CClinicalTrials.gg
TerminatedNCT03368859Updated Feb 9, 2021Results posted

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

A Phase 2 interventional study of Leucovorin and Fluorouracil - bolus in Cancer, sponsored by AbbVie. Terminated at 65 sites in 6 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-02-09.

Sponsored by AbbVie · Phase 2, Interventional, and Treatment

Why this study was terminated
Study may continue
Phase
Phase 2
Study type
Interventional
Enrollment
70
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

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.

02

Conditions studied

  • Cancer

Keywords

  • cancer
  • colorectal cancer
  • ABT-165
  • FOLFIRI
  • Bevacizumab
  • bowel cancer
  • metastatic colorectal cancer
  • metastatic colorectal
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
70 participants (actual)

Study arms

  • Experimental
    ABT-165 plus FOLFIRI

    ABT-165 plus FOLFIRI (irinotecan, leucovorin, fluorouracil).

    Drug: Leucovorin · Drug: Fluorouracil - bolus · Drug: Fluorouracil - infusion · Drug: ABT-165 · Drug: Irinotecan

  • Active comparator
    Bevacizumab plus FOLFIRI

    Bevacizumab plus FOLFIRI (irinotecan, leucovorin, fluorouracil).

    Drug: Leucovorin · Drug: Fluorouracil - bolus · Drug: Bevacizumab · Drug: Fluorouracil - infusion · Drug: Irinotecan

Interventions

  • DrugLeucovorin

    Intravenous

    Also known as: Folinic Acid

  • DrugFluorouracil - bolus

    Intravenous

    Also known as: 5-FU

  • DrugBevacizumab

    Intravenous

    Also known as: Avastin

  • DrugFluorouracil - infusion

    Intravenous

    Also known as: 5-FU

  • DrugABT-165

    Intravenous

  • DrugIrinotecan

    Intravenous

    Also known as: Irinotecan hydrochloride

05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: 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 outcomes

  1. 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.

    Time frame: 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

  2. Overall Survival (OS)

    OS is defined as the time from randomization until death from any cause.

    Time frame: 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

06

Results

Posted Feb 9, 2021

Participant flow

The intent to treat (ITT) population included all randomized participants and was used for all efficacy and baseline analyses.

Participant flow — Overall Study
MilestoneABT-165 Plus FOLFIRIBevacizumab Plus FOLFIRI
Started3634
Completed00
Not completed3634
Withdrew: Withdrew consent54
Withdrew: Death126
Withdrew: Study terminated by sponsor1823
Withdrew: Other11

Outcome measures

PrimaryProgression 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.

Time frame:
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
Reported as:
Median · Months
Progression Free Survival (PFS)
MonthsABT-165 Plus FOLFIRIBevacizumab Plus FOLFIRI
Progression Free Survival (PFS)3.78 (2.07 to 7.20)7.36 (5.68 to 10.55)
SecondaryObjective 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.

Time frame:
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
Reported as:
Number · percentage of participants
Objective Response Rate (ORR)
percentage of participantsABT-165 Plus FOLFIRIBevacizumab Plus FOLFIRI
Objective Response Rate (ORR)5.6 (0.7 to 18.7)14.7 (5.0 to 31.1)
SecondaryOverall Survival (OS)

OS is defined as the time from randomization until death from any cause.

Time frame:
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
Reported as:
Median · Months
Overall Survival (OS)
MonthsABT-165 Plus FOLFIRIBevacizumab Plus FOLFIRI
Overall Survival (OS)7.95 (7.00 to NA)NA (10.55 to NA)

Adverse events

Collected over Adverse events were collected from first dose of study drug to 90 days (+15 days) after the last dose and then every 90 days (+15 days) throughout the survival period;the median duration across both treatment groups was 38.6 (3.0-99.3) weeks.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
ABT-165 Plus FOLFIRI12/34 (35.3%)17/34 (50%)32/34 (94.1%)
Bevacizumab Plus FOLFIRI6/32 (18.8%)8/32 (25%)31/32 (96.9%)
Most frequent serious events
Showing 10 of 32
Most frequent serious events
EventABT-165 Plus FOLFIRIBevacizumab Plus FOLFIRI
MALIGNANT NEOPLASM PROGRESSIONNeoplasms benign, malignant and unspecified (incl cysts and polyps)3/342/32
FEBRILE NEUTROPENIABlood and lymphatic system disorders2/341/32
INTESTINAL PERFORATIONGastrointestinal disorders2/340/32
SEPSISInfections and infestations2/340/32
ANAL HAEMORRHAGEGastrointestinal disorders0/341/32
GASTRIC PERFORATIONGastrointestinal disorders0/341/32
DISEASE PROGRESSIONGeneral disorders0/341/32
BILE DUCT STENOSISHepatobiliary disorders0/341/32
CELLULITISInfections and infestations0/341/32
HEPATITIS BInfections and infestations0/341/32
Most frequent other events
Showing 10 of 70
Most frequent other events
EventABT-165 Plus FOLFIRIBevacizumab Plus FOLFIRI
DIARRHOEAGastrointestinal disorders18/3415/32
NAUSEAGastrointestinal disorders18/3414/32
NEUTROPENIABlood and lymphatic system disorders14/3412/32
FATIGUEGeneral disorders14/3413/32
STOMATITISGastrointestinal disorders7/3410/32
HYPERTENSIONVascular disorders10/344/32
VOMITINGGastrointestinal disorders5/349/32
CONSTIPATIONGastrointestinal disorders8/345/32
DECREASED APPETITEMetabolism and nutrition disorders8/347/32
DIZZINESSNervous system disorders7/342/32

Baseline characteristics

Age, Continuous
Age, Continuous(years)ABT-165 Plus FOLFIRIBevacizumab Plus FOLFIRITotal
Mean60.8 ± 11.4160.2 ± 10.1960.5 ± 10.76
Sex: Female, Male
Sex: Female, Male(Participants)ABT-165 Plus FOLFIRIBevacizumab Plus FOLFIRITotal
Female151530
Male211940
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)ABT-165 Plus FOLFIRIBevacizumab Plus FOLFIRITotal
Hispanic or Latino235
Not Hispanic or Latino343165
Unknown or Not Reported000
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)ABT-165 Plus FOLFIRIBevacizumab Plus FOLFIRITotal
White202040
Black or African American213
Asian111122
American Indian or Alaska native101
Native Hawaiian or other Pacific Islander101
Missing123
07

Study locations

65 sites
  • Ironwood Cancer & Res Ctr /ID# 200044
    Chandler, Arizona 85224-5665, United States
  • Highlands Oncology Group /ID# 169289
    Fayetteville, Arkansas 72703-4005, United States
  • City of Hope /ID# 200501
    Duarte, California 91010, United States
  • St. Joseph Heritage Healthcare /ID# 200100
    Fullerton, California 92835, United States
  • USC Norris Cancer Center /ID# 200410
    Los Angeles, California 90033, United States
  • Hoag Memorial Hosp Presbyterian /ID# 202661
    Newport Beach, California 92663, United States
  • Torrance Health Association (DBA)Torrance Memorial Physician Network/Cancer Care /ID# 202488
    Redondo Beach, California 90277-3036, United States
  • UC Davis Comprehensive Cancer Center - Main /ID# 207227
    Sacramento, California 95817, United States
  • Pacific Central Coast Health Centers-SLO Oncology and Hematology Health Center /ID# 201215
    San Luis Obispo, California 93401-7068, United States
  • Central Coast Medical Oncology /ID# 200227
    Santa Maria, California 93454-5909, United States
  • University of California, Los /ID# 169294
    Santa Monica, California 90404, United States
  • Kaiser Permanente, Waterpark III Institute for Health Research /ID# 200801
    Aurora, Colorado 80014, United States
  • Georgetown University Hospital /ID# 202903
    Washington, District of Columbia 20007, United States
  • Florida Cancer Specialist - South /ID# 203796
    Fort Myers, Florida 33901-8108, United States
  • Florida Cancer Specialists-Panhandle /ID# 203787
    Tallahassee, Florida 32308-5304, United States
  • IACT Health /ID# 169292
    Columbus, Georgia 31904-8946, United States
  • Ingalls Memorial Hosp /ID# 169892
    Harvey, Illinois 60426, United States
  • Illinois Cancer Care, PC /ID# 202189
    Peoria, Illinois 61615, United States
  • Fort Wayne Medical Oncology /ID# 201616
    Fort Wayne, Indiana 46804, United States
  • Cancer Center of Kansas /ID# 200627
    Wichita, Kansas 67214, United States
  • Norton Cancer Institute /ID# 200674
    Louisville, Kentucky 40207, United States
  • Ochsner Clinic Foundation-New Orleans /ID# 169291
    New Orleans, Louisiana 70121, United States
  • Whiteside Institute for Clinic /ID# 200802
    Duluth, Minnesota 55805, United States
  • Mmcorc /Id# 202099
    Saint Louis Park, Minnesota 55416, United States
  • Washington University School /ID# 200621
    Saint Louis, Missouri 63108, United States
  • University of Nebraska /ID# 203195
    Omaha, Nebraska 68198, United States
  • The Valley Hospital /ID# 169999
    Paramus, New Jersey 07652, United States
  • Duke University Medical Center /ID# 169657
    Durham, North Carolina 27710-3000, United States
  • Fairview Hospital - Moll Pavilion /ID# 205910
    Cleveland, Ohio 44111-5605, United States
  • Cleveland Clinic Main Campus /ID# 200325
    Cleveland, Ohio 44195, United States
  • Hillcrest Hospital /ID# 205911
    Mayfield Heights, Ohio 44124, United States
  • INTEGRIS Cancer Institute of OK/INTEGRIS Southwest Medical Center /ID# 200831
    Oklahoma City, Oklahoma 73109-3411, United States
  • INTEGRIS Cancer Institute /ID# 200832
    Oklahoma City, Oklahoma 73142, United States
  • Oregon Health and Science University /ID# 170807
    Portland, Oregon 97239, United States
  • Thomas Jefferson University /ID# 200833
    Philadelphia, Pennsylvania 19107-4414, United States
  • UPMC Hillman Cancer Ctr /ID# 200672
    Pittsburgh, Pennsylvania 15232, United States
  • Greenville Hospital System /ID# 203021
    Greenville, South Carolina 29605, United States
  • Tennessee Oncology-Nashville Centennial /ID# 203424
    Nashville, Tennessee 37203-1632, United States
  • Tennessee Oncology, PLLC /ID# 203581
    Nashville, Tennessee 37203, United States
  • Ut Southwestern Medical Center /Parkland Health and Hospital System /Id# 210112
    Dallas, Texas 75235-7709, United States
  • UTSW-Dallas /ID# 204031
    Dallas, Texas 75390, United States
  • Millennium Oncology /ID# 204925
    Houston, Texas 77090-1243, United States
  • Virginia Cancer Specialists /ID# 169293
    Fairfax, Virginia 22031, United States
  • Kadlec Clinic Hematology and O /ID# 170811
    Kennewick, Washington 99336, United States
  • Medical Oncology Associates /ID# 169290
    Spokane, Washington 99208, United States
  • Univ of Wisconsin Hosp/Clinics /ID# 200424
    Madison, Wisconsin 53792-0001, United States
  • UZ Gent /ID# 200691
    Gent, Oost-Vlaanderen 9000, Belgium
  • Imelda Ziekenhuis /ID# 200693
    Bonheiden, 2820, Belgium
  • Cliniques universitaires Saint /ID# 203101
    Brussels, 1200, Belgium
  • UZ Antwerp /ID# 200694
    Edegem, 2650, Belgium
  • UZ Leuven /ID# 200001
    Leuven, 3000, Belgium
  • Hospital Maisonneuve-Rosemont /ID# 171590
    Montreal, Quebec H1T 2M4, Canada
  • Jewish General Hospital /ID# 171584
    Montreal, Quebec H3T 1E2, Canada
  • National Cancer Center /ID# 170879
    Goyang, Gyeonggido 10408, Korea, Republic of
  • Samsung Medical Center /ID# 170875
    Seoul, Seoul Teugbyeolsi 06351, Korea, Republic of
  • Seoul National University Hospital /ID# 170878
    Seoul, 03080, Korea, Republic of
  • Asan Medical Center /ID# 170877
    Seoul, 05505, Korea, Republic of
  • Hospital Universitario Vall d'Hebron /ID# 200186
    Barcelona, 08035, Spain
  • Hospital General Universitario Gregorio Maranon /ID# 200189
    Madrid, 28007, Spain
  • Hospital Clinico Universitario San Carlos /ID# 201721
    Madrid, 28040, Spain
  • Hospital Universitario Fundacion Jimenez Diaz /ID# 200187
    Madrid, 28040, Spain
  • Hospital Universitario HM Sanchinarro /ID# 200190
    Madrid, 28050, Spain
  • National Taiwan Univ Hosp /ID# 170677
    Taipei City, Taipei 10002, Taiwan
  • Taichung Veterans General Hosp /ID# 170123
    Taichung City, 40705, Taiwan
  • Taipei Veterans General Hosp /ID# 170675
    Taipei City, 11217, Taiwan
08

References and documents

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. PubMed 35920133 ↗

Study documents

  • Protocol and statistical analysis plan · Feb 7, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — 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.

Supporting information: Study protocol, Sap, Csr

09

Registry details

Key details

Study ID
NCT03368859
Lead sponsor
AbbVie
Responsible party
Sponsor
First posted
Dec 11, 2017
Start date
Mar 20, 2018
Primary completion
Dec 18, 2019
Completion
Dec 18, 2019
Results posted
Feb 9, 2021
Last update
Feb 9, 2021

Study contacts

AbbVie Inc.
study director · AbbVie

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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