OSI-7904L and Oxaliplatin in Treating Patients With Refractory or Recurrent Advanced Colorectal Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier:
NCT00081237
First received: April 7, 2004
Last updated: June 11, 2013
Last verified: June 2013
  Purpose

RATIONALE: OSI-7904L may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy, such as oxaliplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining OSI-7904L with oxaliplatin may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of OSI-7904L and oxaliplatin in treating patients with refractory or recurrent advanced colorectal cancer.


Condition Intervention Phase
Colorectal Cancer
Drug: OSI-7904L
Drug: oxaliplatin
Phase 1

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of OSI-7904L In Combination With Oxaliplatin In Patients With Advanced Colo-Rectal Cancer

Resource links provided by NLM:


Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

Primary Outcome Measures:
  • Maximum tolerated dose and recommended dose for future trials as measured by CTC v3.0 [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Safety profile as measured by CTC v3.0 [ Designated as safety issue: Yes ]
  • Response as measured by RECIST every 6 weeks (2 courses) [ Designated as safety issue: No ]
  • Pharmacodynamics as measured by drug concentration in the blood during course 1 [ Designated as safety issue: No ]
  • Time to progression as measured by Kaplan Meier and RECIST every 6 weeks during treatment and then every 8 weeks [ Designated as safety issue: No ]

Enrollment: 15
Study Start Date: February 2004
Primary Completion Date: August 2005 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Determine the dose-limiting toxicity of OSI-7904L and oxaliplatin in patients with refractory or recurrent advanced colorectal cancer.
  • Determine the maximum tolerated dose of this regimen in these patients.
  • Determine a safe dose for this regimen in these patients.

Secondary

  • Determine the pharmacokinetic profile of this regimen in these patients.
  • Determine the safety profile of this regimen in these patients.
  • Determine the antitumor activity of this regimen in these patients.

OUTLINE: This is a nonrandomized, multicenter, open-label, dose-escalation study.

Patients receive oxaliplatin IV over 2 hours followed by OSI-7904L IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of OSI-7904L and oxaliplatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. A maximum of 12 patients receive treatment at the MTD.

Patients are followed every 8 weeks.

PROJECTED ACCRUAL: A total of 3-25 patients will be accrued for this study.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed colorectal cancer

    • Radiologic evidence of advanced disease
  • At least 1 measurable lesion at least 20 mm OR at least 10 mm by spiral CT scan

    • Indicator lesions in a previously irradiated field are allowed provided the irradiated lesion has clearly progressed OR a new lesion has developed in the irradiated field
  • Failed 1, and only 1, line of prior chemotherapy for advanced/metastatic disease

    • Disease progression during chemotherapy OR within 6 months after completion of treatment
  • No symptomatic brain metastases meeting any of the following criteria:

    • Unstable
    • Inadequately controlled with fixed-dose oral steroids
    • Potentially life-threatening
    • Required radiotherapy with the past 28 days

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-2

Life expectancy

  • Not specified

Hematopoietic

  • Neutrophil count > 1,500/mm^3
  • Platelet count > 100,000/mm^3

Hepatic

  • AST and ALT < 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases are present)
  • Bilirubin < 1.5 times ULN
  • No hepatitis
  • No cirrhosis

Renal

  • Creatinine < 1.5 times ULN

Other

  • Not pregnant
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after study participation
  • HIV negative
  • No preexisting neuropathy ≥ grade 2
  • No active or uncontrolled infection
  • No other serious illness or medical condition
  • No chronic alcohol abuse
  • No known hypersensitivity to systemic liposomal formulations or compounds chemically related to OSI-7904L or oxaliplatin
  • No prior psychiatric or neurologic condition that would preclude study compliance or giving informed consent

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • At least 21 days since prior immunotherapy
  • At least 21 days since prior monoclonal antibody therapy

Chemotherapy

  • See Disease Characteristics
  • At least 21 days since prior chemotherapy and recovered*
  • No prior oxaliplatin NOTE: *Alopecia allowed

Endocrine therapy

  • See Disease Characteristics
  • At least 21 days since prior hormonal therapy

Radiotherapy

  • See Disease Characteristics
  • At least 21 days since prior radiotherapy and recovered
  • No prior radiotherapy to more than 25% of bone marrow reserve

Surgery

  • Recovered from prior surgery

Other

  • At least 21 days since prior tyrosine kinase inhibitor therapy
  • More than 21 days since prior investigational agents
  • No other concurrent anticancer therapy
  • No other concurrent investigational agents
  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: NCT00081237

Locations
Germany
Medizinische Hochschule Hannover
Hannover, Germany, D-30625
United Kingdom
Christie Hospital N.H.S. Trust
Manchester, England, United Kingdom, M20 4BX
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Investigators
Study Chair: Patrick Schoffski, MD, MPH Hannover Medical School
  More Information

Additional Information:
Publications:
Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT00081237     History of Changes
Other Study ID Numbers: EORTC-16033, EORTC-16033, OSI-EORTC-16033
Study First Received: April 7, 2004
Last Updated: June 11, 2013
Health Authority: United States: Federal Government

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
recurrent colon cancer
stage III colon cancer
stage IV colon cancer
recurrent rectal cancer
stage III rectal cancer
stage IV rectal cancer

Additional relevant MeSH terms:
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Colonic Diseases
Oxaliplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 18, 2014