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
|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: Subjects will be followed up to 12 weeks after vaccine injection. ] [ Designated as safety issue: Yes ]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:||February 2017|
|Estimated Primary Completion Date:||November 2016 (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|