Radiolabeled Monoclonal Antibody Therapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Metastatic or Recurrent Colorectal Cancer or Pancreatic Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Garden State Cancer Center at the Center for Molecular Medicine and Immunology
ClinicalTrials.gov Identifier:
NCT00004087
First received: December 10, 1999
Last updated: June 21, 2011
Last verified: June 2011
  Purpose

RATIONALE: Radiolabeled monoclonal antibodies can locate tumor cells and deliver tumor-killing substances to them without harming normal cells. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by monoclonal antibody therapy used to kill tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of radiolabeled monoclonal antibody plus peripheral stem cell transplantation in treating patients who have metastatic or recurrent colorectal cancer or pancreatic cancer that has not responded to previous treatment.


Condition Intervention Phase
Colorectal Cancer
Pancreatic Cancer
Biological: filgrastim
Procedure: autologous bone marrow transplantation
Procedure: peripheral blood stem cell transplantation
Radiation: indium In 111 monoclonal antibody MN-14
Radiation: yttrium Y 90 monoclonal antibody MN-14
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Radioimmunotherapy With High-Dose 90Y-Labeled Humanized MN-14 in Advanced Metastatic Colorectal Cancer and Pancreatic Cancers Using Autologous Peripheral Blood Stem Cell Rescue (PBSCR) to Control Myelotoxicity

Resource links provided by NLM:


Further study details as provided by Garden State Cancer Center at the Center for Molecular Medicine and Immunology:

Primary Outcome Measures:
  • maximum tolerated dose [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 15
Study Start Date: March 1997
Primary Completion Date: May 2001 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: filgrastim
    as prescribed by physician
    Procedure: autologous bone marrow transplantation
    1-2 weeks before treatment
    Procedure: peripheral blood stem cell transplantation
    1-2 weeks before treatment
    Radiation: indium In 111 monoclonal antibody MN-14
    intravenous infusion over 30 min; single dose
    Radiation: yttrium Y 90 monoclonal antibody MN-14
    intravenous infusion over 30 min; single dose
Detailed Description:

OBJECTIVES: I. Determine the maximum tolerated dose and secondary organ toxicity of high dose yttrium Y 90 monoclonal antibody MN-14 (90Y-hMN-14) plus autologous peripheral blood stem cell rescue in patients with metastatic or recurrent colorectal or pancreatic cancer. II. Compare the tumor to organ dose ratio between 90Y-hMN-14 and iodine 131 monoclonal antibody MN-14 (131I-MN-14) in these patients. III. Determine the antitumor effects with myeloablative doses of 90Y-hMN-14. IV. Evaluate the immunogenicity of 90Y-hMN-14 in these patients.

OUTLINE: This is a dose escalation of yttrium Y 90 monoclonal antibody MN-14 (90Y-hMN-14), multicenter study. Patients are stratified by prior radiotherapy (yes vs no). Patients receive filgrastim (G-CSF) subcutaneously on days -18 to -14 and peripheral blood stem cell (PBSC) collection on days -15 to -13. If an adequate number of CD34+ cells are not harvested, bone marrow is also collected. Patients receive pretherapy imaging with indium In 111 monoclonal antibody MN-14 (IN111-MN-14) IV on days -7 to 0. Patients receive 90Y-hMN-14 for up to 40 minutes on day 0. PBSC are reinfused on days 7 to 14. Patients receive G-CSF SQ until blood counts recover. Cohorts of 3-6 patients receive escalating doses of 90Y-hMN-14 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 3 or 2 of 6 patients experience dose limiting toxicity. Patients are followed at 1-4, 6, 8, 12, and 24 weeks, and then every 6 months thereafter for up to 5 years.

PROJECTED ACCRUAL: A total of 24-30 patients will be accrued for this study within 2 years.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS: Histologically or cytologically proven metastatic or recurrent colorectal or pancreatic cancer for which no curative surgery exists Failed at least 1 regimen of standard fluorouracil based chemotherapy for metastatic colorectal cancer or gemcitabine for pancreatic cancer Autologous peripheral blood stem cells (PBSC) or bone marrow available Diffuse bone marrow involvement allowed if: Autologous bone marrow or PBSC with no greater than 5% tumor involvement available Tumor site at least 2.0 cm in diameter confirmed by pretherapy indium In 111 monoclonal antibody MN-14 imaging and CT scan

PATIENT CHARACTERISTICS: Age: 18 to 80 Performance status: Karnofsky 70-100% ECOG 0-2 Life expectancy: At least 3 months Hematopoietic: WBC at least 3,000/mm3 Granulocyte count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 2 mg/dL SGOT no greater than 2.0 times upper limit of normal (ULN) Renal: Creatinine no greater than ULN Other: No severe anorexia, nausea, or vomiting No concurrent significant medical complications that would preclude compliance Not pregnant Fertile patients must use effective contraception during and for 3 months after study No allergy to 90Y-hMN-14

PRIOR CONCURRENT THERAPY: Biologic therapy: Prior murine monoclonal antibody allowed Chemotherapy: No prior irinotecan At least 4 weeks since prior chemotherapy and recovered (8 weeks since nitrosourea, mitomycin or 90Y-hMN-14) Endocrine therapy: Not specified Radiotherapy: At least 4 weeks since prior radiotherapy to index lesion and recovered No prior radiotherapy to greater than 25% of red marrow (pelvic field radiation as adjuvant therapy for rectal cancer allowed) No prior radiotherapy to maximum tolerated dose to any critical organ (e.g., lung, liver, or kidney) Surgery: At least 4 weeks since major surgery

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00004087

Locations
United States, New Jersey
Garden State Cancer Center
Belleville, New Jersey, United States, 07103
St. Joseph's Hospital and Medical Center
Paterson, New Jersey, United States, 07503
United States, Pennsylvania
University of Pennsylvania Cancer Center
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Garden State Cancer Center at the Center for Molecular Medicine and Immunology
Investigators
Study Chair: Jack D. Burton, MD Garden State Cancer Center at the Center for Molecular Medicine and Immunology
  More Information

Additional Information:
No publications provided

Responsible Party: Robert M Sharkey, GSCC
ClinicalTrials.gov Identifier: NCT00004087     History of Changes
Other Study ID Numbers: CDR0000067300, P01CA054425, CMMI-C-033-98, NCI-H99-0042, NCI-V99-1571
Study First Received: December 10, 1999
Last Updated: June 21, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Garden State Cancer Center at the Center for Molecular Medicine and Immunology:
stage IV colon cancer
stage IV pancreatic cancer
recurrent pancreatic cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Pancreatic Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Endocrine Gland Neoplasms
Pancreatic Diseases
Endocrine System Diseases
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Lenograstim
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Adjuvants, Immunologic

ClinicalTrials.gov processed this record on August 21, 2014