Combination Chemotherapy and Bevacizumab Before Surgery and Radiolabeled Monoclonal Antibody Therapy in Treating Liver Metastases in Patients With Metastatic Colorectal Cancer

NCT01320683 | Terminated Phase 2 Results DMC

• 3 other identifiers: 09053NCI-2011-00369P01CA043904
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well giving combination chemotherapy and bevacizumab before surgery and radiolabeled monoclonal antibody therapy works in treating liver metastases in patients with metastatic colorectal cancer. Drugs used in chemotherapy, such as leucovorin calcium, fluorouracil, and oxaliplatin (FOLFOX), 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 to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Radiolabeled monoclonal antibodies, such as yttrium Y 90 DOTA anti-CEA monoclonal antibody M5A, can find tumor cells and carry tumor-killing substances to them without harming normal cells. Giving chemotherapy and monoclonal antibody before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving radiolabeled monoclonal antibody therapy after surgery may kill any tumor cells that remain after surgery

Conditions

Liver Metastases; Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival

  Estimated using the product-limit method of Kaplan-Meier, and 95% confidence limits calculated for these estimates. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

  Up to 24 months

Secondary Outcomes (1)

• Overall Survival

  Up to 5 years

Study Arms (1)

Treatment (combination chemotherapy and radioimmunotherapy)

EXPERIMENTAL

FOLFOX\* + BEVACIZUMAB CHEMOTHERAPY: Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, fluorouracil IV continuously over 46-48 hours, and bevacizumab IV over 30-90 minutes. Treatment repeats for up to 12 courses in the absence of disease progression or unacceptable toxicity. RIT: Within 4-12 weeks after completion of post-hepatic resection therapy chemotherapy, patients receive yttrium Y 90 DOTA anti-CEA monoclonal antibody M5A IV over 25 minutes. Treatment repeats every 6-10 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. NOTE:\*Patients previously failing oxaliplatin regimen receive FOLIFIRI chemotherapy comprising irinotecan hydrochloride IV over 90 minutes, leucovorin calcium over 2 hours, fluorouracil IV continuously over 46-48 hours, and bevacizumab IV over 30-90 minutes. Treatment repeats for up to 6 courses in the absence of disease progression or unacceptable toxicity.

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

Interventions

oxaliplatin DRUG

Given IV

Also known as: 1-OHP, Dacotin, Dacplat, Eloxatin, L-OHP

Treatment (combination chemotherapy and radioimmunotherapy)

leucovorin calcium DRUG

Given IV

Also known as: CF, CFR, LV

Treatment (combination chemotherapy and radioimmunotherapy)

fluorouracil DRUG

Given IV

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

Treatment (combination chemotherapy and radioimmunotherapy)

bevacizumab BIOLOGICAL

Given IV

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

Treatment (combination chemotherapy and radioimmunotherapy)

yttrium Y 90 DOTA anti-CEA monoclonal antibody M5A RADIATION

Given IV

Treatment (combination chemotherapy and radioimmunotherapy)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (combination chemotherapy and radioimmunotherapy)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (combination chemotherapy and radioimmunotherapy)

irinotecan hydrochloride DRUG

Given IV

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

Treatment (combination chemotherapy and radioimmunotherapy)

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
• Patients must have colorectal tumors that produce carcinoembryonic antigen (CEA) as documented by either immunohistochemistry or by an elevated serum CEA
• Patients will be enrolled on this trial after resection of hepatic metastases combined with FOLFIRI or FOLFOX \[+/- Bevacizumab\], or XELOX; patients may have received a maximum of 12 cycles of FOLFIRI or FOLFOX \[+/- Bevacizumab\], or XELOX, which includes chemotherapy prior to and post hepatic resection
• Prior radiotherapy, immunotherapy, or chemotherapy must have been completed between 4-12 weeks prior to patient entry on this study and patients must have recovered from all expected acute side effects of the prior therapy
• Hemoglobin \>= 10 gm %; patients may be transfused to reach a hemoglobin \>= 10 gm %
• White blood cell (WBC) \>= 4000/uL
• Absolute neutrophil count (ANC) \>= 1,500/mm\^3
• Platelets \>= 150,000/ul
• Patients may have history of prior malignancy for which the patient has been disease-free for five years; basal or squamous cell skin cancers or carcinoma in situ of the cervix are allowed regardless of diagnosis date
• Patients must have no prior history of radiation therapy to the liver (includes 90Y microsphere therapy)
• Patients must have a total bilirubin =\< 1.5 mg/dL
• Serum creatinine of =\< 1.5 x upper limit of normal (ULN)
• Patients must have had \< 40% liver resected at the close of completion of the hepatic resection; this will be verified retrospectively
• Serum human immunodeficiency virus (HIV) testing and hepatitis B surface antigen and hepatitis C antibody testing must be negative

You may not qualify if:

• Patients that 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) which is either poorly controlled with currently available treatment or which is of such severity that the investigators deem it unwise to enter the patient on protocol shall be ineligible
• Chronic active hepatitis, cirrhosis, or chemotherapy steatohepatitis

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

Oxaliplatin; Leucovorin; Fluorouracil; Bevacizumab; Irinotecan

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)

Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; 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; Camptothecin; Alkaloids

Limitations and Caveats

Early termination due to slow accrual. Unable to perform planned analysis due to the small number of subjects.

Results Point of Contact

• Title: Paul Frankel, Ph.D.
• Organization: City of Hope

pfrankel@coh.org

626-256-4673

Study Officials

• Jeffrey Wong

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2011
• First Posted: March 22, 2011
• Study Start: March 1, 2011
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: July 19, 2016
• Results First Posted: June 20, 2016

Record last verified: 2016-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)