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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT01320683
First received: March 18, 2011
Last updated: July 17, 2014
Last verified: July 2014
  Purpose

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


Condition Intervention Phase
Liver Metastases
Recurrent Colon Cancer
Recurrent Rectal Cancer
Stage IVA Colon Cancer
Stage IVA Rectal Cancer
Stage IVB Colon Cancer
Stage IVB Rectal Cancer
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
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Radioimmunotherapy (Y-90 M5A) Following Hepatic Resection and FOLFIRI or FOLFOX Chemotherapy [+/-BEVACIZUMAB], or Xelox for Metastatic Colorectal Carcinoma to the Liver

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: 1 year after completion of study treatment ] [ Designated as safety issue: No ]
    Estimated using the product-limit method of Kaplan-Meier, and 95% confidence limits calculated for these estimates.


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: 6 years after completion of treatment ] [ Designated as safety issue: No ]
  • Biodistribution [ Time Frame: 6 months after completion of treatment ] [ Designated as safety issue: No ]
  • Clearance and metabolism of yttrium Y 90 DOTA anti-CEA monoclonal antibody M5A [ Time Frame: 6 months after completion of treatment ] [ Designated as safety issue: No ]
  • Evaluation of radiation doses to whole body, normal organs, and tumor through serial nuclear imaging [ Time Frame: 1 month after completion of study treatment ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 25
Study Start Date: March 2011
Estimated Primary Completion Date: October 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (combination chemotherapy and radioimmunotherapy)
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
Given IV
Other Names:
  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • L-OHP
Drug: leucovorin calcium
Given IV
Other Names:
  • CF
  • CFR
  • LV
Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Radiation: yttrium Y 90 DOTA anti-CEA monoclonal antibody M5A
Given IV
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Drug: irinotecan hydrochloride
Given IV
Other Names:
  • Campto
  • Camptosar
  • CPT-11
  • irinotecan
  • U-101440E

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the progression free survival in colorectal cancer patients after hepatic resection of liver metastases and FOLFOX or leucovorin calcium, fluorouracil, and irinotecan hydrochloride (FOLFIRI) chemotherapy [+/- Bevacizumab], or capecitabine and oxaliplatin (XELOX),followed by intravenous (IV) yttrium-90 (90Y) M5A anti-CEA antibody.

SECONDARY OBJECTIVES:

I. To study the feasibility and toxicities of such adjuvant therapy following resection and/or ablation of liver metastases and FOLFOX chemotherapy.

II. To evaluate the biodistribution, clearance and metabolism of 90Y and 111In (indium-111) M5A administered IV.

OUTLINE:

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.

RADIOIMMUNOTHERAPY (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.

After completion of study treatment, patients are followed up at 3 and 6 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • 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
  • If a patient has previously received murine or chimeric antibody, then serum anti-antibody testing must be negative
  • Computed tomography (CT) scan restaging done prior to RIT must demonstrate no evidence of progressive disease
  • The patient must be seen in consultation by the radiation oncologist who will be administering the radiolabeled antibody therapy and must be informed of the potential risks and side effects of the therapy, and informed consent must be documented in the consultation note

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01320683

Locations
United States, California
City of Hope Medical Center
Duarte, California, United States, 91010
Sponsors and Collaborators
City of Hope Medical Center
Investigators
Principal Investigator: Jeffrey Wong City of Hope Medical Center
  More Information

No publications provided

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT01320683     History of Changes
Other Study ID Numbers: 09053, NCI-2011-00369, P01CA043904
Study First Received: March 18, 2011
Last Updated: July 17, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasm Metastasis
Rectal Neoplasms
Colonic Neoplasms
Liver Neoplasms
Neoplastic Processes
Neoplasms
Pathologic Processes
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Colonic Diseases
Liver Diseases
Antibodies
Immunoglobulins
Fluorouracil
Antibodies, Monoclonal
Bevacizumab
Oxaliplatin
Irinotecan
Camptothecin
Leucovorin
Levoleucovorin
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 16, 2014