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

NCT01205022 | Completed Phase 1 DMC

• 2 other identifiers: 10038NCI-2010-01962
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage IV Colon Cancer; Stage IV Rectal Cancer

Outcome Measures

Primary Outcomes (1)

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

  1 year post treatment

Secondary Outcomes (5)

• Progression-free survival

  2 years post treatment

• Overall survival

  2 years post treatment

• Response rates

  2 years post treatment

• 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

• 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

Study Arms (1)

Arm I

EXPERIMENTAL

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; Drug: leucovorin calcium; Drug: fluorouracil; Biological: bevacizumab; Radiation: yttrium Y 90 DOTA anti-CEA monoclonal antibody M5A; Other: laboratory biomarker analysis

Interventions

irinotecan hydrochloride DRUG

Given IV

Also known as: Campto, Camptosar, camptothecin-11, CPT-11, irinotecan, U-101440E

Arm I

leucovorin calcium DRUG

Given IV

Also known as: calcium folinate, CF, CFR, citrovorum factor, LV, Wellcovorin

Arm I

fluorouracil DRUG

Given IV

Also known as: 5-fluorouracil, 5-Fluracil, 5-FU, Adrucil, Efudex, FU

Arm I

bevacizumab BIOLOGICAL

Given IV

Also known as: anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, anti-VEGF rhuMAb, Avastin, rhuMAb VEGF

Arm I

yttrium Y 90 DOTA anti-CEA monoclonal antibody M5A RADIATION

Given IV

Arm I

laboratory biomarker analysis OTHER

Correlative studies

Arm I

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Colonic Neoplasms; Rectal Neoplasms

Interventions

Irinotecan; Leucovorin; Fluorouracil; Bevacizumab

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Jeffrey Wong, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2010
• First Posted: September 20, 2010
• Study Start: April 1, 2011
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: June 8, 2015

Record last verified: 2015-06

Locations

US (1)