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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

Primary Purpose

Liver Metastases, Recurrent Colon Cancer, Recurrent Rectal Cancer

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
oxaliplatin
leucovorin calcium
fluorouracil
bevacizumab
yttrium Y 90 DOTA anti-CEA monoclonal antibody M5A
laboratory biomarker analysis
pharmacological study
irinotecan hydrochloride
Sponsored by
City of Hope Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Liver Metastases

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
  • 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

Sites / Locations

  • City of Hope Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (combination chemotherapy and radioimmunotherapy)

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Overall Survival
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.

Full Information

First Posted
March 18, 2011
Last Updated
June 17, 2016
Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT01320683
Brief Title
Combination Chemotherapy and Bevacizumab Before Surgery and Radiolabeled Monoclonal Antibody Therapy in Treating Liver Metastases in Patients With Metastatic Colorectal Cancer
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2016
Overall Recruitment Status
Terminated
Why Stopped
Slow accrual.
Study Start Date
March 2011 (undefined)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
December 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
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Liver Metastases, Recurrent Colon Cancer, Recurrent Rectal Cancer, Stage IVA Colon Cancer, Stage IVA Rectal Cancer, Stage IVB Colon Cancer, Stage IVB Rectal Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
1 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (combination chemotherapy and radioimmunotherapy)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
oxaliplatin
Other Intervention Name(s)
1-OHP, Dacotin, Dacplat, Eloxatin, L-OHP
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
leucovorin calcium
Other Intervention Name(s)
CF, CFR, LV
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
fluorouracil
Other Intervention Name(s)
5-fluorouracil, 5-Fluracil, 5-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, 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
Intervention Type
Other
Intervention Name(s)
pharmacological study
Other Intervention Name(s)
pharmacological studies
Intervention Description
Correlative studies
Intervention Type
Drug
Intervention Name(s)
irinotecan hydrochloride
Other Intervention Name(s)
Campto, Camptosar, CPT-11, irinotecan, U-101440E
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Progression-free Survival
Description
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.
Time Frame
Up to 24 months
Secondary Outcome Measure Information:
Title
Overall Survival
Description
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.
Time Frame
Up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeffrey Wong
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

Plan to Share IPD
No

Learn more about this trial

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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