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

Liver Metastases Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01320683
• Other study ID #: 09053
• Secondary ID: NCI-2011-00369P0
• Status: Terminated
• Phase: Phase 2
• First received: March 18, 2011
• Last updated: January 7, 2015
• Start date: March 2011
• Est. completion date: December 2014

Study information

• Verified date: January 2015
• Source: City of Hope Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Liver Metastases
• Liver Neoplasms
• Neoplasm Metastasis
• Rectal Neoplasms
• Recurrent Colon Cancer
• Recurrent Rectal Cancer
• Stage IVA Colon Cancer
• Stage IVA Rectal Cancer
• Stage IVB Colon Cancer
• Stage IVB Rectal Cancer

Intervention

Drug:
• oxaliplatin
Given IV
• leucovorin calcium
Given IV
• fluorouracil
Given IV

Biological:
• bevacizumab
Given IV

Radiation:
• yttrium Y 90 DOTA anti-CEA monoclonal antibody M5A
Given IV

Other:
• laboratory biomarker analysis
Correlative studies
• pharmacological study
Correlative studies

Drug:
• irinotecan hydrochloride
Given IV

Locations

Country	Name	City	State
United States	City of Hope Medical Center	Duarte	California

Sponsors (2)

Lead Sponsor	Collaborator
City of Hope Medical Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival	Estimated using the product-limit method of Kaplan-Meier, and 95% confidence limits calculated for these estimates.	1 year after completion of study treatment	No
Secondary	Overall Survival		6 years after completion of treatment	No
Secondary	Biodistribution		6 months after completion of treatment	No
Secondary	Clearance and metabolism of yttrium Y 90 DOTA anti-CEA monoclonal antibody M5A		6 months after completion of treatment	No
Secondary	Evaluation of radiation doses to whole body, normal organs, and tumor through serial nuclear imaging		1 month after completion of study treatment	Yes