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

NCT00967616 | Completed Phase 2 Results

• 1 other identifier: CS7017-A-U203
• Study Type: interventional
• Target: 100
• Locations: 5 countries
• Sites: 18

Brief Summary

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.

Conditions

Colorectal Cancer; Neoplasms, Colorectal

Keywords

metastatic; colon; rectum; combination; chemotherapy

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Progression-Free Survival at 16 Weeks After Administration of CS-7017 Combined With Irinotecan, Leucovorin, and 5-Fluorouracil (5-FU) After Failure of First-line Therapy in Treatment of Metastatic Colorectal Cancer

  Progression-free survival (PFS) was defined as the time from randomization until the first objective evidence of disease progression or death from any cause.

  Baseline to 16 weeks postdose

Secondary Outcomes (4)

• Median Overall Progression-Free Survival Following Administration of CS-7017 in Combination With Irinotecan, Leucovorin, and 5-Fluorouracil (5-FU) (FOLFIRI) After Failure of First-line Therapy in Treatment of Metastatic Colorectal Cancer

  Baseline to approximately 3 years postdose

• Median Overall Progression-Free Survival: Sensitivity Analysis Including Clinical Progression After Administration of CS-7017 and Irinotecan, Leucovorin, and 5-Fluorouracil After Failure of First-line Therapy of Metastatic Colorectal Cancer

  Baseline to approximately 3 years postdose

• Best Overall Response and Objective Response Rate Following Administration of CS-7017 in Combination With Irinotecan, Leucovorin, and 5-Fluorouracil (FOLFIRI) After Failure of First-line Therapy in Treatment of Metastatic Colorectal Cancer

  Baseline to approximately 3 years postdose

• Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following Administration of CS-7017 Combined With Irinotecan, Leucovorin, and 5-Fluorouracil (FOLFIRI) After Failure of First-line Therapy in Treatment of Metastatic Colorectal Cancer

  Baseline to 30 days post last dose, up to approximately 3 years

Study Arms (2)

FOLFIRI

ACTIVE COMPARATOR

Participants who received irinotecan, leucovorin, and 5-fluorouracil (5-FU) (FOLFIRI). FOLFIRI was administered by intravenous (IV) injection once every 2 weeks. The FOLFIRI regimen consisted of: * Irinotecan, 180 mg/m\^2 IV infusion over 30 to 120 minutes * Leucovorin, 400 mg/m\^2 IV infusion to match the duration of the irinotecan infusion * 5-FU, 1200 mg/m\^2/day x 2 days (total 2400 mg/m\^2 over 46 to 48 hours continuous infusion)

Drug: irinotecan, leucovorin, and 5-fluorouracil (5-FU) (FOLFIRI)

CS7017+FOLFIRI

EXPERIMENTAL

Participants who received CS7017 plus irinotecan, leucovorin, and 5-fluorouracil (5-FU) (FOLFIRI). Two CS-7017 tablets were administered by mouth (PO) twice a day (BID) every 12 hours. FOLFIRI was administered IV once every 2 weeks. The FOLFIRI regimen consisted of: * Irinotecan, 180 mg/m\^2 IV infusion over 30 to 120 minutes * Leucovorin, 400 mg/m\^2 IV infusion to match the duration of the irinotecan infusion * 5-FU, 1200 mg/m\^2/day x 2 days (total 2400 mg/m\^2 over 46 to 48 hours continuous infusion)

Drug: CS7017; Drug: irinotecan, leucovorin, and 5-fluorouracil (5-FU) (FOLFIRI)

Interventions

CS7017 DRUG

CS-7017 (0.25mg tablet) Two CS-7017 tablets will be administered by mouth (PO) BID every 12 hours. FOLFIRI will be administered IV once every 2 weeks.

CS7017+FOLFIRI

irinotecan, leucovorin, and 5-fluorouracil (5-FU) (FOLFIRI) DRUG

FOLFIRI will be administered IV once every 2 weeks. The FOLFIRI regimen consists of: * Irinotecan, 180 mg/m\^2 IV infusion over 30 to 120 minutes * Leucovorin, 400 mg/m\^2 IV infusion to match the duration of the irinotecan infusion * 5-FU, 1200 mg/m\^2/day x 2 days (total 2400 mg/m\^2 over 46 to 48 hours continuous infusion)

Also known as: Irinotecan, Leucovorin, 5-FU, 5-fluorouracil

CS7017+FOLFIRI; FOLFIRI

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Metastatic CRC that has progressed following first-line therapy.
• Measurable disease (Response Evaluation Criteria in Solid Tumors \[RECIST\], Version 1.0.
• 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 10\^9/L
• Platelet count ≥ 100 x 10\^9/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 participants with no liver metastasis and ≤ 5.0 x ULN in participants 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 (eg, vasectomy or barrier with spermicide) while on treatment and for 3 months thereafter.
• All female participants of childbearing potential must have a negative pregnancy test (serum or urine) result before initiating study treatment.
• Participants 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 Independent Ethics Committee (IEC)- or Institutional Review Board (IRB)-approved informed consent form (ICF) (including HIPAA authorization, if applicable) before performance of any study-specific procedures or tests.

You may not qualify if:

• 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 thiazolidinediones (TZD), 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 (eg, 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.
• Participants 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. Participants 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. Participants with minimal pleural effusion may be eligible upon request by Investigator and approval by Sponsor.
• Need for concomitant use of other TZD agents during the study.

Sponsors & Collaborators

• Daiichi Sankyo: lead

Study Sites (18)

Beverly Hills Cancer Center

Beverly Hills, California, 90211, United States

Location

St. Jude Heritage Medical Group

Fullerton, California, 92835, United States

Location

John Marshall

Washington D.C., District of Columbia, 20007, United States

Location

Georgia Cancer Specialists

Atlanta, Georgia, 30341, United States

Location

Victor Priego

Bethesda, Maryland, 20817, United States

Location

Gabrail Cancer Center

Canton, Ohio, 44718, United States

Location

Instituto FIDES Oncologia y Especialidades Medicas

Buenos Aires, B1900BAJ, Argentina

Location

CAIPO Centro para la Atencion Integral del Paciente Oncologico

San Miguel de Tucumán, T4000GTB, Argentina

Location

Hospital Sao Lucas da Pontificia Universidade Catolica do Rio Grande do Sul - PUC-RS

Porto Alegre, 90610-000, Brazil

Location

Instituto Nacional de Cancer INCA

Rio de Janeiro, 20231-050, Brazil

Location

ICAVC

São Paulo, 01209-000, Brazil

Location

Fundacion Arturo Lopez Perez

Santiago, 8320000, Chile

Location

Instituto Nacional del Cancer

Santiago, 8380455, Chile

Location

Instituto Oncologico Clinica Renaca

Viña del Mar, 2540364, Chile

Location

Hospital Nacional Alberto Sabogai Sologuren

Callao, Peru

Location

Hospital Nacional Dos de Mayo

Lima, 01, Peru

Location

Oncosalud SAC

Lima, 41, Peru

Location

Hospital Nacional Dos de Mayo

Lima, Peru

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasm Metastasis

Interventions

efatutazone; Irinotecan; Leucovorin; Fluorouracil

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Contact for Clinical Trial Information
• Organization: Daiichi Sankyo

CTRinfo@dsi.com

908-992-6400

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2009
• First Posted: August 28, 2009
• Study Start: September 1, 2009
• Primary Completion: April 1, 2013
• Study Completion: April 1, 2013
• Last Updated: May 4, 2020
• Results First Posted: May 4, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.

Locations

CL (3); BR (3); PE (4); US (6); AR (2)