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

NCT ID: NCT00004087

Last Updated: 2011-06-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1997-03-31

Brief Summary

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.

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.

Conditions

Colorectal Cancer; Pancreatic Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

filgrastim

as prescribed by physician

Intervention Type: BIOLOGICAL

autologous bone marrow transplantation

1-2 weeks before treatment

Intervention Type: PROCEDURE

peripheral blood stem cell transplantation

1-2 weeks before treatment

Intervention Type: PROCEDURE

indium In 111 monoclonal antibody MN-14

intravenous infusion over 30 min; single dose

Intervention Type: RADIATION

yttrium Y 90 monoclonal antibody MN-14

intravenous infusion over 30 min; single dose

Intervention Type: RADIATION

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Garden State Cancer Center at the Center for Molecular Medicine and Immunology

OTHER

Sponsor Role: lead

Responsible Party

GSCC

Principal Investigators

Jack D. Burton, MD

Role: STUDY_CHAIR

Garden State Cancer Center at the Center for Molecular Medicine and Immunology

Locations

Garden State Cancer Center

Belleville, New Jersey, United States

St. Joseph's Hospital and Medical Center

Paterson, New Jersey, United States

University of Pennsylvania Cancer Center

Philadelphia, Pennsylvania, United States

Countries

United States

Other Identifiers

P01CA054425

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CMMI-C-033-98

Identifier Type: -

Identifier Source: secondary_id

NCI-H99-0042

Identifier Type: -

Identifier Source: secondary_id

NCI-V99-1571

Identifier Type: -

Identifier Source: secondary_id

CDR0000067300

Identifier Type: -

Identifier Source: org_study_id