Safety Study of Human MUC-1 (Mucin-1) Adenoviral Vector Vaccine for Immunotherapy of Epithelial Cancers (MUC-1)
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 through activation of dendritic cells and promotion of antigen specific B cells or antigen specific CD8 effector T cells 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||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (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: Subjects will be followed up to 12 weeks after vaccine injection. ]Traditional 3+3 dose escalation scheme is employed for this trial. This trial has 6 cohorts with 3 subjects for each cohort. Subjects in the 1st cohort will receive the lowest planned dose of the vector, 1 x 10^9 VP. If no patient in the 1st cohort experiences Dose limiting toxicity (DLT), a 2nd cohort will receive 1 dose of 1x10^10 VP. Similarly, if no DLT occurs in the preceding cohorts, the dose escalation will continue with the 3rd cohort receiving 1 dose of 5 x 10^10 VP and the 4th cohort receiving 1 dose of 1x10^11 VP. Following completion of the 4th cohort, the toxicity of adding 1 or 2 booster injections at 7 and 21 days following the 1st vector injection will be tested in the 5th and 6th cohorts. The dose of each of the 2 or 3 vector injections administered in the 5th and 6th cohorts will be the top dose tolerated in the first 4th cohorts. If DLT is encountered in the first 3 patients in cohorts 5 or 6, then additional patients will be added to each of these cohorts.
|Study Start Date:||September 2014|
|Estimated Study Completion Date:||June 2017|
|Estimated Primary Completion Date:||March 2017 (Final data collection date for primary outcome measure)|
Experimental: Ad-sig-hMUC-1/ecdCD40L vector vaccine
Experimental: Ad-sig-hMUC-1/ecdCD40L vector vaccine This trial has six 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 10^9 VP. If none of the patients in the 1st cohort experience Dose limiting toxicity (DLT), a 2nd cohort will receive 1 dose of 1x10^10 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 10^10 VP per injection. The patients in the 4th cohort will receive 1 injection of 1x10^11 if no DLT occurs in the preceding cohort. Additional patients will be added to cohort 5 or 6 if DLTs are encountered in the first 3 patients tested in each of these cohorts.
|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 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|
|National Cancer Centre||Recruiting|
|Contact: Hui Shan Choon firstname.lastname@example.org|
|Principal Investigator:||Han Chong Toh, MD||National Cancer Centre, Singapore|