Study of Labetuzumab Govitecan in Participants With Metastatic Colorectal Cancer

NCT ID: NCT01605318

Last Updated: 2024-01-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

92 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-02-12

Study Completion Date

2017-01-03

Brief Summary

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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

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Conditions

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Metastatic Colorectal Cancer Colon Cancer Rectal Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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

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.

Group Type EXPERIMENTAL

Labetuzumab Govitecan (LG)

Intervention Type DRUG

Administered as a slow intravenous (IV) infusion.

Phase1: Dose-escalation Phase: LG Twice Weekly Dosing

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.

Group Type EXPERIMENTAL

Labetuzumab Govitecan (LG)

Intervention Type DRUG

Administered as a slow intravenous (IV) infusion.

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

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.

Group Type EXPERIMENTAL

Labetuzumab Govitecan (LG)

Intervention Type DRUG

Administered as a slow intravenous (IV) infusion.

Interventions

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Labetuzumab Govitecan (LG)

Administered as a slow intravenous (IV) infusion.

Intervention Type DRUG

Other Intervention Names

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hMN14-SN38 Labetuzumab-SN38 Antibody-Drug Conjugate IMMU-0130 GS-0130

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

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UCLA Jonsson Comprehensive Cancer Center

Santa Monica, California, United States

Site Status

University of Colorado Anschutz Medical Campus

Aurora, Colorado, United States

Site Status

Helen F. Graham Cancer Center-Christiana Care

Newark, Delaware, United States

Site Status

IUHealth Goshen Center for Cancer Care

Goshen, Indiana, United States

Site Status

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status

Fox Chase

Philadelphia, Pennsylvania, United States

Site Status

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

Countries

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United States

References

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Govindan SV, Goldenberg DM. New antibody conjugates in cancer therapy. ScientificWorldJournal. 2010 Oct 12;10:2070-89. doi: 10.1100/tsw.2010.191.

Reference Type BACKGROUND
PMID: 20953556 (View on PubMed)

Govindan SV, Cardillo TM, Moon SJ, Hansen HJ, Goldenberg DM. CEACAM5-targeted therapy of human colonic and pancreatic cancer xenografts with potent labetuzumab-SN-38 immunoconjugates. Clin Cancer Res. 2009 Oct 1;15(19):6052-61. doi: 10.1158/1078-0432.CCR-09-0586. Epub 2009 Sep 29.

Reference Type BACKGROUND
PMID: 19789330 (View on PubMed)

Moon SJ, Govindan SV, Cardillo TM, D'Souza CA, Hansen HJ, Goldenberg DM. Antibody conjugates of 7-ethyl-10-hydroxycamptothecin (SN-38) for targeted cancer chemotherapy. J Med Chem. 2008 Nov 13;51(21):6916-26. doi: 10.1021/jm800719t. Epub 2008 Oct 22.

Reference Type BACKGROUND
PMID: 18939816 (View on PubMed)

Govindan SV, Griffiths GL, Hansen HJ, Horak ID, Goldenberg DM. Cancer therapy with radiolabeled and drug/toxin-conjugated antibodies. Technol Cancer Res Treat. 2005 Aug;4(4):375-91. doi: 10.1177/153303460500400406.

Reference Type BACKGROUND
PMID: 16029057 (View on PubMed)

Dotan E, Cohen SJ, Starodub AN, Lieu CH, Messersmith WA, Simpson PS, Guarino MJ, Marshall JL, Goldberg RM, Hecht JR, Wegener WA, Sharkey RM, Govindan SV, Goldenberg DM, Berlin JD. Phase I/II Trial of Labetuzumab Govitecan (Anti-CEACAM5/SN-38 Antibody-Drug Conjugate) in Patients With Refractory or Relapsing Metastatic Colorectal Cancer. J Clin Oncol. 2017 Oct 10;35(29):3338-3346. doi: 10.1200/JCO.2017.73.9011. Epub 2017 Aug 17.

Reference Type BACKGROUND
PMID: 28817371 (View on PubMed)

Other Identifiers

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IMMU-130-02

Identifier Type: -

Identifier Source: org_study_id

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