A Study of ABT-165 Plus FOLFIRI vs Bevacizumab Plus FOLFIRI in Subjects With Metastatic Colorectal Cancer Previously Treated With Fluoropyrimidine, Oxaliplatin and Bevacizumab

Phase 2 Study Comparing Efficacy and Safety of ABT-165 Plus FOLFIRI vs Bevacizumab Plus FOLFIRI in Metastatic Colorectal Cancer Previously Treated With Fluoropyrimidine, Oxaliplatin and Bevacizumab

A study to evaluate the efficacy and tolerability of ABT-165 plus FOLFIRI compared to bevacizumab plus FOLFIRI in participants with previously treated metastatic adenocarcinoma of the colon or rectum.

Study Overview

• Status: Terminated
• Conditions: Cancer
• Intervention / Treatment: Drug: Irinotecan; Drug: Leucovorin; Drug: Bevacizumab; Drug: Fluorouracil - bolus; Drug: Fluorouracil - infusion; Drug: ABT-165

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Bonheiden, Belgium, 2820
    • Imelda Ziekenhuis /ID# 200693
  • Brussels, Belgium, 1200
    • Cliniques universitaires Saint /ID# 203101
  • Edegem, Belgium, 2650
    • UZ Antwerp /ID# 200694
  • Leuven, Belgium, 3000
    • UZ Leuven /ID# 200001
  • Oost-Vlaanderen
    • Gent, Oost-Vlaanderen, Belgium, 9000
      • UZ Gent /ID# 200691
• Canada
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • Hospital Maisonneuve-Rosemont /ID# 171590
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital /ID# 171584
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital /ID# 170878
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center /ID# 170877
  • Gyeonggido
    • Goyang, Gyeonggido, Korea, Republic of, 10408
      • National Cancer Center /ID# 170879
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 06351
      • Samsung Medical Center /ID# 170875
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron /ID# 200186
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Maranon /ID# 200189
  • Madrid, Spain, 28040
    • Hospital Clinico Universitario San Carlos /ID# 201721
  • Madrid, Spain, 28040
    • Hospital Universitario Fundacion Jimenez Diaz /ID# 200187
  • Madrid, Spain, 28050
    • Hospital Universitario HM Sanchinarro /ID# 200190
• Taiwan
  • Taichung City, Taiwan, 40705
    • Taichung Veterans General Hosp /ID# 170123
  • Taipei City, Taiwan, 11217
    • Taipei Veterans General Hosp /ID# 170675
  • Taipei
    • Taipei City, Taipei, Taiwan, 10002
      • National Taiwan Univ Hosp /ID# 170677
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224-5665
      • Ironwood Cancer & Res Ctr /ID# 200044
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703-4005
      • Highlands Oncology Group /ID# 169289
  • California
    • Duarte, California, United States, 91010
      • City of Hope /ID# 200501
    • Fullerton, California, United States, 92835
      • St. Joseph Heritage Healthcare /ID# 200100
    • Los Angeles, California, United States, 90033
      • USC Norris Cancer Center /ID# 200410
    • Newport Beach, California, United States, 92663
      • Hoag Memorial Hosp Presbyterian /ID# 202661
    • Redondo Beach, California, United States, 90277-3036
      • Torrance Health Association (DBA)Torrance Memorial Physician Network/Cancer Care /ID# 202488
    • Sacramento, California, United States, 95817
      • UC Davis Comprehensive Cancer Center - Main /ID# 207227
    • San Luis Obispo, California, United States, 93401-7068
      • Pacific Central Coast Health Centers-SLO Oncology and Hematology Health Center /ID# 201215
    • Santa Maria, California, United States, 93454-5909
      • Central Coast Medical Oncology /ID# 200227
    • Santa Monica, California, United States, 90404
      • University of California, Los /ID# 169294
  • Colorado
    • Aurora, Colorado, United States, 80014
      • Kaiser Permanente, Waterpark III Institute for Health Research /ID# 200801
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Hospital /ID# 202903
  • Florida
    • Fort Myers, Florida, United States, 33901-8108
      • Florida Cancer Specialist - South /ID# 203796
    • Tallahassee, Florida, United States, 32308-5304
      • Florida Cancer Specialists-Panhandle /ID# 203787
  • Georgia
    • Columbus, Georgia, United States, 31904-8946
      • IACT Health /ID# 169292
  • Illinois
    • Harvey, Illinois, United States, 60426
      • Ingalls Memorial Hosp /ID# 169892
    • Peoria, Illinois, United States, 61615
      • Illinois Cancer Care, PC /ID# 202189
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Fort Wayne Medical Oncology /ID# 201616
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas /ID# 200627
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Norton Cancer Institute /ID# 200674
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic Foundation-New Orleans /ID# 169291
  • Minnesota
    • Duluth, Minnesota, United States, 55805
      • Whiteside Institute for Clinic /ID# 200802
    • Saint Louis Park, Minnesota, United States, 55416
      • Mmcorc /Id# 202099
  • Missouri
    • Saint Louis, Missouri, United States, 63108
      • Washington University School /ID# 200621
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska /ID# 203195
  • New Jersey
    • Paramus, New Jersey, United States, 07652
      • The Valley Hospital /ID# 169999
  • North Carolina
    • Durham, North Carolina, United States, 27710-3000
      • Duke University Medical Center /ID# 169657
  • Ohio
    • Cleveland, Ohio, United States, 44111-5605
      • Fairview Hospital - Moll Pavilion /ID# 205910
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Main Campus /ID# 200325
    • Mayfield Heights, Ohio, United States, 44124
      • Hillcrest Hospital /ID# 205911
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73109-3411
      • INTEGRIS Cancer Institute of OK/INTEGRIS Southwest Medical Center /ID# 200831
    • Oklahoma City, Oklahoma, United States, 73142
      • INTEGRIS Cancer Institute /ID# 200832
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University /ID# 170807
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107-4414
      • Thomas Jefferson University /ID# 200833
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Hillman Cancer Ctr /ID# 200672
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Greenville Hospital System /ID# 203021
  • Tennessee
    • Nashville, Tennessee, United States, 37203-1632
      • Tennessee Oncology-Nashville Centennial /ID# 203424
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology, PLLC /ID# 203581
  • Texas
    • Dallas, Texas, United States, 75235-7709
      • Ut Southwestern Medical Center /Parkland Health and Hospital System /Id# 210112
    • Dallas, Texas, United States, 75390
      • UTSW-Dallas /ID# 204031
    • Houston, Texas, United States, 77090-1243
      • Millennium Oncology /ID# 204925
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists /ID# 169293
  • Washington
    • Kennewick, Washington, United States, 99336
      • Kadlec Clinic Hematology and O /ID# 170811
    • Spokane, Washington, United States, 99208
      • Medical Oncology Associates /ID# 169290
  • Wisconsin
    • Madison, Wisconsin, United States, 53792-0001
      • Univ of Wisconsin Hosp/Clinics /ID# 200424

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of histologically or cytologically confirmed metastatic adenocarcinoma of the colon or rectum.

  • Primary tumor has been resected > 3 months prior to randomization.
• At least 1 lesion on a computed tomography (CT) scan (preferred) or magnetic resonance imaging (MRI) that is measurable as defined by Response Evaluation Criteria In Solid Tumors (RECIST), Version 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1.
• Progression following treatment with fluoropyrimidine/oxaliplatin/bevacizumab-regimen in the metastatic setting.
• Adequate hematologic, renal and hepatic function.

Exclusion Criteria:

• Any prior therapy with irinotecan
• Unresolved clinically significant toxicities from prior anticancer therapy, defined as any Common Terminology Criteria for Adverse Events (CTCAE) => Grade 2
• Clinically significant conditions that increase the risk for antiangiogenic therapy.
• History of any of the following during first-line therapy with a bevacizumab-containing regimen: arterial thrombotic/thromboembolic event, bowel perforation, Grade 4 hypertension, Grade 3 proteinuria or Grade 3 - 4 bleeding event.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: ABT-165 plus FOLFIRI; ABT-165 plus FOLFIRI (irinotecan, leucovorin, fluorouracil).	Drug: Irinotecan; Intravenous; Other Names: Irinotecan hydrochloride; Drug: Leucovorin; Intravenous; Other Names: Folinic Acid; Drug: Fluorouracil - bolus; Intravenous; Other Names: 5-FU; Drug: Fluorouracil - infusion; Intravenous; Other Names: 5-FU; Drug: ABT-165; Intravenous
ACTIVE_COMPARATOR: Bevacizumab plus FOLFIRI; Bevacizumab plus FOLFIRI (irinotecan, leucovorin, fluorouracil).	Drug: Irinotecan; Intravenous; Other Names: Irinotecan hydrochloride; Drug: Leucovorin; Intravenous; Other Names: Folinic Acid; Drug: Bevacizumab; Intravenous; Other Names: Avastin; Drug: Fluorouracil - bolus; Intravenous; Other Names: 5-FU; Drug: Fluorouracil - infusion; Intravenous; Other Names: 5-FU

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	PFS is defined as the time from randomization until the first occurrence of radiographic progression determined by investigator assessment or death from any cause.	Follow up continued until the first occurrence of radiographic progression, death from any cause or termination of the study; median follow-up time was 25.6(0.3-64.4) and 37.6(0.3-66.3) weeks in ABT-165 plus FOLFIRI and Bevacizumab + FOLFIRI, respectively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR is defined as the proportion of participants with a complete response (CR) or partial response (PR) as determined by a investigator assessment based on Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1.	From randomization up to 30 days after last dose of study drug; median time on follow-up was 25.6 (0.3 - 64.4) and 37.6 (0.3 - 66.3) weeks in ABT-165 plus FOLFIRI and Bevacizumab plus FOLFIRI, respectively
Overall Survival (OS)	OS is defined as the time from randomization until death from any cause.	Follow up continued until the first occurrence of radiographic progression, death from any cause or termination of the study; median follow-up time was 25.6(0.3-64.4) and 37.6(0.3-66.3) weeks in ABT-165 plus FOLFIRI and Bevacizumab + FOLFIRI, respectively

Collaborators and Investigators

• Sponsor: AbbVie

Publications and helpful links

General Publications

• Strickler JH, Cubillo A, Liang JT, Matrana M, Kozloff M, Lowe T, Blaney M, Sahtout M, Naumovski L, Wainberg ZA. Efficacy and safety of dilpacimab (ABT-165) versus bevacizumab plus FOLFIRI in metastatic colorectal cancer: a phase II study. Future Oncol. 2022 Sep;18(27):3011-3020. doi: 10.2217/fon-2021-1603. Epub 2022 Aug 3.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 20, 2018
• Primary Completion (ACTUAL): December 18, 2019
• Study Completion (ACTUAL): December 18, 2019

Study Registration Dates

• First Submitted: December 6, 2017
• First Submitted That Met QC Criteria: December 6, 2017
• First Posted (ACTUAL): December 11, 2017

Study Record Updates

• Last Update Posted (ACTUAL): February 9, 2021
• Last Update Submitted That Met QC Criteria: January 20, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: colorectal cancer; cancer; Bevacizumab; metastatic colorectal cancer; metastatic colorectal; FOLFIRI; bowel cancer; ABT-165
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Micronutrients; Vitamins; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Fluorouracil; Bevacizumab; Leucovorin; Irinotecan
• Other Study ID Numbers: M14-064; 2017-003669-87 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• IPD Sharing Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
• IPD Sharing Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No