Monoclonal Antibody Therapy in Treating Patients With Advanced Colorectal Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00027729
First received: December 7, 2001
Last updated: June 4, 2013
Last verified: June 2013
  Purpose

RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.

PURPOSE: Phase I/II trial to study the effectiveness of monoclonal antibody therapy in treating patients who have advanced colorectal cancer that has not responded to irinotecan.


Condition Intervention Phase
Colorectal Cancer
Biological: etaracizumab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: Phase I/II Study of MEDI-522, A Humanized Monoclonal Antibody Directed Against the Human Alpha V Beta 3 Integrin, in Patients With Irinotecan-Refractory Advanced Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Study Start Date: June 2001
Study Completion Date: November 2004
Primary Completion Date: November 2004 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • Determine the recommended phase II dose of monoclonal antibody anti-anb3 integrin in patients with irinotecan-refractory advanced colorectal cancer.
  • Determine the safety and tolerance of this drug in these patients.
  • Determine any antitumor activity of this drug in these patients.
  • Determine the objective response rate, response duration, and time to progression in patients treated with this drug.
  • Determine the pharmacokinetics of this drug in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive monoclonal antibody anti-anb3 integrin IV over 30 minutes once weekly on weeks 1-52 in the absence of disease progression or unacceptable toxicity. Patients with responding disease may continue therapy.

Cohort of 4-6 patients receive escalating doses of monoclonal antibody anti-anb3 integrin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 4 or 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are treated at that dose in the phase II portion of the study.

Patients are followed every 3 months for 2 years.

PROJECTED ACCRUAL: A total of 4-24 patients will be accrued for phase I of this study and a total of 40 patients will be accrued for phase II of 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 advanced colorectal cancer
  • Disease progression while receiving an irinotecan-containing regimen for metastatic colorectal cancer OR
  • Disease recurrence within 6 months after completing an irinotecan-containing regimen in the adjuvant setting
  • At least 1 measurable lesion (for phase II only)

    • At least 20 mm by x-ray, CT scan, MRI, or photograph
    • Recurrent disease after surgery or radiotherapy is considered measurable if it has been at least 4 weeks since treatment and measurable disease is outside the port of prior radiotherapy or there is evidence of disease progression within the port of prior radiotherapy
    • The following are not considered measurable:

      • Pleural effusion
      • Ascites
      • Osteoblastic lesion or evidence of disease on bone scan alone
      • Progressive irradiated lesions alone
      • Bone marrow involvement
      • Brain metastases
      • Malignant hepatomegaly by physical exam alone
      • Chemical markers (e.g., carcinoembryonic antigen)
  • No known brain metastases or primary brain tumors
  • No symptomatic pleural effusion or ascites requiring paracentesis
  • No clinical evidence of bowel obstruction

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • ECOG 0-1

Life expectancy:

  • Not specified

Hematopoietic:

  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • Hemoglobin greater than 10.0 g/dL

Hepatic:

  • Bilirubin no greater than 2.0 mg/dL
  • AST/ALT no greater than 5 times upper limit of normal (ULN)
  • PT/PTT less than ULN OR
  • INR less than 1.12
  • No hepatitis virus infection

Renal:

  • Creatinine no greater than 1.5 mg/dL OR
  • Creatinine clearance greater than 50 mL/min

Cardiovascular:

  • No prior myocardial infarction
  • No angina
  • No uncontrolled hypertension (systolic blood pressure greater than 150 mm Hg)
  • No prior cerebrovascular accident or transient ischemic attack

Pulmonary:

  • No respiratory insufficiency requiring oxygen treatment
  • No lymphangitic involvement of lungs

Other:

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception for 30 days before, during, and for 30 days after study
  • Thyroxine and thyroid-stimulating hormone normal
  • No hematemesis, melena, hematochezia, or gross hematuria
  • No prior significant adverse reaction to a humanized monoclonal antibody
  • No known HIV infection
  • No active infection requiring systemic anti-infective therapy
  • No other medical or psychological condition or behavior, including substance dependence or abuse, that would preclude study
  • No other malignancy within the past 5 years except basal cell skin cancer or completely excised carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Prior immunotherapy with approved agents allowed
  • No prior monoclonal antibody anti-anb3 integrin or its precursor (MEDI-523)
  • No other concurrent immunotherapy

Chemotherapy:

  • See Disease Characteristics
  • At least 4 weeks since prior chemotherapy
  • No concurrent palliative chemotherapy

Endocrine therapy:

  • No concurrent hormonal therapy

Radiotherapy:

  • See Disease Characteristics
  • At least 4 weeks since prior radiotherapy

Surgery:

  • See Disease Characteristics
  • At least 4 weeks since prior surgery and surgical wounds must have healed

Other:

  • Recovered from all prior therapy
  • At least 4 weeks since prior 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: NCT00027729

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Study Chair: Leonard B. Saltz, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00027729     History of Changes
Other Study ID Numbers: 01-078, CDR0000069061, MEDIMMUNE-MI-CP068, NCI-G01-2032
Study First Received: December 7, 2001
Last Updated: June 4, 2013
Health Authority: United States: Federal Government

Keywords provided by Memorial Sloan-Kettering Cancer Center:
recurrent colon cancer
recurrent rectal cancer

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
Antibodies, Monoclonal
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 21, 2014