Safety Study of Human MUC-1 (Mucin-1) Adenoviral Vector Vaccine for Immunotherapy of Epithelial Cancers
In epithelial cancer, MUC-1(mucin-1) overexpression is thought to disrupt E-cadherin function, leading to anchorage-independent tumor cell growth and metastases. Elevated levels of MUC-1 expression have been found in patients with epithelial cancers of breast, ovarian, colon and lung. Furthermore, overexpression of MUC-1 is independently correlated with adverse clinical phenotypes, metastases and resistance to chemotherapy. In animal models, suppressing the expression of MUC-1 reduces the rates of growth and metastasis and increases the sensitivity of the cancer to chemotherapy-induced cell death.
In this study, an adenoviral Ad-sig-hMUC-1/ecdCD40L vector encoding a fusion protein in which the hMUC-1 epithelial antigen is attached to the CD40L (CD40 ligand). The preclinical results have also shown that two subcutaneous Ad-sig-hMUC-1/ecdCD40L vector injections can induce immunity which suppresses the growth of hMUC-1 tumor cells in 100% of the vaccinated mice without Interleukin (IL) 2 stimulation being required, this suggests that the Ad-sig-hMUC-1/ecdCD40L vector prime-hMUC-1/ecdCD40L protein boost has the potential to be an effective vaccine in epithelial tumors. Therefore, the safety and tolerability of the Ad-sig-hMUC-1/ecdCD40L vector vaccine will be tested in this phase I non-randomized open label dose escalation trial for men or women with metastatic or recurrent epithelial cancers of the lung, breast, ovary, prostate and colon.
Epithelial Cancers of the Lung, Breast, Ovary, Prostate and Colon
Drug: Ad-sig-hMUC-1/ecdCD40L vector vaccine
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Ad-sig-hMUC-1/ecdCD40L Vector Vaccine for Immunotherapy of Epithelial Cancers|
- Assessment of a safe, tolerable, and immunologically active dose level of the Ad-sig-hMUC-1/ecdCD40L vector vaccine [ Time Frame: Participants will be followed up to 12 weeks after vaccine injection. ] [ Designated as safety issue: Yes ]We are employing the traditional 3+3 dose escalation scheme for this Phase I clinical trial. This trial has four cohorts with three subjects planned for each cohort. Subjects in the first cohort will receive 1 dose of vaccine injection at the lowest planned dose of the vector, 1 x 10^9 VP. If none of the patients in the first cohort experience Dose limiting toxicity (DLT), a second cohort will receive 1 dose of 1x10^10 VP. If none of the patients in the second cohort experience DLT, the dose escalation will continue with the third cohort receiving 1 doses of 5 x 10^10 VP per injection on day 1. The patients in the fourth cohort will receive 1 injection of 1x10^11 if no DLT occurs in the preceding cohort. If DLT occurs in one of the first three patients in a cohort, accrual to that cohort will continue up to a total of 6 patients or until 2 patients experience DLT, whichever comes first. If there are 0 or 1 DLT's experienced in this cohort, accrual to the next cohort will proceed.
|Study Start Date:||September 2014|
|Estimated Study Completion Date:||April 2016|
|Estimated Primary Completion Date:||October 2015 (Final data collection date for primary outcome measure)|
Experimental: Ad-sig-hMUC-1/ecdCD40L vector vaccine
A minimum of 6 and a maximum of 24 subjects will be treated on this trial, depending on toxicities observed. This trial has four cohorts with 3 subjects planned for each cohort. Subjects in the 1st cohort will receive 1 dose of vaccine injection at the lowest planned dose of the vector, 1 x 109 VP. If none of the patients in the 1st cohort experience Dose limiting toxicity (DLT), a 2nd cohort will receive 1 dose of 1x1010 VP. If none of the patients in the 2nd cohort experience DLT, the dose escalation will continue with the 3rd cohort receiving 1 doses of 5 x 1010 VP per injection. The patients in the 4th cohort will receive 1 injection of 1x1011 if no DLT occurs in the preceding cohort.
If 1 patient out of 3 experienced DLT, the cohort will be expanded to 6 patients. If ≤1 DLT out of 6 subjects is observed in this cohort, the study will proceed onto the next dose level. If ≥2 is observed in these 6 patients, the next lower dose cohort will be expanded to 6 patients.
|Drug: Ad-sig-hMUC-1/ecdCD40L vector vaccine|
Please refer to this study by its ClinicalTrials.gov identifier: NCT02140996
|Contact: Han Chong Toh, MD||+65 email@example.com|
|National Cancer Centre||Recruiting|
|Contact: Hui Shan Choon firstname.lastname@example.org|
|National Cancer Centre Singapore||Recruiting|
|Singapore, Singapore, 169610|
|Contact: Hui Shan Chong +65 64368431 email@example.com|
|Contact: Lishan Low +65 6436 8276 Low.Lishan@ncc.com.sg|
|Principal Investigator: Han Chong Toh, MD|
|Principal Investigator:||Han Chong Toh, MD||National Cancer Centre, Singapore|