First Submitted QC: 2012-05-23
• Study First Posted: 2012-05-24
• Study Start: 2013-02-12
• Primary Completion: 2017-01-03
• Study Completion: 2017-01-03
• Status Verified: 2024-01
• Disposition First Submitted: 2024-01-22
• Last Update Submitted: 2024-01-22
• Disposition First Posted: 2024-01-24
• Last Update Posted: 2024-01-24

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 92

Inclusion Criteria

• Histologically or cytologically confirmed colorectal adenocarcinoma.
• Stage IV (metastatic) disease.
• Previously treated with at least one prior irinotecan-containing regimen for colorectal cancer.
• Adequate performance status (Eastern Cooperative Oncology Group (ECOG) 0 or 1).
• Expected survival > 6 months.
• Carcinoembryonic antigen (CEA) plasma levels > 5 ng/mL.
• Measurable disease by computed tomography (CT) or Magnetic resonance imaging (MRI).
• At least 4 weeks beyond treatment (chemotherapy, immunotherapy and/or radiation therapy) or major surgery and recovered from all acute toxicities.
• At least 2 weeks beyond corticosteroids.
• 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 ≤ 1.5 x IULN, bilirubin ≤ institutional upper limit of normal (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 by National cancer institute common terminology criteria for adverse events (NCI CTC) v4.0.

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 or known central nervous system (CNS) metastatic disease.
• Individuals with CEA plasma levels > 1000 ng/mL must be approved in advance by the Sponsor.
• Presence of bulky disease (defined as any single mass > 10 cm in its greatest dimension).
• 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 human immunodeficiency virus (HIV) positive, hepatitis B positive, or hepatitis C positive.
• Known history of unstable angina, myocardial infarction, or congestive heart failure present within 6 months or clinically significant cardiac arrhythmia (other than stable atrial fibrillation) requiring anti-arrhythmia therapy.
• Known history of clinically significant active chronic obstructive pulmonary disease (COPD), or other moderate-to-severe chronic respiratory illness present within 6 months.
• Infection requiring intravenous antibiotic use within 1 week.
• 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Phase 2: Dose-expansion Phase: LG Once or Twice Weekly Dosing	Labetuzumab Govitecan (LG)	Participants will receive selected doses of LG once or twice weekly until unacceptable toxicity, progressive disease or death whichever occurs first, for each 21-day cycle for up to 8 cycles.
Phase1: Dose-escalation Phase: Labetuzumab Govitecan (LG) Once Weekly Dosing	Labetuzumab Govitecan (LG)	Participants will receive 8, 12 and 16 mg/dose of LG once weekly dosing until unacceptable toxicity, progressive disease or death whichever occurs first, for each 21-day cycle for up to up to 8 cycles, with a contingency to examine intermediate dose levels of 10 or 14 mg/kg, or if necessary to a lower dose level of 6 mg/kg.
Phase1: Dose-escalation Phase: LG Twice Weekly Dosing	Labetuzumab Govitecan (LG)	Participants will receive 6 and 9 mg/kg per dose twice weekly dose of LG until unacceptable toxicity, progressive disease or death whichever occurs first, for each 21-day cycle for up to up to 8 cycles. A lower dose level of 4 mg/kg may be added if \> 1 out of 3 or 2 out of 6 participants are unable to tolerate all 4 doses without dose delay or reduction.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Adverse Events and Serious Adverse Events (SAEs)	From first dose date up to approximately 2 years after the last dose or until disease progression
Percentage of Participants With Laboratory Abnormalities	From first dose date up to approximately 2 years after the last dose or until disease progression

Secondary Outcome Measures

Name	Time	Method
Progression-free Survival	From first dose date up to 12 weeks post treatment (Up to approximately 2 years after the last dose or until disease progression)	Progression free survival (PFS) is defined as the interval from the start of study drug treatment to the earlier of the first documentation of disease progression or death from any cause.
Change from Baseline in Carcinoembryonic Antigen (CEA) Serum Levels	From first dose date up to approximately 2 years after the last dose or until disease progression
Duration of Response	From first documentation of PR or CR to the earlier of the first documentation of PD or death from any cause (Up to approximately 2 years after the last dose or until disease progression)	Duration of response (DOR) is defined as the interval from the first documentation of PR or CR to the earlier of the first documentation of disease progression (PD) or death from any cause.
Time-to-treatment Failure	From first dose date up to 8 treatment cycles (each cycle = 21 days) (Up to approximately 24 weeks)	Time to treatment failure (TTF) is defined as the interval from the start of treatment to the earlier of the first documentation of disease progression or death due to any cause, the permanent cessation of LG therapy due to all reasons except progressive disease, participant died or lost to follow up.
Time to Progression	From first dose of study treatment up to PD (Up to approximately 2 years after the last dose or until disease progression)	Time to progression is defined as the interval from the first dose of treatment to the first documentation of disease progression (PD).
Overall Survival	From first dose date up to approximately 2 years	Overall survival is defined as the time from start of study drug treatment to death from any cause.

Trial Locations

Locations (7)

Vanderbilt-Ingram Cancer Center; 🇺🇸 Nashville, Tennessee, United States

Helen F. Graham Cancer Center-Christiana Care; 🇺🇸 Newark, Delaware, United States

The Ohio State University Comprehensive Cancer Center; 🇺🇸 Columbus, Ohio, United States

IUHealth Goshen Center for Cancer Care; 🇺🇸 Goshen, Indiana, United States

Fox Chase; 🇺🇸 Philadelphia, Pennsylvania, United States

UCLA Jonsson Comprehensive Cancer Center; 🇺🇸 Santa Monica, California, United States

University of Colorado Anschutz Medical Campus; 🇺🇸 Aurora, Colorado, United States