Clinical trial NCT00004087: Radiolabeled Monoclonal Antibody Therapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Metastatic or Recurrent Colorectal Cancer or Pancreatic Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Colorectal Cancer
Pancreatic Cancer
Keywords: stage IV colon cancer
stage IV pancreatic cancer
recurrent pancreatic cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer
Lead sponsor: Garden State Cancer Center at the Center for Molecular Medicine and Immunology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-04-16
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: maximum tolerated dose
timeFrame: 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Belleville
country: United States
facility: Garden State Cancer Center
state: New Jersey
city: Paterson
country: United States
facility: St. Joseph's Hospital and Medical Center
state: New Jersey
city: Philadelphia
country: United States
facility: University of Pennsylvania Cancer Center
state: Pennsylvania
Study officials:
affiliation: Garden State Cancer Center at the Center for Molecular Medicine and Immunology
name: Jack D. Burton, MD
role: STUDY_CHAIR
References: