Study of CS-7017 in Combination With FOLFIRI in Subjects With Metastatic Colorectal Cancer Who Failed First-Line Therapy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo Inc.
ClinicalTrials.gov Identifier:
NCT00967616
First received: August 27, 2009
Last updated: May 7, 2014
Last verified: May 2014
  Purpose

This phase 2, randomized, active-controlled, open-label, parallel group, multicenter study will be conducted at up to 18 study centers in the US, Central America, and South America. Adult subjects with metastatic colorectal cancer (CRC) who failed first-line chemotherapy will participate in the study, which will be conducted on an outpatient basis. It is anticipated that 100 subjects will be enrolled to obtain approximately 90 evaluable subjects.


Condition Intervention Phase
Colorectal Cancer
Neoplasms, Colorectal
Drug: CS7017
Drug: irinotecan, leucovorin, and 5-fluorouracil (5-FU) (FOLFIRI)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized, Active-Controlled, Open-Label Phase 2 Study of CS-7017 in Combination With FOLFIRI in Subjects With Metastatic Colorectal Cancer Who Failed First-Line Therapy

Resource links provided by NLM:


Further study details as provided by Daiichi Sankyo Inc.:

Primary Outcome Measures:
  • Estimate difference between proportion of subjects with progression free survival (PFS) who failed first-line chemotherapy and treated with combination of CS-7017/irinotecan, leucovorin, and 5-fluorouracil (5-FU) (FOLFIRI) or FOLFIRI alone. [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To determine progression free survival, overall survival, objective response rate, duration of objective response. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 100
Study Start Date: September 2009
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CS7017 plus FOLFIRI
CS7017 plus irinotecan, leucovorin, and 5-fluorouracil (5-FU) (FOLFIRI)
Drug: CS7017
CS-7017 (0.25mg tablet) Two CS-7017 tablets will be administered PO BID every 12 hours. FOLFIRI will be administered IV once every 2 weeks.
Drug: irinotecan, leucovorin, and 5-fluorouracil (5-FU) (FOLFIRI)

FOLFIRI will be administered IV once every 2 weeks.

The FOLFIRI regimen consists of:

  • 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
  • 5-FU, 1200 mg/m2/day x 2 days (total 2400 mg/m2 over 46 to 48 hours continuous infusion)
Other Names:
  • Irinotecan
  • Leucovorin
  • 5-FU
  • 5-fluorouracil
Active Comparator: FOLFIRI
irinotecan, leucovorin, and 5-fluorouracil (5-FU) (FOLFIRI)
Drug: irinotecan, leucovorin, and 5-fluorouracil (5-FU) (FOLFIRI)

FOLFIRI will be administered IV once every 2 weeks.

The FOLFIRI regimen consists of:

  • 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
  • 5-FU, 1200 mg/m2/day x 2 days (total 2400 mg/m2 over 46 to 48 hours continuous infusion)
Other Names:
  • Irinotecan
  • Leucovorin
  • 5-FU
  • 5-fluorouracil

  Eligibility

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

Inclusion Criteria:

  • Metastatic CRC that has progressed following first-line therapy.
  • Measurable disease (Response Evaluation Criteria in Solid Tumors [RECIST], Version 1.0.34.
  • Male or female = 18 years of age.
  • Eastern Cooperative Oncology Group (ECOG) performance status = 2.
  • Resolution of any toxic effects of prior therapy (except alopecia) to NCI CTCAE, Version 3.0, grade = 1.
  • Adequate organ and bone marrow function as evidenced by:

    • Hemoglobin = 9 g/dL (transfusion and/or growth factor support allowed)
    • Absolute neutrophil count (ANC) = 1.5 x 109/L
    • Platelet count = 100 x 109/L Serum creatinine = 1.5 x the upper limit of normal (ULN) or creatinine clearance = 60 mL/min
    • Aspartate aminotransferase (AST) and alkaline phosphatase = 2.5 x ULN in subjects with no liver metastasis and = 5.0 x ULN in subjects with liver metastasis
    • Total bilirubin = 1.5 x ULN
  • Women of childbearing potential must be willing to consent to using effective contraception (eg, hormonal contraceptives, bilateral tubal ligation, barrier with spermicide, intrauterine device) while on treatment and for at least 3 months thereafter. Men who are the partner of a woman of childbearing potential must be willing to consent to using effective contraception (e.g., vasectomy or barrier with spermicide) while on treatment and for 3 months thereafter.
  • All female subjects of childbearing potential must have a negative pregnancy test (serum or urine) result before initiating 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 IEC- or IRB-approved ICF (including HIPAA authorization, if applicable) before performance of any study-specific procedures or tests.
  • Subjects must be willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria:

  • First-line treatment with an irinotecan-based regimen (eg, FOLFIRI).
  • Anticipation of need for a major surgical procedure or radiation therapy (RT) during the study.
  • Treatment with chemotherapy, other TZDs, RT, surgery, immunotherapy, biological therapy, or any investigational anticancer agent within 4 weeks before start of study treatment.
  • History of any of the following conditions within 6 months before initiating study treatment:

    • Diabetes mellitus requiring treatment with insulin or TZD agents
    • Myocardial infarction with significant impairment of cardiac function (e.g., ejection fraction = 50%)
    • Severe/unstable angina pectoris
    • Coronary/peripheral artery bypass graft
    • New York Heart Association (NYHA) class III or IV congestive heart failure
    • Malabsorption syndrome, chronic diarrhea (lasting > 4 weeks), inflammatory bowel disease, or partial bowel obstruction.
  • Subjects with clinically active brain metastases (defined as untreated, symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms); uncontrolled seizure disorder; spinal cord compression; or carcinomatous meningitis. Subjects with treated brain metastasis will be included in the study if they have recovered from the acute, toxic effects of RT. A minimum of 15 days must have elapsed between the end of RT and enrollment into the study.
  • History of malignancy other than CRC, unless there is an 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, severe, active infection requiring IV antibiotic or antiviral agents.
  • Pericardial or pleural effusion (eg, requiring drainage) or pericardial involvement with the tumor. Subjects with minimal pleural effusion may be eligible upon request by Investigator and approval by Sponsor.
  • Need for concomitant use of other TZDs during the study.
  • Previous administration of CS-7017.
  • Pregnant or breast feeding.
  • Known to be homozygous for the UGT1A1*28 allele.
  • Known history of severe hypersensitivity reactions to any of the components of CS-7017, irinotecan, leucovorin, or 5-FU.
  • 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.
  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: NCT00967616

Locations
United States, California
Beverly Hills Cancer Center
Beverly Hills, California, United States, 90211
St. Jude Heritage Medical Group
Fullerton, California, United States, 92835
United States, District of Columbia
John Marshall
Washington, District of Columbia, United States, 20007
United States, Georgia
Georgia Cancer Specialists
Atlanta, Georgia, United States, 30341
United States, Maryland
Victor Priego
Bethesda, Maryland, United States, 20817
United States, Ohio
Gabrail Cancer Center
Canton, Ohio, United States, 44718
Argentina
Instituto FIDES Oncologia y Especialidades Medicas
Buenos Aires, Argentina, B1900BAJ
CAIPO Centro para la Atencion Integral del Paciente Oncologico
Tucuman, Argentina, T4000GTB
Brazil
Hospital Sao Lucas da Pontificia Universidade Catolica do Rio Grande do Sul - PUC-RS
Porto Alegre, Brazil, 90610-000
Instituto Nacional de Cancer INCA
Rio de Janeiro, Brazil, 20231-050
ICAVC
Sao Paulo, Brazil, 01209-000
Chile
Instituto Nacional del Cancer
Santiago, Chile, 8380455
Fundacion Arturo Lopez Perez
Santiago, Chile, 8320000
Instituto Oncologico Clinica Renaca
Vina del Mar, Chile, 2540364
Peru
Hospital Nacional Alberto Sabogai Sologuren
Callao, Peru
Hospital Nacional Dos de Mayo
Lima, Peru, 01
Oncosalud SAC
Lima, Peru, 41
Hospital Nacional Dos de Mayo
Lima, Peru
Sponsors and Collaborators
Daiichi Sankyo Inc.
  More Information

No publications provided

Responsible Party: Daiichi Sankyo Inc.
ClinicalTrials.gov Identifier: NCT00967616     History of Changes
Other Study ID Numbers: CS7017-A-U203
Study First Received: August 27, 2009
Last Updated: May 7, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Daiichi Sankyo Inc.:
metastatic
colon
rectum
combination
chemotherapy

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

ClinicalTrials.gov processed this record on September 18, 2014