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

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

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.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer; Pancreatic Cancer
• Intervention / Treatment: Biological: filgrastim; Radiation: indium In 111 monoclonal antibody MN-14; Radiation: yttrium Y 90 monoclonal antibody MN-14; Procedure: autologous bone marrow transplantation; Procedure: peripheral blood stem cell transplantation

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.

• Study Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Belleville, New Jersey, United States, 07103
      • Garden State Cancer Center
    • Paterson, New Jersey, United States, 07503
      • St. Joseph's Hospital and Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
maximum tolerated dose	12 weeks

Collaborators and Investigators

• Sponsor: Garden State Cancer Center at the Center for Molecular Medicine and Immunology
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: March 1, 1997
• Primary Completion (ACTUAL): May 1, 2001

Study Registration Dates

• First Submitted: December 10, 1999
• First Submitted That Met QC Criteria: April 15, 2004
• First Posted (ESTIMATE): April 16, 2004

Study Record Updates

• Last Update Posted (ESTIMATE): June 22, 2011
• Last Update Submitted That Met QC Criteria: June 21, 2011
• Last Verified: June 1, 2011

More Information

Terms related to this study

• Keywords: stage IV rectal cancer; stage IV colon cancer; recurrent colon cancer; recurrent rectal cancer; recurrent pancreatic cancer; stage IV pancreatic cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Endocrine Gland Neoplasms; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Pancreatic Diseases; Colorectal Neoplasms; Pancreatic Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Antineoplastic Agents, Immunological
• Other Study ID Numbers: CDR0000067300; P01CA054425 (NIH); CMMI-C-033-98; NCI-H99-0042; NCI-V99-1571