An Investigational Immuno-therapy Study of Nivolumab, and Nivolumab in Combination With Other Anti-cancer Drugs, in Colon Cancer That Has Come Back or Has Spread - Full Text View

Purpose

The purpose of this study is to examine if Nivolumab by itself, or Nivolumab in combination with other anti-cancer drugs, will result in meaningful tumor size reduction, in patients with colon cancer that has come back or has spread, and who have a specific biomarker in their tumors.

Condition	Intervention	Phase
Microsatellite Unstable Colorectal Cancer Microsatellite Stable Colorectal Cancer Mismatch Repair Proficient Colorectal Cancer Mismatch Repair Deficient Colorectal Cancer	Drug: Ipilimumab Drug: Nivolumab Drug: Cobimetinib Drug: Daratumumab Drug: anti-LAG-3 antibody	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: No masking Primary Purpose: Treatment
Official Title:	A Phase 2 Clinical Trial of Nivolumab, or Nivolumab Combinations in Recurrent and Metastatic Microsatellite High (MSI-H) and Non-MSI-H Colon Cancer

Resource links provided by NLM:

Drug Information available for: Nivolumab

U.S. FDA Resources

Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:

Objective response rate (ORR) in all MSI-High and non-MSI-High subjects as determined by Investigators [ Time Frame: The final analysis of the primary endpoint will occur at least 6 months after the last enrolled subject's first dose of study therapy (Approximately up to 34 months) ]
(Tumor imaging assessments will occur every 6 weeks from the date of first dose (+/-1 wk) for the first 24 weeks, then every 12 wks (+/- 1 wk) thereafter until disease progression or treatment is discontinued (whichever occurs later)) (Tumor imaging assessments will occur every 6 weeks from the date of first dose (+/-1 wk) for the first 24 weeks, then every 12 wks (+/- 1 wk) thereafter until disease progression or treatment is discontinued (whichever occurs later))

Secondary Outcome Measures:

ORR in all MSI-H and non-MSI-H subjects based on IRRC determination [ Time Frame: The final analysis of the secondary endpoint will occur the time of the primary endpoint analysis (Approximately up to 34 months) ]
Tumor imaging assessments will occur every 6 weeks from the date of first dose (+/- wk) for the first 24 weeks, then every 12 wks (+/- 1 wk) thereafter until disease progression or treatment is discontinued(whichever occurs later)


Estimated Enrollment:	340
Actual Study Start Date:	March 7, 2014
Estimated Study Completion Date:	December 31, 2019
Estimated Primary Completion Date:	March 11, 2018 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Nivolumab Monotherapy Nivolumab administered as IV infusion at a dose of 3mg/kg every 2 weeks until disease progression	Drug: Nivolumab Other Names: BMS-936558 Opdivo
Experimental: Nivolumab (Nivo) + Ipilimumab (Ipi) Nivo 3mg/Kg IV with Ipi 1 mg/Kg IV every 3 week (wk) for 4 doses followed by Nivo 3mg/Kg IV every 2wk until progression Dose Escalation Phase: (Complete) Dose Level (DL) 1: Nivo 0.3mg/Kg with Ipi 1 mg/Kg IV every 3wk for 4 doses followed by Nivo 3mg/Kg IV every 2wk until progression DL 1: Nivo 1mg/Kg IV with Ipi 1 mg/Kg IV every 3 wk for 4 doses followed by Nivo 3mg/Kg IV every 2wk until progression DL 2a: Nivo 1mg/Kg IV with Ipi 3 mg/Kg IV every 3wk for 4 doses followed by Nivo 3mg/Kg IV every 2 wk until progression DL 2b: Nivo 3mg/Kg IV with Ipi 1 mg/Kg IV every 3wk for 4 doses followed by Nivo 3mg/Kg IV every 2 wk until progression	Drug: Ipilimumab Other Name: Yervoy Drug: Nivolumab Other Names: BMS-936558 Opdivo
Experimental: Nivolumab (Nivo) + Ipilimumab (Ipi) Cohort C3 Nivo IV dosed every 2wk with Ipi IV dosed every 6wk.	Drug: Ipilimumab Other Name: Yervoy Drug: Nivolumab Other Names: BMS-936558 Opdivo
Experimental: Nivolumab (Nivo) + Ipilimumab (Ipi) + Cobimetinib Cohort C4 Nivo IV dosed every 2wk, with Ipi IV dosed every 6wk, combined with Cobimetinib dosed orally once daily 21 days on/7 days off.	Drug: Ipilimumab Other Name: Yervoy Drug: Nivolumab Other Names: BMS-936558 Opdivo Drug: Cobimetinib Other Name: Cotellic
Experimental: Nivolumab (Nivo) + BMS-986016 Cohort C5 Nivo IV dosed every 2wk with BMS-986016 dosed every 2 wk	Drug: Nivolumab Other Names: BMS-936558 Opdivo Drug: anti-LAG-3 antibody Other Name: BMS-986016
Experimental: Nivolumab (Nivo) + Daratumumab Cohort C6 Daratumumab IV dosed weekly for week 1-8; then every 2 wks from Week 9-24; then every 4 wks on week 25; with Nivo dosed every 2 wks starting at week 3 and every 4 wks starting at week 25	Drug: Nivolumab Other Names: BMS-936558 Opdivo Drug: Daratumumab Other Name: Darzalex

Detailed Description:

Allocation: The Microsatellite Instability High (MSI-High) and C4 and C6 Cohort Parts of the trial are Non-randomized, The Non-MSI high Dose Escalation Phase part of the trial contained a randomized portion

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

Men and women ≥ 18 years of age
Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
Histologically confirmed recurrent or metastatic colorectal cancer
Measurable disease by CT or MRI
Testing for MSI Status (by an accredited lab)
1. Subjects with microsatellite instability high (MSI-H) tumors will enroll in the MSI-H Cohort (mStage and cStage groups), the C3 Cohort, and the C5 Cohort.
2. Subjects with phenotypes that are non-microsatellite instability high (non-MSI-H) will enroll in the non- MSI-H Safety Cohort and the C6, C4 Cohorts.
Adequate organ function as defined by study-specific laboratory tests
Must use acceptable form of birth control throughout the study. After the final dose of study drug, an acceptable form of birth control must be used for 23 weeks for women of childbearing potential (WOCBP) and 31 weeks for men who are sexually active with WOCBP
Signed informed consent
Willing and able to comply with study procedures
Subjects enrolled into the C3 Cohort must have not had treatment for their metastatic disease

Exclusion Criteria:

Active brain metastases or leptomeningeal metastases are not allowed.
Prior treatment with an anti-Programmed Death Receptor (PD)-1, anti-PD-L1, anti-PD-L2, anti-Cytotoxic T-Cell Lymphoma-4 Antigen (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
Prior malignancy active within the previous 3 years except for locally curable cancers
Subjects with active, known or suspected autoimmune disease
Subjects with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of study drug administration

Other protocol defined inclusion/exclusion criteria could apply

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02060188

Contacts


Contact: Recruiting sites have contact information. Please contact the sites directly. If there is no contact information, please email:		Clinical.Trials@bms.com
Contact: First line of the email MUST contain NCT# and Site #.

Hide Study Locations

Locations


United States, Arizona
Banner MD Anderson Cancer Center	Recruiting
Gilbert, Arizona, United States, 85234
Contact: Tomislav Dragovich, Site 0028 480-256-3429
United States, California
USC Norris Comprehensive Cancer Center	Recruiting
Los Angeles, California, United States, 90033
Contact: Heinz-Josef Lenz, Site 0004 323-865-0820
Pacific Hematology Oncology Associates	Recruiting
San Francisco, California, United States, 94115
Contact: Ari Baron, Site 0001 415-600-1775
United States, Georgia
Emory University	Recruiting
Atlanta, Georgia, United States, 30322
Contact: Bassel El-Rayes, Site 0008 404-778-1900
United States, Massachusetts
Dana Faber Cancer Institute	Recruiting
Boston, Massachusetts, United States, 02114
Contact: Jeffrey Clark, Site 0036 617-632-5960
Massachusetts General Hospital	Recruiting
Boston, Massachusetts, United States, 02114
Contact: Jeffrey Clark, Site 0002 617-724-9347
United States, Minnesota
Allina Health System	Recruiting
Minneapolis, Minnesota, United States, 55407
Contact: Joseph Leach, Site 0034 612-863-5658
United States, North Carolina
Duke University Office of Research Administration	Recruiting
Durham, North Carolina, United States, 27710
Contact: Michael Morse, Site 0024 919-668-1861
Novant Health Oncology Specialists	Recruiting
Winston-Salem, North Carolina, United States, 27103
Contact: Franklin Chen, Site 0029 336-718-8461
United States, Oregon
Providence Cancer Center Oncology and Hematology Care- Eastside	Recruiting
Portland, Oregon, United States, 97213
Contact: Todd Crocenzi, Site 0005 503-215-2855
United States, Pennsylvania
Lehigh Valley Hospital	Recruiting
Allentown, Pennsylvania, United States, 18103
Contact: Usman Shah, Site 0041 610-402-9543
University Of Pittsburgh Cancer Institute	Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: James Lee, Site 0013 412-623-2677
United States, Tennessee
Vanderbilt University Med Ctr	Recruiting
Nashville, Tennessee, United States, 37232-0021
Contact: Emily Chan, Site 0006 615-936-5847
United States, Texas
Md Anderson Can Cnt	Recruiting
Houston, Texas, United States, 77030-4009
Contact: Michael Overman, Site 0003 713-563-7757
Australia, New South Wales
Local Institution	Not yet recruiting
Camperdown, New South Wales, Australia, 2050
Contact: Site 0038
Local Institution	Recruiting
Westmead, New South Wales, Australia, 2145
Contact: Site 0040
Australia, Queensland
Tasman Oncology Research Pty Ltd	Recruiting
Southport, Queensland, Australia, 4215
Contact: , Site 0039 +61411518959
Australia, Victoria
Local Institution	Recruiting
Parkville, Victoria, Australia, 3050
Contact: Site 0037
Belgium
Local Institution	Recruiting
Brussels, Belgium, 1000
Contact: Site 0019
Local Institution	Recruiting
Brussels, Belgium, 1090
Contact: Site 0018
Local Institution	Recruiting
Leuven, Belgium, 3000
Contact: Site 0020
Canada, Alberta
Cross Cancer Institute	Recruiting
Edmonton, Alberta, Canada, T6G 1Z2
Contact: Michael Sawyer, Site 0027
Canada, Ontario
Princess Margaret Hospital	Recruiting
Toronto, Ontario, Canada, M5G 1X5
Contact: Albiruni Razak, Site 0016 4169464501
France
Local Institution	Recruiting
Paris, France, 75012
Contact: Site 0025
Ireland
Local Institution	Recruiting
Dublin 4, Ireland
Contact: Site 0022
Local Institution	Recruiting
Dublin 9, Ireland
Contact: Site 0023
Local Institution	Recruiting
Galway, Ireland
Contact: Site 0033
Italy
Local Institution	Recruiting
Candiolo, TO, Italy, 10060
Contact: Site 0030
Local Institution	Recruiting
Modena, Italy, 41124
Contact: Site 0035
Local Institution	Recruiting
Padova, Italy, Padova
Contact: Site 0032
Spain
Local Institution	Recruiting
Madrid, Spain, 28009
Contact: Site 0012
Local Institution	Recruiting
Madrid, Spain, 28050
Contact: Site 0010
Local Institution	Recruiting
Sevilla, Spain, 41013
Contact: Site 0011

Sponsors and Collaborators

Bristol-Myers Squibb

Investigators


Study Director:	Bristol-Myers Squibb	Bristol-Myers Squibb

More Information

Additional Information:

BMS Clinical Trial Information This link exits the ClinicalTrials.gov site

FDA Safety Alerts and Recalls This link exits the ClinicalTrials.gov site

BMS Clinical Trial Patient Recruiting This link exits the ClinicalTrials.gov site

Investigator Inquiry Form This link exits the ClinicalTrials.gov site


Responsible Party:	Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT02060188 History of Changes
Other Study ID Numbers:	CA209-142 2013-003939-30 ( EudraCT Number )
Study First Received:	December 18, 2013
Last Updated:	June 26, 2017


Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

Additional relevant MeSH terms:


Colorectal Neoplasms Colonic Neoplasms Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Digestive System Diseases Gastrointestinal Diseases Colonic Diseases	Intestinal Diseases Rectal Diseases Antibodies Antibodies, Monoclonal Nivolumab Daratumumab Immunologic Factors Physiological Effects of Drugs Antineoplastic Agents

ClinicalTrials.gov processed this record on July 17, 2017

An Investigational Immuno-therapy Study of Nivolumab, and Nivolumab in Combination With Other Anti-cancer Drugs, in Colon Cancer That Has Come Back or Has Spread (CheckMate142)