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

NCT00088413 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 04024604-C-0246
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

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; Colorectal Cancer; Ovarian Cancer; Breast Cancer

Keywords

CEA; Vaccine; Immunotherapy; MUC-1; Cancer; Adenocarcinoma; Metastatic 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.

  Approximately 6 months while on trial

Secondary Outcomes (4)

• Percentage of Participants With Grade 1 and Grade 2 Adverse Events Possibly, Likely, or Definitely Related to Vaccine in the Breast Cancer and Ovarian Cancer Cohorts

  Approximately 2 months while on trial

• Number of Participants With Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE) v3.0 and v4.0

  Date consent signed to date off study, approximately 164 months and 10 days

• Number of Participants With an Positive Immune Response to Carcinoembryonic Antigen (CEA) Peptide and/or Protein in the Colorectal Cancer and Non-colorectal Cancer Cohort Post Vaccination

  post vaccination (up to Day 84)

• Number of Participants With an Positive Immune Response to Carcinoembryonic Antigen (CEA) Peptide and/or Protein in the Breast Cancer and Ovarian Cancer Cohorts Post Vaccination

  post vaccination (up to Day 84)

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-V; Biological: PANVAC-F; Drug: Sargramostim (GM-CSF, Leukine)

Interventions

PANVAC-V BIOLOGICAL

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

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

PANVAC-F BIOLOGICAL

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

Sargramostim (GM-CSF, Leukine) DRUG

100g sargramostim will be given subcutaneously at the site of the vaccination on each vaccination day and for three consecutive days thereafter.

Also known as: Granulocyte-macrophage colony-stimulating factor

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

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (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.
• B. Patients must have completed at least one fluorouracil (5-FU) containing chemotherapy regimen (e.g. 5-FU/leucovorin (LV) with or without either irinotecan or oxaliplatin) for the colorectal cancer arm, or either failed or not be a candidate for therapy of proven efficacy for non-colorectal, breast, or ovarian cancer.
• C. 18 years of age or greater.
• D. All patients enrolled on the colorectal/non-colorectal cohort with colorectal adenocarcinoma cohort must be human leukocyte antigen A2 (HLA-A2) positive.
• E. At least 10 patients enrolled on the colorectal/non-colorectal cohort with non-colorectal adenocarcinoma cohort must be HLA-A2 positive.
• F. Patients in the breast cohort and the ovarian cohorts are not required to be HLA-A2 positive.
• G. For the colorectal and non-colorectal cancer cohort, patients will be required to have: metastatic disease (measurable or evaluable), metastatic disease documented by biopsy but not evaluable by imaging (e.g. small volume peritoneal disease), and patients with surgically resected metastatic disease at high risk of relapse. For the ovarian cohort and the breast cancer cohort, patients will be required to have evaluable disease.
• H. Able to understand and give informed consent.
• I. Able to avoid close household contact (close household contacts are those who share housing or have close physical contact) for at least three weeks after recombinant vaccinia vaccination with persons with active or a history of eczema or other eczematoid skin disorders; those with other acute, chronic or exfoliative skin conditions (e.g., atopic dermatitis, burns, impetigo, varicella zoster, severe acne, or other open rashes or wounds) until condition resolves; pregnant or nursing women; children 3 years of age and under; and immunodeficient or immunosuppressed persons (by disease or therapy), including human immunodeficiency virus (HIV) infection.
• J. Eastern Oncology Cooperative Group (ECOG) performance status of 0 - 1.
• K. Serum creatinine not above the institution limits of normal, and aspartate aminotransferase (AST) less than or equal to twice the upper limits of normal OR creatinine clearance on a 24 hour urine collection of greater than or equal to 60 mL/min.
• L. Total bilirubin within the institution limits of normal OR patients with Gilbert's syndrome, a total bilirubin less than or equal to 3.0
• M. Recovered completely from any reversible toxicity associated with recent therapy. Typically this is 3-4 weeks for patients who most recently received cytotoxic therapy except for the nitrosoureas and mitomycin C for which 6 weeks is needed for recovery.
• N. Hematological eligibility parameters (within 16 days of starting therapy):
• Granulocyte count greater than or equal to 1,500/mm(3)

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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

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: 22595052 BACKGROUND

• 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: 17373905 BACKGROUND

• 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.

  PMID: 22068656 RESULT

• Gulley JL, Arlen PM, Tsang KY, Yokokawa J, Palena C, Poole DJ, Remondo C, Cereda V, Jones JL, Pazdur MP, Higgins JP, Hodge JW, Steinberg SM, Kotz H, Dahut WL, Schlom J. Pilot study of vaccination with recombinant CEA-MUC-1-TRICOM poxviral-based vaccines in patients with metastatic carcinoma. Clin Cancer Res. 2008 May 15;14(10):3060-9. doi: 10.1158/1078-0432.CCR-08-0126.

  PMID: 18483372 RESULT

• Gorodetska I, Samusieva A, Lahuta T, Ponomarova O, Socha O, Kozeretska I. Exploring New Frontiers: Alternative Breast Cancer Treatments Through Glycocalyx Research. Breast J. 2025 May 22;2025:9952727. doi: 10.1155/tbj/9952727. eCollection 2025.

  PMID: 40443562 DERIVED

MeSH Terms

Conditions

Adenocarcinoma; Colorectal Neoplasms; Ovarian Neoplasms; Breast Neoplasms; Neoplasms

Interventions

sargramostim; Granulocyte-Macrophage Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Dr. James Gulley
• Organization: National Cancer Institute

james_gulley@nih.gov

301-480-8870

Study Officials

• James L Gulley, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• 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
• Primary Completion: April 1, 2018
• Study Completion: May 31, 2018
• Last Updated: April 16, 2019
• Results First Posted: April 16, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)