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

Primary Purpose

Recurrent Colon Cancer, Recurrent Rectal Cancer, Stage IV Colon Cancer

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

irinotecan hydrochloride

leucovorin calcium

fluorouracil

bevacizumab

yttrium Y 90 DOTA anti-CEA monoclonal antibody M5A

laboratory biomarker analysis

About this trial

This is an interventional treatment trial for Recurrent Colon Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

City of Hope Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm I

Arm Description

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.

Outcomes

Primary Outcome Measures

Maximum tolerated dose of yttrium-90 (90Y) M5A anti-CEA antibody when given in combination with FOLFIRI chemotherapy and bevacizumab

Secondary Outcome Measures

Progression-free survival

Overall survival

Response rates

Biodistribution, clearance, and metabolism of Y-90 and In-111-M5A

Estimation of radiation doses to whole body, normal organs, and tumor through serial nuclear imaging

Full Information

NCT ID

NCT01205022

First Posted

September 16, 2010

Last Updated

June 3, 2015

Sponsor

City of Hope Medical Center

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT01205022

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2015

Overall Recruitment Status

Completed

Study Start Date

April 2011 (undefined)

Primary Completion Date

January 2014 (Actual)

Study Completion Date

January 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

City of Hope Medical Center

Collaborators

National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Recurrent Colon Cancer, Recurrent Rectal Cancer, Stage IV Colon Cancer, Stage IV Rectal Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

3 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm I

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

irinotecan hydrochloride

Other Intervention Name(s)

Campto, Camptosar, camptothecin-11, CPT-11, irinotecan, U-101440E

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

leucovorin calcium

Other Intervention Name(s)

calcium folinate, CF, CFR, citrovorum factor, LV, Wellcovorin

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

fluorouracil

Other Intervention Name(s)

5-fluorouracil, 5-Fluracil, 5-FU, Adrucil, Efudex, FU

Intervention Description

Given IV

Intervention Type

Biological

Intervention Name(s)

bevacizumab

Other Intervention Name(s)

anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, anti-VEGF rhuMAb, Avastin, rhuMAb VEGF

Intervention Description

Given IV

Intervention Type

Radiation

Intervention Name(s)

yttrium Y 90 DOTA anti-CEA monoclonal antibody M5A

Intervention Description

Given IV

Intervention Type

Other

Intervention Name(s)

laboratory biomarker analysis

Intervention Description

Correlative studies

Primary Outcome Measure Information:

Title

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

Secondary Outcome Measure Information:

Title

Progression-free survival

Time Frame

2 years post treatment

Title

Overall survival

Time Frame

2 years post treatment

Title

Response rates

Time Frame

2 years post treatment

Title

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

Title

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jeffrey Wong, MD

Organizational Affiliation

City of Hope Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

City of Hope Medical Center

City

Duarte

State/Province

California

ZIP/Postal Code

91010

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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