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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

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.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Biological: Simtuzumab Drug: Placebo to match SIM Drug: Leucovorin Drug: Irinotecan Drug: Fluorouracil Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 266 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : December 2011
Actual Primary Completion Date : October 2014
Actual Study Completion Date : February 2015

Arm Intervention/treatment
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.
Biological: Simtuzumab
SIM administered via intravenous infusion over 30 minutes
Other Name: SIM; GS-6624

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

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.
Biological: Simtuzumab
SIM administered via intravenous infusion over 30 minutes
Other Name: SIM; GS-6624

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

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.
Biological: Simtuzumab
SIM administered via intravenous infusion over 30 minutes
Other Name: SIM; GS-6624

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

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.
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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.



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

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01479465


  Show 109 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Zung Thai, MD Gilead Sciences

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01479465     History of Changes
Other Study ID Numbers: GS-US-295-0203
2011-003754-61 ( EudraCT Number )
First Posted: November 24, 2011    Key Record Dates
Results First Posted: April 17, 2019
Last Update Posted: April 17, 2019
Last Verified: March 2019
Keywords provided by Gilead Sciences:
GSI
Gilead
Gilead Sciences
GS-6624
Colorectal Cancer
KRAS
Oncology
monoclonal antibody
Additional relevant MeSH terms:
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Colorectal Neoplasms
Adenocarcinoma
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Irinotecan
Fluorouracil
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs