Radiolabeled Monoclonal Antibody Therapy, Combination Chemotherapy, and Bevacizumab in Treating Patients With Metastatic Colorectal Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT01205022
First received: September 16, 2010
Last updated: January 29, 2014
Last verified: January 2014
  Purpose

RATIONALE: Radiolabeled monoclonal antibodies can find tumor cells and either kill them or carry tumor-killing substances to them without harming normal cells. Giving radioactive substances together with antibodies may be effective treatment for some advanced cancers. Drugs used in chemotherapy, such as irinotecan hydrochloride, fluorouracil, and leucovorin calcium (FOLFIRI), work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving radiolabeled monoclonal antibodies together with combination chemotherapy and bevacizumab may be an effective treatment for colorectal cancer.

PURPOSE: This phase I trial is studying the side effects, best way to give, and best dose of yttrium Y 90 DOTA anti-CEA (Carcinoembryonic antigen) monoclonal antibody M5A when given together with combination chemotherapy and bevacizumab in treating patients with metastatic colorectal cancer.


Condition Intervention Phase
Recurrent Colon Cancer
Recurrent Rectal Cancer
Stage IV Colon Cancer
Stage IV Rectal Cancer
Drug: irinotecan hydrochloride
Drug: leucovorin calcium
Drug: fluorouracil
Biological: bevacizumab
Radiation: yttrium Y 90 DOTA anti-CEA monoclonal antibody M5A
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Trial of Radioimmunotherapy (Y-90 M5A) in Combination With FOLFIRI and Bevacizumab Chemotherapy for Metastatic Colorectal Carcinoma

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • Maximum tolerated dose of yttrium-90 (90Y) M5A anti-CEA antibody when given in combination with FOLFIRI chemotherapy and bevacizumab [ Time Frame: 1 year post treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: 2 years post treatment ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 2 years post treatment ] [ Designated as safety issue: No ]
  • Response rates [ Time Frame: 2 years post treatment ] [ Designated as safety issue: No ]
  • Biodistribution, clearance, and metabolism of Y-90 and In-111-M5A [ Time Frame: At baseline, 1 hour, and 4 hours post start of infusion and at scan times at 1 day, 2 days, 3-5 days, and 6-7 days post antibody infusion ] [ Designated as safety issue: No ]
  • Estimation of radiation doses to whole body, normal organs, and tumor through serial nuclear imaging [ Time Frame: At 1-3 hours post start of antibody infusion, 1 day, 2 days, 3-5 days, and 6-7 days post antibody infusion ] [ Designated as safety issue: No ]

Enrollment: 3
Study Start Date: April 2011
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive irinotecan hydrochloride IV over 90 minutes, leucovorin calcium IV over 2 hours, fluorouracil IV continuously over 46-48 hours, and bevacizumab IV over 30-90 minutes once every 2 weeks. Patients also receive yttrium Y 90 DOTA anti-CEA monoclonal antibody M5A IV over 25 minutes once in weeks 3 and 9.Treatment continues in the absence of disease progression or unacceptable toxicity.
Drug: irinotecan hydrochloride
Given IV
Other Names:
  • Campto
  • Camptosar
  • camptothecin-11
  • CPT-11
  • irinotecan
  • U-101440E
Drug: leucovorin calcium
Given IV
Other Names:
  • calcium folinate
  • CF
  • CFR
  • citrovorum factor
  • LV
  • Wellcovorin
Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
  • Adrucil
  • Efudex
  • FU
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • anti-VEGF rhuMAb
  • Avastin
  • rhuMAb VEGF
Radiation: yttrium Y 90 DOTA anti-CEA monoclonal antibody M5A
Given IV
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose of a combination of FOLFIRI chemotherapy, and intravenous yttrium-90 (90Y) M5A anti-CEA antibody.

SECONDARY OBJECTIVES:I. To study the progression free survival and response rate of this combined treatment in patients with stage IV colorectal cancer.II. To evaluate the biodistribution, clearance and metabolism of 90Y and 111In (indium-111) M5A administered intravenously.

OUTLINE: This is a dose-escalation study of yttrium Y 90 DOTA anti-CEA monoclonal antibody M5A. Patients receive irinotecan hydrochloride IV over 90 minutes, leucovorin calcium IV over 2 hours, fluorouracil IV continuously over 46-48 hours, and bevacizumab IV over 30-90 minutes once every 2 weeks. Patients also receive yttrium Y 90 DOTA anti-CEA monoclonal antibody M5A IV over 25 minutes once in weeks 3 and 9. Treatment continues in the absence of disease progression or unacceptable toxicity.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have a Karnofsky performance status of > 60%
  • Patients must have histological confirmation of colorectal carcinoma with stage IV disease or with unresectable disease
  • Patients must have colorectal tumors that produce CEA as documented by either immunohistochemistry or by an elevated serum CEA
  • Prior radiotherapy, immunotherapy, or chemotherapy must have been completed no less than 28 days prior to patient entry on this study and patients must have recovered from all acute expected side effects of the prior therapy. For patients who have undergone port placement, study treatment initiation must be at least 7 days post port placement
  • Adequate bone marrow function as evidenced by hemoglobin > 10 g/dL, WBC > 4000/ul, an absolute granulocyte count of > 1,500/mm^3, and platelets > 150,000/ul; patients may be transfused to reach a hemoglobin > 10 g/dL
  • In the dose-escalation phase, patients may have had a history of a prior malignancy; for the dose-expansion cohort, patients may have history of prior malignancy for which they have been disease free for five years with the exception of basal or squamous cell skin cancers or carcinoma in situ of the cervix
  • Patients must have a total bilirubin < 1.5 mg/dL and a serum creatinine of < 2.0 mg/dL
  • If a patient has previously received antibody, then serum anti-antibody testing must be negative
  • Serum HIV testing and hepatitis B surface antigen and C antibody testing must be negative
  • Women of childbearing potential must have a negative serum pregnancy test prior to entry and while on study must be practicing an effective form of contraception
  • Patients must have measurable disease as defined by the modified RECIST criteria

Exclusion Criteria:

  • Patients who have received radiation therapy to greater than 50% of their bone marrow
  • Patients with any nonmalignant intercurrent illness (example cardiovascular, pulmonary, or central nervous system disease) that is either poorly controlled with currently available treatment or that is of such severity that the investigators deem it unwise to enter the patient on protocol shall be ineligible
  • Patients with > 2+ protein by dipstick should undergo a 24 hour urine collection; patients with > 1gram proteinuria/ 24 hours are not eligible
  • Patients may have received neoadjuvant and/or adjuvant chemotherapy and/or radiotherapy and present to the study in relapse; otherwise, no prior therapy is allowed
  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: NCT01205022

Locations
United States, California
City of Hope Medical Center
Duarte, California, United States, 91010
Sponsors and Collaborators
City of Hope Medical Center
Investigators
Principal Investigator: Jeffrey Wong, MD City of Hope Medical Center
  More Information

No publications provided

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT01205022     History of Changes
Other Study ID Numbers: 10038, NCI-2010-01962
Study First Received: September 16, 2010
Last Updated: January 29, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Colonic Neoplasms
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Fluorouracil
Calcium, Dietary
Camptothecin
Irinotecan
Bevacizumab
Leucovorin
Levoleucovorin
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 22, 2014