Vaccine Therapy in Treating Patients With Liver or Lung Metastases From Colorectal Cancer

Colorectal Cancer Clinical Trial

Official title:

A Phase II Study of Active Immunotherapy With PANVAC or Autologous, Cultured Dendritic Cells Infected With PANVAC After Complete Resection of Hepatic or Pulmonary Metastases of Colorectal Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00103142
• Other study ID #: Pro00007616
• Secondary ID: DUMC-5883-04-6RO
• Status: Completed
• Phase: Phase 2
• First received: February 7, 2005
• Last updated: October 11, 2015
• Start date: February 2005
• Est. completion date: March 2013

Study information

• Verified date: October 2015
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Vaccines made from a gene-modified virus and a person's white blood cells may make the body build an effective immune response to kill tumor cells. Biological therapies, such as Granulocyte-macrophage colony-stimulating factor (GM-CSF), may stimulate the immune system in different ways and stop tumor cells from growing. Combining different types of biological therapies may kill more tumor cells.

PURPOSE: This randomized phase II trial is studying giving vaccine therapy together with dendritic cells to see how well it works compared to giving vaccine therapy together with GM-CSF in treating patients with liver or lung metastases from colorectal cancer removed by surgery.

Description:

OBJECTIVES:

Primary

• Compare 2-year disease-free survival of patients with completely resected hepatic or pulmonary metastases secondary to colorectal cancer treated with adjuvant vaccine therapy comprising vaccinia-Carcinoembryonic antigen (CEA)-mucin 1 (MUC-1)- Triad of costimulatory molecules TRICOM vaccine (PANVAC-V) and fowlpox-CEA-MUC-1-TRICOM vaccine (PANVAC-F) administered with autologous dendritic cells or with sargramostim (GM-CSF).

Secondary

• Compare the rate and magnitude of immune response, as determined by enzyme-linked immunosorbent spot (ELISpot), in patients treated with these regimens.

OUTLINE: This is a randomized study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo leukapheresis to obtain leukocytes for generation of autologous dendritic cells (DC). Patients then receive autologous DC loaded with vaccinia-CEA-MUC-1-TRICOM (PANVAC-V) vaccine subcutaneously (SC) and intradermally (ID) on day 1 and autologous DC loaded with fowlpox-CEA-MUC-1-TRICOM (PANVAC-F) vaccine subcutaneously (SC) and intradermally (ID) on days 28, 56, and 84.

• Arm II: Patients receive PANVAC-V SC on day 1 and PANVAC-F SC on days 28, 56, and 84. Patients also receive sargramostim (GM-CSF) SC into the same injection site once daily on days 0-3, 28-31, 56-59, and 84-87.

After completion of study treatment, patients are followed for 2 years.

PROJECTED ACCRUAL: A total of 72 patients (36 per treatment arm) will be accrued for this study within 2 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 74
• Est. completion date: March 2013
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed hepatic or pulmonary metastases secondary to adenocarcinoma of the colon and rectum

• Must have undergone complete resection of hepatic or pulmonary metastases with curative intent

• No evidence of gross residual disease after surgery

• One or more resected and ablated lesions allowed provided all gross residual tumor was destroyed by ablation

• Repeated resections of hepatic metastatic disease or resections of extrahepatic metastases prior to resection of the hepatic metastases allowed provided the most recent hepatic metastatic resection included total disease resection and/or ablation

• Must have received at least 2 months of perioperative systemic chemotherapy (including preoperative and/or postoperative chemotherapy) that was completed at least 1 month ago

PATIENT CHARACTERISTICS:

Age

• At least 18

Performance status

• Karnofsky 70-100%

Life expectancy

• At least 6 months

Hematopoietic

• Platelet count = 75,000/mm^3

• Hemoglobin = 8.5 g/dL (transfusion or epoetin alfa allowed)

Hepatic

• Bilirubin = 2.0 mg/dL

• Hepatitis B surface antigen negative

• Hepatitis C antibody negative

• No other serious chronic or acute hepatic disease

Renal

• Creatinine = 1.5 mg/dL OR

• Creatinine clearance > 60 mL/min

Cardiovascular

• No New York Heart Association class III or IV cardiac disease

• No other serious chronic or acute cardiac disease

Pulmonary

• No asthma

• No chronic obstructive pulmonary disease

• No other serious chronic or acute pulmonary disease

Immunologic

• No history of autoimmune disease, including, but not limited to, any of the following:

• Inflammatory bowel disease

• Systemic lupus erythematosus

• Ankylosing spondylitis

• Scleroderma

• Multiple sclerosis

• No human immunodeficiency virus (HIV) infection by enzyme-linked immunosorbent assay (ELISA) and western blot

• Not immunocompromised (by disease or therapy)

• No allergy to eggs or any component of the study vaccine

• No history of allergy or untoward reaction to prior vaccinia (smallpox) vaccination

• No allergy or untoward reaction to sargramostim (GM-CSF)

• No active acute or chronic infection, including urinary tract infection within the past 72 hours

• No inflammatory bowel conditions, including, but not limited to, the following:

• Active infectious enteritis

• Eosinophilic enteritis

• No acute, chronic, or exfoliative skin disorders, including any of the following:

• Extensive psoriasis

• Burns

• Impetigo

• Disseminated zoster

• Varicella zoster

• Severe acne

• Other open rashes or wounds

Other

• Not pregnant or nursing

• Fertile patients must use effective contraception

• Able to avoid close contact or household contact for 3 weeks after each vaccination with the following individuals:

• Children under 5 years of age

• Pregnant or nursing women

• Individuals with prior or concurrent extensive eczema, other eczematoid skin disorders, or other acute or chronic skin conditions

• Immunosuppressed or immunodeficient individuals

• No medical or psychological condition that would preclude study compliance

• No extensive eczema

• No other serious chronic or acute illness that would preclude study participation

• No other malignancy within the past 5 years except nonmelanoma skin cancer, controlled superficial bladder cancer, or previously treated carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No other concurrent immunotherapy

Chemotherapy

• See Disease Characteristics

• No concurrent chemotherapy

Endocrine therapy

• More than 6 weeks since prior and no concurrent steroid therapy

Radiotherapy

• No concurrent radiotherapy

Surgery

• See Disease Characteristics

Other

• No other concurrent immunosuppressants (e.g., azathioprine or cyclosporine)

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms
• Metastatic Cancer
• Neoplasm Metastasis

Intervention

Biological:
• falimarev
Given subcutaneously and intradermally
• inalimarev
Given subcutaneously and intradermally
• sargramostim
Given subcutaneously
• therapeutic autologous dendritic cells
Given subcutaneously and intradermally

Locations

Country	Name	City	State
United States	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon
United States	H. Lee Moffitt Cancer Center and Research Institute at University of South Florida	Tampa	Florida
United States	Lombardi Comprehensive Cancer Center at Georgetown University Medical Center	Washington	District of Columbia
United States	Wake Forest University Baptist Medical Center	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Michael Morse, MD	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recurrence-free Survival at 2 Years	Recurrence-free survival for randomized patients receiving dendritic cells (DC) loaded with PANVAC or PANVAC plus Granulocyte-macrophage colony-stimulating factor (GM-CSF) measured from the date of metastasectomy, with relapse defined as documented disease recurrence at any site.	2 years	No
Secondary	Positive Immune Response as Measured by (Enzyme-linked Immunosorbent Spot) ELISpot Assay	CEA-Specific Immune Responders by enzyme-linked immunosorbent spot (ELISpot). The ELISPOT assay is considered positive for a subject if the mean number of spots with CEA exceeds the number of spots with control by a magnitude of 10 and the difference between CEA and control is statistically significant at a level of p=0.05 by the t-test.	13 weeks	No