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Efficacy and Safety of Simtuzumab (SIM) With FOLFIRI as Second Line Treatment in Colorectal Adenocarcinoma

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ClinicalTrials.gov Identifier: NCT01479465
Recruitment Status : Terminated
First Posted : November 24, 2011
Results First Posted : April 17, 2019
Last Update Posted : April 17, 2019
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Tracking Information
First Submitted Date  ICMJE November 9, 2011
First Posted Date  ICMJE November 24, 2011
Results First Submitted Date  ICMJE March 26, 2019
Results First Posted Date  ICMJE April 17, 2019
Last Update Posted Date April 17, 2019
Actual Study Start Date  ICMJE December 2011
Actual Primary Completion Date October 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 26, 2019)
Progression Free Survival (PFS) [ Time Frame: Randomization up to 27 months ]
The PFS was defined as the time from the date of randomization to the earliest event time of: a) death regardless of cause, or b) first indication of disease progression. PFS was analyzed using Kaplan-Meier (KM) estimates.
Original Primary Outcome Measures  ICMJE
 (submitted: November 22, 2011)
Progression Free Survival [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months. ]
Change History Complete list of historical versions of study NCT01479465 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 26, 2019)
  • Overall Survival (OS) [ Time Frame: Randomization up to 33 months ]
    The OS is measured as time from date of randomization to death regardless of cause. The OS was analyzed using KM estimates.
  • Objective Response Rate (ORR) [ Time Frame: Randomization up to 27 months ]
    Objective response was assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria (version 1.1) as Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD). The ORR was defined as the percentage of participants who achieved a CR or PR.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of Simtuzumab (SIM) With FOLFIRI as Second Line Treatment in Colorectal Adenocarcinoma
Official Title  ICMJE A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of GS-6624 Combined With FOLFIRI as Second Line Treatment for Metastatic KRAS Mutant Colorectal Adenocarcinoma That Has Progressed Following a First Line Oxaliplatin- and Fluoropyrimidine-Containing Regimen
Brief Summary The primary objective of this study is to compare the additive efficacy of SIM versus placebo in combination with leucovorin (folinic acid), irinotecan, and fluorouracil (FOLFIRI) as measured by improvement in progression-free survival (PFS) in participants with metastatic KRAS mutant colorectal adenocarcinoma who have progressed following a first-line oxaliplatin- and fluoropyrimidine-containing regimen.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Colorectal Cancer
Intervention  ICMJE
  • Biological: Simtuzumab
    SIM administered via intravenous infusion over 30 minutes
    Other Name: SIM; GS-6624
  • Drug: Placebo to match SIM
    Placebo to match SIM administered via intravenous infusion over 30 minutes
  • Drug: Leucovorin
    l-Leucovorin 200 mg/m^2 or dl-leucovorin 400 mg/m^2 administered via intravenous infusion over 2 hours
    Other Name: Folinic acid
  • Drug: Irinotecan
    Irinotecan 180 mg/m^2 administered via intravenous infusion over 90 minutes
  • Drug: Fluorouracil
    Fluorouracil 400 mg/m^2 administered via intravenous bolus and 2400 mg/m^2 via intravenous infusion over 46 hours
Study Arms  ICMJE
  • Experimental: FOLFIRI + SIM 700 mg (Part A)
    Participants will receive SIM 700 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
    Interventions:
    • Biological: Simtuzumab
    • Drug: Leucovorin
    • Drug: Irinotecan
    • Drug: Fluorouracil
  • Experimental: FOLFIRI + SIM 200 mg (Part B)
    Participants will receive SIM 200 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
    Interventions:
    • Biological: Simtuzumab
    • Drug: Leucovorin
    • Drug: Irinotecan
    • Drug: Fluorouracil
  • Experimental: FOLFIRI + SIM 700 mg (Part B)
    Participants will receive SIM 700 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
    Interventions:
    • Biological: Simtuzumab
    • Drug: Leucovorin
    • Drug: Irinotecan
    • Drug: Fluorouracil
  • Experimental: FOLFIRI + Placebo (Part B)
    Participants will receive placebo to match SIM via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
    Interventions:
    • Drug: Placebo to match SIM
    • Drug: Leucovorin
    • Drug: Irinotecan
    • Drug: Fluorouracil
Publications * Hecht JR, Benson AB 3rd, Vyushkov D, Yang Y, Bendell J, Verma U. A Phase II, Randomized, Double-Blind, Placebo-Controlled Study of Simtuzumab in Combination with FOLFIRI for the Second-Line Treatment of Metastatic KRAS Mutant Colorectal Adenocarcinoma. Oncologist. 2017 Mar;22(3):243-e23. doi: 10.1634/theoncologist.2016-0479. Epub 2017 Feb 28.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: September 16, 2014)
266
Original Estimated Enrollment  ICMJE
 (submitted: November 22, 2011)
265
Actual Study Completion Date  ICMJE February 2015
Actual Primary Completion Date October 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Metastatic colorectal carcinoma with KRAS mutation
  • Received first line therapy and discontinued part or all of first line therapy
  • Estimated life expectancy > 3 months
  • Stage IV disease
  • Eastern Cooperative Oncology Group (ECOG) performance status: 0-2
  • Adequate hepatic and hematologic function
  • No major operations within 4 weeks prior to treatment start

Exclusion Criteria:

  • More than 1 prior chemotherapy regimen for Stage 4 colorectal cancer
  • Experimental medical treatment within 30 days prior to study entry
  • Known or suspected cerebral metastases
  • History or presence of any form of cancer, other that colorectal cancer, within the 3 years prior to enrollment
  • Known dihydropyrimidine dehydrogenase-deficiency (special screening not required)
  • Subjects with angina pectoris, poorly controlled ventricular arrhythmias (does not include asymptomatic, occasional premature ventricular contractions), history of clinically significant coronary heart disease or cardiomyopathy, or electrocardiogram (ECG) abnormalities consistent with ischemia
  • Uncontrolled hypertension (seated systolic blood pressure > 180 mm Hg or diastolic blood pressure > 110 mm Hg) at screening
  • Clinically active liver disease, including active hepatitis (any etiology) or cirrhosis
  • Anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy, retinoid therapy, hormonal therapy) within 21 days prior to randomization
  • Prior irinotecan therapy for metastatic disease is not permitted
  • Systemic fungal, bacterial, viral, or other infection

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States,   France,   Germany,   Italy,   Poland,   Russian Federation,   Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01479465
Other Study ID Numbers  ICMJE GS-US-295-0203
2011-003754-61 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Gilead Sciences
Study Sponsor  ICMJE Gilead Sciences
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Zung Thai, MD Gilead Sciences
PRS Account Gilead Sciences
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP