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

Recurrent Rectal Cancer Clinical Trial

Official title:

Phase I Trial of Radioimmunotherapy (Y-90 M5A) in Combination With FOLFIRI and Bevacizumab Chemotherapy for Metastatic Colorectal Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01205022
• Other study ID #: 10038
• Secondary ID: NCI-2010-01962
• Status: Completed
• Phase: Phase 1
• First received: September 16, 2010
• Last updated: June 3, 2015
• Start date: April 2011
• Est. completion date: January 2014

Study information

• Verified date: June 2015
• Source: City of Hope Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3
• Est. completion date: January 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Rectal Neoplasms
• Recurrent Colon Cancer
• Recurrent Rectal Cancer
• Stage IV Colon Cancer
• Stage IV Rectal Cancer

Intervention

Drug:
• irinotecan hydrochloride
Given IV
• leucovorin calcium
Given IV
• fluorouracil
Given IV

Biological:
• bevacizumab
Given IV

Radiation:
• yttrium Y 90 DOTA anti-CEA monoclonal antibody M5A
Given IV

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	City of Hope Medical Center	Duarte	California

Sponsors (2)

Lead Sponsor	Collaborator
City of Hope Medical Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose of yttrium-90 (90Y) M5A anti-CEA antibody when given in combination with FOLFIRI chemotherapy and bevacizumab		1 year post treatment	Yes
Secondary	Progression-free survival		2 years post treatment	No
Secondary	Overall survival		2 years post treatment	No
Secondary	Response rates		2 years post treatment	No
Secondary	Biodistribution, clearance, and metabolism of Y-90 and In-111-M5A		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	No
Secondary	Estimation of radiation doses to whole body, normal organs, and tumor through serial nuclear imaging		At 1-3 hours post start of antibody infusion, 1 day, 2 days, 3-5 days, and 6-7 days post antibody infusion	No