Study of Labetuzumab Govitecan in Participants With Metastatic Colorectal Cancer

Gilead Sciences

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Metastatic Colorectal Cancer; Colon Cancer; Rectal Cancer

Treatments: Drug: Labetuzumab Govitecan (LG)

Study type: Interventional

Funder types: Industry

Identifiers

NCT01605318

IMMU-130-02

Details and patient eligibility

About

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.

Enrollment: 92 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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92 participants in 3 patient groups

Phase1: Dose-escalation Phase: Labetuzumab Govitecan (LG) Once Weekly Dosing

Experimental group

Description:

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.

Treatment:

Drug: Labetuzumab Govitecan (LG)

Phase1: Dose-escalation Phase: LG Twice Weekly Dosing

Experimental group

Description:

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.

Treatment:

Drug: Labetuzumab Govitecan (LG)

Phase 2: Dose-expansion Phase: LG Once or Twice Weekly Dosing

Experimental group

Description:

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.

Treatment:

Drug: Labetuzumab Govitecan (LG)