A Phase II Study of the Safety and Efficacy of E7820 Plus Cetuximab in Colorectal Cancer, Preceded by a Run-in Study in Advanced Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT00309179
First received: March 29, 2006
Last updated: December 6, 2012
Last verified: December 2012
  Purpose

This study proposes to determine the safety of the administration of E7820 plus cetuximab and explore the MTD of the combination in a Phase Ib study. In addition, the efficacy of this combination will be explored in patients with colorectal cancer in the Phase II proof of concept phase of the study.


Condition Intervention Phase
Advanced Colorectal Cancer
Drug: E7820 plus cetuximab
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Single Arm Phase II Study of the Efficacy, Safety, and Biomarkers of Activity of E7820 Plus Cetuximab in Advanced Solid Tumors Preceded by a Run-In Study to Determine Safety of the Combination

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • Objective tumor response (CR or PR) and disease control (CR, PR or SD) rates will be evaluated in this study based on RECIST criteria and modified WHO criteria. [ Time Frame: The timing will be based on RECIST criteria and modified WHO criteria. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetics: Blood samples will be taken on Days 1, 2, and 15 during Cycle 1 and Day 1. Pharmacodynamics: Blood will be taken prior to dosing on Day 1, Days 1, 2, and 15 during Cycle 1 and Day 1. [ Time Frame: Days 1, 2, and 15 during Cycle 1 and Day 1. ] [ Designated as safety issue: Yes ]

Enrollment: 99
Study Start Date: August 2006
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: E7820 plus cetuximab
Escalating doses from 40 mg/m^2 irinotecan plus E7820 in combination with cetuximab.

  Eligibility

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

Inclusion Criteria:

  • For Phase Ib, patients must have a histologically or cytologically confirmed malignant solid tumor for which no effective therapy is available or the patient must not be a candidate for standard therapy.
  • For Phase II, patients must have a pathologically and histologically documented colorectal carcinoma that is inoperable and/or metastatic. These patients must also have at least one unidimensional measurable lesion according to the RECIST guidelines.
  • Patients must have an ECOG Performance Status of 0-1.
  • Patients must have a life expectancy of >= 3 months.
  • Patients must be aged >= 18 years.
  • Patients must have adequate renal function as evidenced by serum creatinine < 2 mg/dL and creatinine clearance > 40 mL/minute.
  • Patients must have adequate bone marrow function as evidenced by ANC >= 1,500 /mm3 and platelets >= 100,000 /mm3.
  • Patients must have adequate hepatic function as evidenced by liver function test abnormalities no greater than CTC grade 1 (bilirubin, alanine transaminase [ALT], and aspartate transaminase [AST]) unless increased LFTs are related to liver metastases in which case CTC grade 2 abnormalities acceptable.
  • Patients must be willing and able to comply with the study protocol for the duration of the study.
  • Patients must give written informed consent prior to any study-specific screening procedures with the understanding that the patient may withdraw consent at any time without prejudice.
  • Patients may have received prior bevacizumab therapy as long as therapy has been discontinued for 4 weeks or longer.

Exclusion Criteria:

  • Patients who have a history of previous Grade 2 or higher hypersensitivity to sulfonamide derivatives.
  • Patients previously treated with cetuximab, or who have received prior treatment with any EGFR-related cancer therapy, either an approved or investigational agent.
  • Patients with known sensitivity to murine monoclonal antibodies.
  • Patients who have had radiation to >= 25% of their bone marrow (e.g., pelvic radiation) within 4 weeks prior to E7820 treatment.
  • Patients who have not recovered from any clinically significant (Grade 3 or 4) chemotherapy, immunotherapy, or radiotherapy related toxicity at study entry (excluding neuropathy, infertility, or alopecia).
  • Patients who have received investigational drugs or any other anti-neoplastic therapy within 28 days of E7820 treatment.
  • Patients who have had major surgery within 4 weeks of study drug administration.
  • Women who are pregnant or breast-feeding. Women of childbearing potential with either a positive pregnancy test at screening or no pregnancy test. Women of childbearing potential unless using adequate measures of contraception in the opinion of the Investigator (postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential).
  • Fertile men and fertile women who are not willing to use contraception or fertile men or fertile women with a partner who is not willing to use contraception.
  • Patients with brain or subdural metastases are not eligible except if they have completed local therapy and have discontinued the use of corticosteroids for this indication for at least one month before starting treatment with E7820. Any signs (eg, radiologic) and/or symptoms from their brain metastases must be stable for at least one month.
  • Patients who have a positive history of human immunodeficiency virus, hepatitis B or active hepatitis C.
  • Patients with severe uncontrolled intercurrent illness/infection (excluding malignancies).
  • Patients with a history of unstable ischemic cardiac disease or more than Class II NYHA heart failure.
  • Patients with a history of clinically significant arterial thrombosis or who have taken therapeutic doses of anticoagulants within the last 7 days.
  • Patients who have pulmonary disease that puts them at risk of hemoptysis or bleeding diathesis. Head and neck cancer patients at risk for major vessel bleeding.
  • Patients receiving therapeutics doses of anticoagulants.
  • Patients with poorly controlled type I insulin-dependent diabetes or poorly-controlled type II insulin-dependent diabetes or a fasting blood glucose >10 mmol/L (200 mg/dL).
  • Patients with significant comorbid disease or condition, which in the Investigator's opinion would exclude the patient from the study.
  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: NCT00309179

Locations
United States, California
Los Angeles, California, United States
United States, Florida
Miami, Florida, United States
Canada, Alberta
Edmonton, Alberta, Canada
Sponsors and Collaborators
Eisai Inc.
Investigators
Study Director: Eisai Medical Services Eisai Inc.
  More Information

No publications provided

Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT00309179     History of Changes
Other Study ID Numbers: E7820-A001-204
Study First Received: March 29, 2006
Last Updated: December 6, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Eisai Inc.:
Advanced colorectal cancer

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
Cetuximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 02, 2014