Clinical trial NCT01605318: Study of Labetuzumab Govitecan in Participants With Metastatic Colorectal Cancer
Official title: A Phase I/II Study of Once or Twice Weekly IMMU-130 (hMN-14-SN38, Antibody-Drug Conjugate) in Patients With Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Metastatic Colorectal Cancer
Colon Cancer
Rectal Cancer
Keywords: Previously treated Metastatic colorectal cancer
Previously treated Colon cancer
Previously treated Rectal cancer
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2012-05-24
Enrollment: 92
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 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With Adverse Events and Serious Adverse Events (SAEs)
timeFrame: From first dose date up to approximately 2 years after the last dose or until disease progression
measure: Percentage of Participants With Laboratory Abnormalities
timeFrame: From first dose date up to approximately 2 years after the last dose or until disease progression
Secondary outcomes:
measure: Duration of Response
timeFrame: 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)
measure: Progression-free Survival
timeFrame: From first dose date up to 12 weeks post treatment (Up to approximately 2 years after the last dose or until disease progression)
measure: Time to Progression
timeFrame: From first dose of study treatment up to PD (Up to approximately 2 years after the last dose or until disease progression)
measure: Overall Survival
timeFrame: From first dose date up to approximately 2 years
measure: Time-to-treatment Failure
timeFrame: From first dose date up to 8 treatment cycles (each cycle = 21 days) (Up to approximately 24 weeks)
measure: Change from Baseline in Carcinoembryonic Antigen (CEA) Serum Levels
timeFrame: From first dose date up to approximately 2 years after the last dose or until disease progression
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: UCLA Jonsson Comprehensive Cancer Center
state: California
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus
state: Colorado
city: Newark
country: United States
facility: Helen F. Graham Cancer Center-Christiana Care
state: Delaware
city: Goshen
country: United States
facility: IUHealth Goshen Center for Cancer Care
state: Indiana
city: Columbus
country: United States
facility: The Ohio State University Comprehensive Cancer Center
state: Ohio
city: Philadelphia
country: United States
facility: Fox Chase
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: Govindan SV, Goldenberg DM. New antibody conjugates in cancer therapy. ScientificWorldJournal. 2010 Oct 12;10:2070-89. doi: 10.1100/tsw.2010.191.
citation: 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.
citation: 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.
citation: 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.
citation: 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.