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

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ClinicalTrials.gov Identifier: NCT01320683
Recruitment Status : Terminated (Slow accrual.)
First Posted : March 22, 2011
Results First Posted : June 20, 2016
Last Update Posted : July 19, 2016
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
City of Hope Medical Center

March 18, 2011
March 22, 2011
May 11, 2016
June 20, 2016
July 19, 2016
March 2011
December 2014   (Final data collection date for primary outcome measure)
Progression-free Survival [ Time Frame: Up to 24 months ]

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.

  • Progression-free survival [ Time Frame: 1 year after completion of study treatment ]
    First documented evidence of treatment failure measured from the 1st chemotherapy given on study; recurrence is diagnosed by biopsy if at all possible
  • Overall survival [ Time Frame: 1 year after completion of study treatment ]
  • Sites of recurrence [ Time Frame: 1 year after completion of study treatment ]
Complete list of historical versions of study NCT01320683 on ClinicalTrials.gov Archive Site
Overall Survival [ Time Frame: Up to 5 years ]
Overall Survival is calculated for all patients from the date of initial treatment to date of death due to any cause. Patients who were still alive were censored at the date of last follow-up. Survival rates were estimates using the Kaplan-Meier method, and 95% confidence limits calculated for these estimates.
Not Provided
Not Provided
Not Provided
 
Combination Chemotherapy and Bevacizumab Before Surgery and Radiolabeled Monoclonal Antibody Therapy in Treating Liver Metastases in Patients With Metastatic Colorectal Cancer
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
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

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.

Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • 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
    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
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.
Interventions:
  • 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
1
25
December 2014
December 2014   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01320683
09053
NCI-2011-00369 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
P01CA043904 ( U.S. NIH Grant/Contract )
Yes
Not Provided
Plan to Share IPD: No
City of Hope Medical Center
City of Hope Medical Center
National Cancer Institute (NCI)
Principal Investigator: Jeffrey Wong City of Hope Medical Center
City of Hope Medical Center
June 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP