Safety Study of Human MUC-1 (Mucin-1) Adenoviral Vector Vaccine for Immunotherapy of Epithelial Cancers

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified May 2014 by Singapore Clinical Research Institute
Sponsor:
Collaborators:
MicroVAX, LLC
ClinDatrix, Inc
Information provided by (Responsible Party):
Singapore Clinical Research Institute
ClinicalTrials.gov Identifier:
NCT02140996
First received: May 8, 2014
Last updated: May 16, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Epithelial Cancers of the Lung, Breast, Ovary, Prostate and Colon
Drug: Ad-sig-hMUC-1/ecdCD40L vector vaccine
Phase 1

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Singapore Clinical Research Institute:

Primary Outcome Measures:
  • 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.


Estimated Enrollment: 24
Study Start Date: June 2014
Estimated Study Completion Date: April 2016
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Men or women age 21 yrs or older with biopsy-proven recurrent or metastatic, measurable or non-measurable adenocarcinoma of the breast, ovary, lung, colon or prostate.
  2. Elevated serum MUC-1 levels [as measured by Carcinoma Antigen (CA) 15-3 or CA27.29] at any time since the diagnosis of cancer (levels do not need to be elevated at the time of trial entry).
  3. Received at least one line of palliative chemotherapy.
  4. No chemotherapy and/or radiation therapy for at least 28 days before consent.
  5. An echocardiogram that shows a left ventricular ejection fraction greater than or equal to the lower limits of normal.
  6. Electrocardiogram (ECG) with no evidence of ischemia or infarction.
  7. Ability to understand the study's risks, benefits, and procedures and provide written informed consent.
  8. Performance status <2 on the Eastern Cooperative Oncology Group (ECOG) performance scale and life expectancy of greater than 12 months.
  9. Acceptable pulmonary function. (If questionable a pulmonary function test will be performed.)
  10. Negative serology for hepatitis B [hepatitis B surface antigen (HBsAg) negative], hepatitis C and human immunodeficiency virus (HIV).
  11. All of the following: white blood count >3500, absolute neutrophil count >/= 1,500, hemoglobin > 8 g/dL, platelet count > 100,000/dL: Bilirubin <1.5, AST (aspartate aminotransferase), ALT (alanine aminotransferase), LDH (Lactate dehydrogenase) < 2 times the upper limit of normal, and calculated creatinine clearance >/= 50 mls/min.
  12. For women with child-bearing potential: negative urinary pregnancy test at screening and within 7 days of enrollment; for men or women: willingness to use an approved contraceptive method while participating in this trial. Documentation of type of contraception patient will be using must be included in screening visit note by investigator.

Exclusion Criteria:

  1. History of bronchospasm or asthma that requires steroid treatment (inhaled or oral).
  2. Treatment with steroid (for any condition, except for chemotherapy premedication or emesis) within 28 days of trial registration.
  3. Current anti-cancer treatment with doxorubicin (Adriamycin), lapatinib, trastuzumab, bevacizumab or other monoclonal antibody therapy. Patients must be off these therapies for at least 28 days. Patients may have been exposed to chemotherapy or radiation therapy 4 weeks prior to receiving the vaccination.
  4. Current anti-cancer treatment with tamoxifen. Patients must be off tamoxifen for at least 28 days prior to enrollment. (Aromatase inhibitors and raloxifene are allowed).
  5. History of any autoimmune disease such as lupus, rheumatoid arthritis or psoriasis.
  6. Uncontrolled diabetes mellitus.
  7. Unable or unwilling to undergo repeated clinical evaluations and other diagnostic procedures or unable to sign an informed consent.
  8. History of other malignancies except squamous or basal cell carcinomas of the skin or cervical carcinoma in situ.
  9. History of organ transplant or allogeneic bone marrow transplants.
  10. Pregnant or nursing females.
  11. Any acute or chronic viral, bacterial, or fungal infection which requires specific therapy. Acute therapy must be completed within 14 days prior to study treatment.
  12. Any underlying conditions which would contraindicate therapy with study treatment (or allergies to reagents used in the study treatment).
  13. Any history of cardiac disease including arrhythmia (requiring active treatment or medications), heart failure, angina, infarction or coronary artery disease.
  14. History of hypercoagulable disorder including history of prior pulmonary embolism, antiphospholipid antibody syndrome, deep venous thrombosis [except for indwelling intravenous catheter associated DVT (deep vein thrombosis), as long as patient has completed anticoagulation therapy].
  15. Any brain or leptomeningeal involvement by the cancer.
  16. Known Ornithine transcarbamylase deficiency.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02140996

Contacts
Contact: Han Chong Toh, MD +65 64368174 hanchongtoh@gmail.com

Locations
Singapore
National Cancer Centre Singapore Not yet recruiting
Singapore, Singapore, 169610
Contact: Hui Shan Chong    +65 64368431    chong.hui.shan@ncc.com.sg   
Contact: Lishan Low    +65 6436 8276    Low.Lishan@ncc.com.sg   
Principal Investigator: Han Chong Toh, MD         
Sponsors and Collaborators
Singapore Clinical Research Institute
MicroVAX, LLC
ClinDatrix, Inc
Investigators
Principal Investigator: Han Chong Toh, MD National Cancer Centre, Singapore
  More Information

No publications provided

Responsible Party: Singapore Clinical Research Institute
ClinicalTrials.gov Identifier: NCT02140996     History of Changes
Other Study ID Numbers: MUC-1
Study First Received: May 8, 2014
Last Updated: May 16, 2014
Health Authority: United States: Food and Drug Administration
Singapore: Health Sciences Authority

Keywords provided by Singapore Clinical Research Institute:
MUC-1 vector vaccine; epithelial cancers; immunotherapy; safety

Additional relevant MeSH terms:
Lung Neoplasms
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms

ClinicalTrials.gov processed this record on October 22, 2014