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Study of CS-1008 in Combination With FOLFIRI in Patients Who Have Failed Other Treatments

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo Inc.
ClinicalTrials.gov Identifier:
NCT01124630
First received: May 10, 2010
Last updated: December 2, 2013
Last verified: December 2013
  Purpose

Treatment with CS-1008 in combination with FOLFIRI (irinotecan, leucovorin, and 5-fluorouracil [5-FU]) in subjects with metastatic colorectal cancer (CRC) who have failed first-line treatment that was not irinotecan-based.


Condition Intervention Phase
Metastatic Colorectal Cancer
Drug: CS-1008
Drug: FOLFIRI
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Study of CS-1008 in Combination With FOLFIRI (Irinotecan, Leucovorin, and 5-fluorouracil [5-FU]) in Subjects With Metastatic Colorectal Cancer (CRC) Who Have Failed First-line Treatment That Was Not Irinotecan-based.

Resource links provided by NLM:


Further study details as provided by Daiichi Sankyo Inc.:

Primary Outcome Measures:
  • Objective Response Rate [ Time Frame: up to 6 months ] [ Designated as safety issue: No ]
    To obtain a preliminary assessment of the antitumor activity of CS-1008 in combination with a FOLFIRI regimen based on the Objective Response Rate (ORR)

  • Progression Free Survival [ Time Frame: up to 6 months ] [ Designated as safety issue: No ]
    To obtain a preliminary assessment of the antitumor activity of CS-1008 in combination with a FOLFIRI regimen based on the Progression Free Survival (PFS)


Secondary Outcome Measures:
  • Serum concentrations [ Time Frame: weekly ] [ Designated as safety issue: No ]
    to determine serum concentrations at selected time intervals


Enrollment: 21
Study Start Date: May 2010
Study Completion Date: August 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CS-1008 with FOLFIRI
Experimental drug CS-1008 in combination with FOLFIRI
Drug: CS-1008
CS-1008 will be administered IV each week. The initial/loading dose (6 mg/kg) will be administered Day 1 of Cycle 1. Maintenance doses of 2 mg/kg will be administered weekly thereafter.
Drug: FOLFIRI
The FOLFIRI regimen will be administered IV at Weeks 1 and 3 of each 4 week cycle, and it will begin at Week 1 of Cycle 1. It will comprise irinotecan, 180 mg/m2 IV infusion over 30 to 120 minutes; leucovorin, 400 mg/m2 IV infusion to match the duration of the irinotecan infusion; and 5-FU, 400 mg/m2 (bolus) followed by 1200 mg/m2/day x 2 days (total 2400 mg/m2 over 46 to 48 hours continuous infusion).
Other Names:
  • FOLFIRI
  • irinotecan
  • leucovorin
  • 5-FU
  • Camptosar
  • Fluorouracil

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed, metastatic CRC that has progressed after first-line standard therapy that was not irinotecan-based.
  • At least 18 years of age.
  • Eastern Cooperative Oncology Group (ECOG) performance status of =< 2.
  • Adequate organ and bone marrow function as evidenced by:

    • Hemoglobin >= 9 g/dL
    • White blood cell count (WBC) >= 3.0 x 109/L
    • Absolute neutrophil count (ANC) >= 1.5 x 109/L
    • Platelet count >= 100 x 109/L
    • Serum creatinine < the upper limit of normal (ULN)
    • AST and alkaline phosphatase =< 2.5 x ULN if without liver metastasis and =< 5.0 x ULN if liver metastasis
    • Total bilirubin =< ULN
  • Male and female subjects of reproductive potential must be willing to consent to using effective contraception while on treatment and for 3 months after the end of treatment.
  • Female subjects of childbearing potential must have a negative pregnancy test (serum or urine) result within 8 days before starting study treatment.
  • Subjects must be fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible side effects) and must sign and date an IRB-approved ICF before performance of any study-specific procedures or tests.
  • At study centers located in the US, subjects must also sign a HIPAA authorization.
  • KRAS Mutant

Exclusion Criteria:

  • Anticipation of a need for a major surgical procedure or radiotherapy (RT) during the study.
  • Treatment with chemotherapy, hormonal therapy, RT, minor surgery, or any investigational agent within 4 weeks before study enrollment. Treatment with nitrosoureas, mitomycin C, immunotherapy, biological therapy, or major surgery within 6 weeks before study enrollment.
  • First-line therapy for CRC that was irinotecan-based.
  • History of any of the following conditions within 6 months before study enrollment:

    • Myocardial infarction;
    • Severe/unstable angina pectoris;
    • Coronary/peripheral artery bypass graft;
    • New York Heart Association (NYHA) class III or IV congestive heart failure;
    • Cerebrovascular accident or transient ischemic attack;
    • Pulmonary embolism or other clinically significant thromboembolic event; or
    • Clinically significant pulmonary disease (eg, severe chronic obstructive pulmonary disease or asthma).
  • Clinically active brain metastasis (ie, untreated, still requiring therapy with steroids or RT, or with progression within 4 weeks after completion of RT); an uncontrolled seizure disorder; spinal cord compression; or carcinomatous meningitis.
  • History of malignancy other than CRC, unless there is the expectation that the malignancy has been cured, and tumor-specific treatment for the malignancy has not been administered within the previous 5 years.
  • Clinically significant active infection that requires antibiotic therapy or Human Immunodeficiency Virus (HIV)-positive subjects receiving antiretroviral therapy.
  • Previous treatment with CS-1008, other agonistic DRSantibodies, or with TRAIL agonists.
  • If female, pregnant or breastfeeding.
  • Known history of hypersensitivity reactions to any of the components of CS-1008, irinotecan, leucovorin, or 5-FU formulations.
  • Serious intercurrent medical or psychiatric illnesses or any other conditions that in the opinion of the Investigator would impair the ability to give informed consent or unacceptably reduce protocol compliance or safety of the study treatment.
  • Must not be known to be homozygous for the UGT1A1*28 allele, as this increases the risk for neutropenia following irinotecan treatment.
  • Kras allele status must not be wild type.
  • Dihydropyrimidine dehydrogenase (DPD) deficiency.
  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: NCT01124630

Locations
United States, Arizona
Mayo Clinic
Scottsdale, Arizona, United States, 86259
United States, Florida
Mayo Clinic
Jacksonville, Florida, United States, 32224
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Daiichi Sankyo Inc.
  More Information

No publications provided

Responsible Party: Daiichi Sankyo Inc.
ClinicalTrials.gov Identifier: NCT01124630     History of Changes
Other Study ID Numbers: CS1008-A-U105
Study First Received: May 10, 2010
Last Updated: December 2, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Colorectal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Fluorouracil
Irinotecan
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses
Topoisomerase I Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on November 27, 2014