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
- 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
- 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
- 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
- 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
- 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.
Primary Purpose: Treatment
For the Ovarian Cancer and Breast Cancer arms: To evaluate clinical response to the vaccine.
James L Gulley, M.D.
National Cancer Institute (NCI)
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|