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

September 16, 2010
January 29, 2014
April 2011
January 2014   (final data collection date for primary outcome measure)
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 ]
Maximum tolerated dose of a combination of FOLFIRI chemotherapy and yttrium-90 (90Y) M5A anti-CEA antibody [ Time Frame: 1 year post treatment ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01205022 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
Radiolabeled Monoclonal Antibody Therapy, Combination Chemotherapy, and Bevacizumab in Treating Patients With Metastatic Colorectal Cancer
Phase I Trial of Radioimmunotherapy (Y-90 M5A) in Combination With FOLFIRI and Bevacizumab Chemotherapy for Metastatic Colorectal Carcinoma

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.

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.

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Recurrent Colon Cancer
  • Recurrent Rectal Cancer
  • Stage IV Colon Cancer
  • Stage IV Rectal Cancer
  • 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
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.
Interventions:
  • Drug: irinotecan hydrochloride
  • Drug: leucovorin calcium
  • Drug: fluorouracil
  • Biological: bevacizumab
  • Radiation: yttrium Y 90 DOTA anti-CEA monoclonal antibody M5A
  • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
3
Not Provided
January 2014   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01205022
10038, NCI-2010-01962
Yes
City of Hope Medical Center
City of Hope Medical Center
National Cancer Institute (NCI)
Principal Investigator: Jeffrey Wong, MD City of Hope Medical Center
City of Hope Medical Center
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP