Trials Sponsors Conditions Drugs Pricing

Brief Summary

Background:

Many cancers produce two proteins, carcinoembryonic antigen (CEA) and mucin-1 (MUC-1).
The PANVAC-V (PANVAC vaccinia) priming vaccine and PANVAC-F (PANVAC fowlpox) boosting vaccine contain human genes that cause production of CEA and MUC-1, which can be used as a target for the immune system to attack the cancer. The vaccines also contain genes that cause production of other proteins that enhance immune activity.
Sargramostim is a protein that boosts the immune system. Objectives:
To evaluate the safety and effectiveness of PANVAC-V and PANVAC-F in patients with advanced cancer.
To document the immune response to the vaccines and any anti-tumor responses that may occur. Eligibility: Patients 18 years of age and older with advanced cancer whose tumors produce CEA or MUC-1 protein Design:
This trial has three cohorts: the first cohort includes 10 patients with advanced colorectal cancer and 10 to 15 patients with any advanced non-colorectal cancer that produces either EA or mitochondrial Ca2+ uniporter 1 (MCU-1); the second cohort includes 12 patients with advanced breast cancer and the third cohort includes 14 patients with advanced ovarian cancer.
All patients receive PANVAC-V on study day 1, followed by PANVAC-F on days 15, 29 and 43 then every 28 days for up to 12 vaccines followed by every 3 months until disease progression or toxicity. The vaccines are given by injection under the skin. Sargramostim is injected at the vaccination site on the day of each vaccination and for the next 3 days following vaccination.
Patients whose scans show that their disease has progressed, but who are otherwise clinically stable may revert back to monthly injections.
Patients undergo apheresis to collect white blood cells (lymphocytes) on day 1 and day 71 of the study to measure the immune response to the treatment. Blood is collected through a needle placed in one arm and directed through a cell separator machine where the lymphocytes are extracted. The rest of the blood components are returned to the patient through the same needle.
Patients are monitored with frequent blood tests and periodic imaging tests (scans) to monitor for safety and the response to treatment.

Conditions

Adenocarcinoma Breast Cancer Colorectal Cancer Ovarian Cancer

Keywords

CEAVaccineImmunotherapyMUC-1CancerAdenocarcinomaMetastatic Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

Number of Participants With Complete Responses (CRs), Partial Responses (PRs,) Stable Disease and Progressive Disease in the Ovarian Cancer and Breast Cancer Cohorts
Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response is disappearance of all clinical and laboratory signs and symptoms of disease for a minimum of 4 weeks during which no new lesions may appear. Partial Response is a minimum of 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. Stable disease is neither sufficient shrinkage to qualify for partial response nor progressive disease, taking as reference the smallest sum longest diameter since the treatment started. Progressive disease is a minimum of 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new measurable lesions.
Approximately 6 months while on trial
Percentage of Vaccines Associated With Grade 1 and Grade 2 Adverse Events Related to Vaccine in the Colorectal Cancer and Non-Colorectal Cancer Arm/Group
Grade 1 (mild) and Grade 2 (moderate) adverse events were assessed by the Common Terminology Criteria in Adverse Events (CTCAE) v3.0 if reported prior to August 1, 2010 and CTCAE v4.0 if reported after. A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Study Arms (1)

All Cohorts: Colorectal, Non-Colorectal, Breast, and Ovarian

EXPERIMENTAL

All cohorts receive the same intervention (Cohort 1: Colorectal arm, non-colorectal cancers; Cohort 2: breast cancer; Cohort 3: ovarian cancers)

Biological: PANVAC-VBiological: PANVAC-FDrug: Sargramostim (GM-CSF, Leukine)

Interventions

PANVAC-VBiological

Patients receive 2 x 10(8) pfu PANVAC-V (vaccinia) subcutaneously on Day 1.

All Cohorts: Colorectal, Non-Colorectal, Breast, and Ovarian

PANVAC-FBiological

Patients receive 1 x 10(9) pfu PANVAC-F (fowlpox) or about days 15, 29, and 43 then every month for 12 doses then every 3 months until disease progression or toxicity.

All Cohorts: Colorectal, Non-Colorectal, Breast, and Ovarian

Eligibility Criteria

Age18 Years - 100 Years

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

A. Histologically confirmed carcinoma that for patients in the first cohort (colorectal and non-colorectal cancer) is carcinoembryonic antigen (CEA) or mucin-1 (MUC-1) positive. Tumor that has been shown to express CEA or MUC-1 (greater than or equal to 20 % of cells) by immunohistochemical techniques or patients that have had an elevated serum CEA (greater than 5 microgram/L) at any point during their disease course. For patients in the ovarian and breast cancer cohorts, as greater than 95% of these express MUC-1 or CEA, we will not require staining prior to coming onto trial.

Sponsors & Collaborators

National Cancer Institute (NCI)
NIHlead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Related Publications (5)

Madan RA, Bilusic M, Heery C, Schlom J, Gulley JL. Clinical evaluation of TRICOM vector therapeutic cancer vaccines. Semin Oncol. 2012 Jun;39(3):296-304. doi: 10.1053/j.seminoncol.2012.02.010.
PMID: 22595052BACKGROUND
Madan RA, Arlen PM, Gulley JL. PANVAC-VF: poxviral-based vaccine therapy targeting CEA and MUC1 in carcinoma. Expert Opin Biol Ther. 2007 Apr;7(4):543-54. doi: 10.1517/14712598.7.4.543.
PMID: 17373905BACKGROUND
Mohebtash M, Tsang KY, Madan RA, Huen NY, Poole DJ, Jochems C, Jones J, Ferrara T, Heery CR, Arlen PM, Steinberg SM, Pazdur M, Rauckhorst M, Jones EC, Dahut WL, Schlom J, Gulley JL. A pilot study of MUC-1/CEA/TRICOM poxviral-based vaccine in patients with metastatic breast and ovarian cancer. Clin Cancer Res. 2011 Nov 15;17(22):7164-73. doi: 10.1158/1078-0432.CCR-11-0649. Epub 2011 Nov 8.

MeSH Terms

Conditions

AdenocarcinomaColorectal NeoplasmsOvarian NeoplasmsBreast NeoplasmsNeoplasms

Interventions

sargramostimGranulocyte-Macrophage Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

CarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeIntestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by Site

Results Point of Contact

Title: Dr. James Gulley
Organization: National Cancer Institute

Study Officials

James L Gulley, M.D.
National Cancer Institute (NCI)
PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee: No
Restrictive Agreement: No

Enrollment

51 participants (actual enrollment reported by the registry).

Study Design

Study Type: interventional
Phase: phase 1 2
Masking: NONE
Purpose: TREATMENT
Intervention Model: SEQUENTIAL
Sponsor Type: NIH
Responsible Party: PRINCIPAL INVESTIGATOR
PI Title: Principal Investigator

Study Record Dates

First Submitted

July 23, 2004

First Posted

July 26, 2004

Study Start

July 21, 2004

Actual (reported)

You may not qualify if:

A. Patients should have no evidence of being immunocompromised as listed below.
Human immunodeficiency virus positivity due to the potential for decreased tolerance and risk for severe side effects
Active autoimmune diseases requiring treatment or a history of autoimmune disease that might be stimulated by vaccine treatment. This requirement is due to the potential risks of exacerbating autoimmunity. Patients with endocrine disease that is controlled by replacement therapy including thyroid disease and adrenal disease and vitiligo may be enrolled.
B. Concurrent use of systemic steroids, except for physiologic doses for systemic steroid replacement or local (topical, nasal, or inhaled) steroid use. Limited doses systemic steroids to prevent intravenous (IV) contrast, allergic reaction, or anaphylaxis (in patients who have known contrast allergies) are allowed.
C. History of allergy or untoward reaction to prior vaccination with vaccinia virus.
D. Pregnant or breast-feeding women.
E. Altered immune function, including immunodeficiency or history of immunodeficiency; eczema; history of eczema, or other eczematoid skin disorders; or those with acute, chronic or exfoliative skin conditions (e.g. atopic dermatitis, burns, impetigo, varicella zoster, severe acne, or other open rashes or wounds).
F. Serious intercurrent medical illness which would interfere with the ability of the patient to carry out the treatment program, including, but not limited to, inflammatory bowel disease, Crohn's disease, ulcerative colitis, or active diverticulitis
G. Patients with a history of cardiomyopathy or symptomatic congestive heart failure (unless stable on treatment), symptomatic arrhythmia not controlled by medication. Unstable atherosclerotic heart disease (e.g. unstable angina) who require active intervention and history of myocardial infarction or embolic stroke within the past 6 months.
H. Clinically active brain metastasis, or a history of encephalitis, multiple sclerosis, or seizures within the last year (from seizure disorder or brain metastasis).
I. Medical conditions, which, in the opinion of the investigators would jeopardize the patient or the integrity of the data obtained.
J. Concurrent chemotherapy; an exception to this is to allow for patients with breast cancer who are receiving trastuzumab, to continue therapy with trastuzumab while receiving the vaccine treatment.
K. Serious hypersensitivity reaction to egg products.
L. Clinically significant cardiomyopathy requiring treatment.
M. Chronic hepatitis infection, including B and C, because of potential immune impairment.
+2 more criteria

PANVAC-V and PANVAC-F Vaccines Plus Sargramostim to Treat Advanced Cancer

Brief Summary

Registry Overview

Trial Relationships

Study Timeline

Study Start

First Submitted

First Posted

Primary Completion

Study Completion

Results Posted

Conditions

Keywords

Outcome Measures

Primary Outcomes (2)

Study Arms (1)

All Cohorts: Colorectal, Non-Colorectal, Breast, and Ovarian

Interventions

Eligibility Criteria

You may qualify if:

Sponsors & Collaborators

Study Sites (1)

Related Publications (5)

MeSH Terms

Conditions

Interventions

Condition Hierarchy (Ancestors)

Results Point of Contact

Study Officials

Publication Agreements

Enrollment

Study Design

Study Record Dates

Secondary Outcomes (4)

You may not qualify if:

Intervention Hierarchy (Ancestors)

Data Sharing

Source record

Documents

Locations

PANVAC-V and PANVAC-F Vaccines Plus Sargramostim to Treat Advanced Cancer

Brief Summary

Registry Overview

Trial Relationships

Related Scientific Literature

Study Timeline

Study Start

First Submitted

First Posted

Primary Completion

Study Completion

Results Posted

Conditions

Keywords

Outcome Measures

Primary Outcomes (2)

Study Arms (1)

All Cohorts: Colorectal, Non-Colorectal, Breast, and Ovarian

Interventions

Eligibility Criteria

You may qualify if:

Sponsors & Collaborators

Study Sites (1)

Related Publications (5)

MeSH Terms

Conditions

Interventions

Condition Hierarchy (Ancestors)

Results Point of Contact

Study Officials

Publication Agreements

Enrollment

Study Design

Study Record Dates

Secondary Outcomes (4)

You may not qualify if:

Intervention Hierarchy (Ancestors)

Data Sharing

Source record

Documents

Locations