PANVAC-V and PANVAC-F Vaccines Plus Sargramostim to Treat Advanced Cancer
This study is ongoing, but not recruiting participants.
Information provided by:
National Institutes of Health Clinical Center (CC)
First received: July 23, 2004
Last updated: January 3, 2014
Last verified: June 2013
- Many cancers produce two proteins, carcinoembryonic antigen (CEA) and mucin-1 (MUC-1).
- The PANVAC-V priming vaccine and PANVAC-F 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.
- 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
- This trial has four arms: the first arm includes 10 patients with advanced colorectal cancer; the second arm includes 10 to 15 patients with any advanced non-colorectal cancer that produces either EA or MCU-1; the third arm includes about 12 patients with advanced breast cancer; the fourth arm includes about 12 patients with advanced ovarian cancer.
- All patients receive PANVAC-V on study day 1, followed by PANVAC-F on days 15, 29 and 43. 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 disease has not worsened after the last boosting vaccination may receive up to 12 additional monthly boosting vaccinations. Following the 12 vaccinations, patients may receive vaccine every 3 months. 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.
Drug: PANVAC-V [Recombinant-Vaccinia-CEA (D609)/MUC-1(L93)/TRICOM]
Drug: PANVAC-F [Recombinant-Fowlpox-CEA (D609)/MUC-1(L93)/TRICOM]
Drug: Leukine (Sargramostim)
|Study Design:||Primary Purpose: Treatment|
|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|
Resource links provided by NLM:
Drug Information available for: Metronidazole Metronidazole benzoate Metronidazole hydrochloride SargramostimU.S. FDA Resources
Further study details as provided by National Institutes of Health Clinical Center (CC):
Primary Outcome Measures:
- For the Ovarian Cancer and Breast Cancer arms: To evaluate clinical response to the vaccine.
Secondary Outcome Measures:
- To evaluate immune response generated by this combination therapy as measure by ELISPOT assay.
|Study Start Date:||July 2004|
|Estimated Study Completion Date:||December 2014|
Intervention Details:Detailed Description:
Drug: PANVAC-V [Recombinant-Vaccinia-CEA (D609)/MUC-1(L93)/TRICOM]
N/ADrug: PANVAC-F [Recombinant-Fowlpox-CEA (D609)/MUC-1(L93)/TRICOM]
N/ADrug: Leukine (Sargramostim)
- CEA and 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 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 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
- For the first two arms (colorectal cancer and non-colorectal cancer): 1 To evaluate the safety and tolerability of the vaccine. 2 To document any objective anti-tumor responses that may occur
- For the Ovarian Cancer and Breast Cancer arms: 1 To evaluate clinical response to the vaccine. 2 To evaluate the safety and tolerability of the vaccine
- 2 (all arms) To evaluate immune response generated by this combination therapy as measured by ELISPOT assay
- In the first two arms (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 arms, patients must have evaluable disease
- Normal organ function, ECOG 0-1
- This is a non-randomized four arm, pilot trial of pox viral vaccines that contain the transgenes for CEA and MUC-1 (both with modified HLA-A2 agonist epitopes) as well as 3 human T-cell costimulatory molecules, B7-1, ICAM-1, and LFA-3 [PANVAC(TM)-V (vaccinia) and PANVAC(TM)-F (fowlpox)] in patients with metastatic carcinoma that express CEA or MUC-1 antigen.
- The first arm will enroll 10 patients with metastatic colorectal adenocarcinoma.
- The second arm will consist of 10-15 patients with any metastatic non-colorectal carcinoma that expresses either CEA or MUC-1.
- The third arm will consist of about 12 patients with metastatic breast carcinoma. The fourth arm will consist of about 12 patients with metastatic ovarian carcinoma.
- All patients will receive 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 (Core Phase).
- Sargramostim (100 micro g) will be given at the site of the vaccination on each vaccination day and for three consecutive days thereafter.
- Up to 12 additional monthly boosting vaccinations (Extension Phase) will be offered to patients who have completed the Core Phase of the study and who have not experienced disease progression.
- Following the 12 monthly vaccinations, patients without disease progression will be allowed to receive vaccine every 3 months.
- Patients who have radiographic evidence of progressive disease, but who are otherwise clinically stable may revert back to monthly vaccinations.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00088413
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
Sponsors and Collaborators
|Principal Investigator:||James L Gulley, M.D.||National Cancer Institute (NCI)|