AdenocarcinomaPhase 1/2NCT00088413
PANVAC-V and PANVAC-F Vaccines Plus Sargramostim to Treat Advanced Cancer
A Phase 1/2 study testing PANVAC-V, PANVAC-F and Sargramostim (GM-CSF, Leukine) in people with Adenocarcinoma and Colorectal Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Adenocarcinoma, Colorectal Cancer, Ovarian Cancer
- What is being tested?
- PANVAC-V, PANVAC-F and Sargramostim (GM-CSF, Leukine)
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Jul 2004to 31 May 2018
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- 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.
- 18 years of age or greater.
- All patients enrolled on the colorectal/non-colorectal cohort with colorectal adenocarcinoma cohort must be human leukocyte antigen A2 (HLA-A2) positive.
- At least 10 patients enrolled on the colorectal/non-colorectal cohort with non-colorectal adenocarcinoma cohort must be HLA-A2 positive.
- Patients in the breast cohort and the ovarian cohorts are not required to be HLA-A2 positive.
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- 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.
- Able to understand and give informed consent.
- 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.
- Eastern Oncology Cooperative Group (ECOG) performance status of 0 - 1.
- 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.
- Total bilirubin within the institution limits of normal OR patients with Gilbert's syndrome, a total bilirubin less than or equal to 3.0
- 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.
- Hematological eligibility parameters (within 16 days of starting therapy):
- Granulocyte count greater than or equal to 1,500/mm(3)
- Platelet count greater than or equal to 100,000/mm(3)
- Hemoglobin (Hgb) greater than or equal to 10 Gm/dL
- Prior immune therapy with related vaccinia and fowlpox vaccines or antigen-specific peptides is allowed.
- Men and women must agree to use effective birth control or abstinence during and for a period of 4 months after the last vaccination therapy.
- Patients with prostate cancer must continue to receive gonadotropin-releasing hormone (GnRH) agonist therapy (unless orchiectomy has been done).
- Patients should appear clinically stable (in the opinion of the principal investigator) to complete the full 3 month course of vaccination with an anticipated survival of 6 months or longer.
Who cannot join
- 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.
- 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.
- History of allergy or untoward reaction to prior vaccination with vaccinia virus.
- Pregnant or breast-feeding women.
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- 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).
- 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
- 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.
- Clinically active brain metastasis, or a history of encephalitis, multiple sclerosis, or seizures within the last year (from seizure disorder or brain metastasis).
- Medical conditions, which, in the opinion of the investigators would jeopardize the patient or the integrity of the data obtained.
- 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.
- Serious hypersensitivity reaction to egg products.
- Clinically significant cardiomyopathy requiring treatment.
- Chronic hepatitis infection, including B and C, because of potential immune impairment.
- Although topical steroids are allowed, steroid eye drop are contraindicated.
- Cardiac complications, including recent myocardial infarction or cerebrovascular accident within one year, and/or unstable or uncontrolled angina.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: An Open Label Pilot Study to Evaluate the Safety and Tolerability of PANVAC-V (Vaccinia) and PANVAC-F (Fowlpox) in Combination With Sargramostim in Adults With Metastatic Carcinoma
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.
Read more
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.
Read the detailed description
Background:
- Carcinoembryonic antigen (CEA) and mucin-1 (MUC-1) are overexpressed in multiple adenocarcinomas.
- Pox viral vectors can induce a strong immune response to CEA and MUC-1.
- The use of agonist epitopes within the tumor associated antigen (TAA) can induce a better immune response than native peptides and have been associated with clinical responses
- Heterologous prime and boost regimens are superior in terms of generalizing immune responses; and this may translate into improved clinical responses
- The use of granulocyte-macrophage colony-stimulating factor (GM-CSF) does not add significant toxicity and in pre-clinical models is essential for induction for optimal immune responses.
- It is possible by using vectors directed against TAA that there may be additive or synergistic immune responses and this may be important in overcoming antigenic escape variance
- Evidence of clinical benefit has been noted in some patients treated with this vaccine
Objectives:
- For colorectal cancer and non-colorectal cancer Cohort: To evaluate the safety and tolerability of the vaccine.
- For the Ovarian Cancer and Breast Cancer Cohorts: To evaluate clinical response to the vaccine.
Eligibility:
- In the first cohort (colorectal and non-colorectal cancer), histologically confirmed adenocarcinoma that is CEA or MUC-1 positive described as metastatic disease (measurable or evaluable) or metastatic disease documented by biopsy but not evaluable by imaging (e.g. small volume peritoneal disease)
- For the ovarian and breast cancer cohorts, patients must have evaluable disease
- Normal organ function, Eastern Cooperative Oncology Group (ECOG) 0-1
Design:
- This is a non-randomized three cohort, pilot trial of pox viral vaccines that contain the transgenes for CEA and MUC-1 (both with modified human leukocyte antigen A2 (HLA-A2) agonist epitopes) as well as 3 human T-cell costimulatory molecules, B7-1, ICAM-1 (CD54), and LFA-3 (CD58) [PANVAC(TM)-V (vaccinia) and PANVAC(TM)-F (fowlpox)] in patients with metastatic carcinoma that express CEA or MUC-1 antigen.
- The first cohort will enroll 10 patients with metastatic colorectal adenocarcinoma and 10-15 patients with any metastatic non-colorectal carcinoma that expresses either CEA or MUC-1. .
- The second cohort will enroll 12 patients with metastatic breast carcinoma and 14 patients with metastatic ovarian carcinoma.
- All patients will receive the same vaccines on the same schedule. PANVAC(TM)-V (vaccinia) subcutaneously (s.c.) scheduled on day 1, followed by PANVAC(TM)-F (fowlpox) s.c. scheduled 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.
- Sargramostim (100 micro g) will be given at the site of the vaccination (PANVAC-V and PANVAC-F) on each vaccination day and for three consecutive days thereafter.
- Patients who have radiographic evidence of progressive disease, but who are otherwise clinically stable may revert back to monthly vaccinations.
- Conditions
- Adenocarcinoma, Colorectal Cancer, Ovarian Cancer, Breast Cancer
- Being tested
- PANVAC-V, PANVAC-F, Sargramostim (GM-CSF, Leukine)
- Keywords
- CEA, Vaccine, Immunotherapy, MUC-1, Cancer, Adenocarcinoma, Metastatic Adenocarcinoma
- Medical subject headings
- Adenocarcinoma, Colorectal Neoplasms, Ovarian Neoplasms, Breast Neoplasms, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PANVAC-VBiological
Patients receive 2 x 10(8) pfu PANVAC-V (vaccinia) subcutaneously on Day 1.
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.
Sargramostim (GM-CSF, Leukine)Drug
Also called Granulocyte-macrophage colony-stimulating factor
100g sargramostim will be given subcutaneously at the site of the vaccination on each vaccination day and for three consecutive days thereafter.
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: Biological: PANVAC-V; Biological: PANVAC-F; Drug: Sargramostim (GM-CSF, Leukine) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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
Vaccines were administered to participants and 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. Common Terminology Criteria in Adverse Events. 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.
Measured: 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
Here is the count of participants with serious and non-serious adverse events 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.
Measured: 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
Immune response in human leukocyte antigens (HLA)-A2 positive patients to carcinoembryonic antigen (CEA) was assessed by enzyme-linked immunospot assay (ELISPOT) analysis. A positive immune response was defined as a >2x fold increase in the number of interferon gamma producing cells.
Measured: 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
Immune response in human leukocyte antigens (HLA)-A2 positive patients to carcinoembryonic antigen (CEA) was assessed by enzyme-linked immunospot assay (ELISPOT) analysis. A positive immune response was defined as a >2x fold increase in the number of interferon gamma producing cells.
Measured: post vaccination (up to Day 84)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2004 (estimated)
- Study start21 Jul 2004
- Primary completion1 Apr 2018
- Study completion31 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, James Gulley, M.D., National Institutes of Health Clinical Center (CC)
- Investigators
- James L Gulley, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00088413
- Sponsor's protocol ID
- 040246
- Other IDs
- 04-C-0246
- Status last verified
- Apr 2019
- First submitted
- 23 Jul 2004
- Last updated
- 16 Apr 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 22595052Madan 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.
PubMed 17373905Mohebtash 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.
PubMed 22068656Gulley 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.
PubMed 18483372Gorodetska 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.
PubMed 40443562
Study at a glance
From the registry record, last updated by the sponsor on 16 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label Pilot Study to Evaluate the Safety and Tolerability of PANVAC-V (Vaccinia) and PANVAC-F (Fowlpox) in Combination With Sargramostim in Adults With Metastatic Carcinoma
- ClinicalTrials.gov ID
- NCT00088413
- Acronym / sponsor ID
- 040246
- Conditions
- Adenocarcinoma, Colorectal Cancer, Ovarian Cancer, Breast Cancer
- Keywords
- CEA, Vaccine, Immunotherapy, MUC-1, Cancer, Adenocarcinoma, Metastatic Adenocarcinoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 21 Jul 2004 (actual)
- Primary completion
- 1 Apr 2018 (actual)
- Study completion
- 31 May 2018 (actual)
- First posted
- 26 Jul 2004 (estimated)
- Results
- Posted 16 Apr 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Background:
- Carcinoembryonic antigen (CEA) and mucin-1 (MUC-1) are overexpressed in multiple adenocarcinomas.
- Pox viral vectors can induce a strong immune response to CEA and MUC-1.
- The use of agonist epitopes within the tumor associated antigen (TAA) can induce a better immune response than native peptides and have been associated with clinical responses
- Heterologous prime and boost regimens are superior in terms of generalizing immune responses; and this may translate into improved clinical responses
- The use of granulocyte-macrophage colony-stimulating factor (GM-CSF) does not add significant toxicity and in pre-clinical models is essential for induction for optimal immune responses.
- It is possible by using vectors directed against TAA that there may be additive or synergistic immune responses and this may be important in overcoming antigenic escape variance
- Evidence of clinical benefit has been noted in some patients treated with this vaccine
Objectives:
- For colorectal cancer and non-colorectal cancer Cohort: To evaluate the safety and tolerability of the vaccine.
- For the Ovarian Cancer and Breast Cancer Cohorts: To evaluate clinical response to the vaccine.
Eligibility:
- In the first cohort (colorectal and non-colorectal cancer), histologically confirmed adenocarcinoma that is CEA or MUC-1 positive described as metastatic disease (measurable or evaluable) or metastatic disease documented by biopsy but not evaluable by imaging (e.g. small volume peritoneal disease)
- For the ovarian and breast cancer cohorts, patients must have evaluable disease
- Normal organ function, Eastern Cooperative Oncology Group (ECOG) 0-1
Design:
- This is a non-randomized three cohort, pilot trial of pox viral vaccines that contain the transgenes for CEA and MUC-1 (both with modified human leukocyte antigen A2 (HLA-A2) agonist epitopes) as well as 3 human T-cell costimulatory molecules, B7-1, ICAM-1 (CD54), and LFA-3 (CD58) [PANVAC(TM)-V (vaccinia) and PANVAC(TM)-F (fowlpox)] in patients with metastatic carcinoma that express CEA or MUC-1 antigen.
- The first cohort will enroll 10 patients with metastatic colorectal adenocarcinoma and 10-15 patients with any metastatic non-colorectal carcinoma that expresses either CEA or MUC-1. .
- The second cohort will enroll 12 patients with metastatic breast carcinoma and 14 patients with metastatic ovarian carcinoma.
- All patients will receive the same vaccines on the same schedule. PANVAC(TM)-V (vaccinia) subcutaneously (s.c.) scheduled on day 1, followed by PANVAC(TM)-F (fowlpox) s.c. scheduled 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.
- Sargramostim (100 micro g) will be given at the site of the vaccination (PANVAC-V and PANVAC-F) on each vaccination day and for three consecutive days thereafter.
- Patients who have radiographic evidence of progressive disease, but who are otherwise clinically stable may revert back to monthly vaccinations.
Study design
- Primary purpose
- Treatment
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| All Cohorts: Colorectal, Non-Colorectal, Breast, and Ovarian | Experimental | Biological: PANVAC-V, Biological: PANVAC-F, Drug: Sargramostim (GM-CSF, Leukine)All cohorts receive the same intervention (Cohort 1: Colorectal arm, non-colorectal cancers; Cohort 2: breast cancer; Cohort 3: ovarian cancers) |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- 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.
- 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.
- 18 years of age or greater.
- All patients enrolled on the colorectal/non-colorectal cohort with colorectal adenocarcinoma cohort must be human leukocyte antigen A2 (HLA-A2) positive.
- At least 10 patients enrolled on the colorectal/non-colorectal cohort with non-colorectal adenocarcinoma cohort must be HLA-A2 positive.
Key exclusion criteria (17 listed)
- 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.
- 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.
- History of allergy or untoward reaction to prior vaccination with vaccinia virus.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PANVAC-VPatients receive 2 x 10(8) pfu PANVAC-V (vaccinia) subcutaneously on Day 1. | Biological | All Cohorts: Colorectal, Non-Colorectal, Breast, and Ovarian |
| PANVAC-FPatients 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. | Biological | All Cohorts: Colorectal, Non-Colorectal, Breast, and Ovarian |
| Sargramostim (GM-CSF, Leukine)Also: Granulocyte-macrophage colony-stimulating factor100g sargramostim will be given subcutaneously at the site of the vaccination on each vaccination day and for three consecutive days thereafter. | Drug | All Cohorts: Colorectal, Non-Colorectal, Breast, and Ovarian |
Primary outcome
Number of Participants With Complete Responses (CRs), Partial Responses (PRs,) Stable Disease and Progressive Disease in the Ovarian Cancer and Breast Cancer Cohorts
Time frame: Approximately 6 months while on trial
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.
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
Time frame: Approximately 6 months while on trial
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.
4 secondary outcomes
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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: post vaccination (up to Day 84)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Apr 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22595052Madan 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.
- Background: PubMed 17373905Madan 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.
- Results publication: PubMed 22068656Mohebtash 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.
- Results publication: PubMed 18483372Gulley 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.
- Derived from this study: PubMed 40443562Gorodetska 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James L Gulley, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing PANVAC-V, PANVAC-F and Sargramostim (GM-CSF, Leukine) in people with Adenocarcinoma and Colorectal Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Complete Responses (CRs), Partial Responses (PRs,) Stable Disease and Progressive Disease in the Ovarian Cancer and Breast Cancer Cohorts (time frame: Approximately 6 months while on trial). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00088413, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Apr 2019.