Epithelial Cancers of the Lung, Breast, Ovary, Prostate and ColonPhase 1MUC-1NCT02140996
Safety Study of Human MUC-1 (Mucin-1) Adenoviral Vector Vaccine for Immunotherapy of Epithelial Cancers
A Phase 1 study testing Ad-sig-hMUC-1/ecdCD40L vector vaccine in people with Epithelial Cancers of the Lung, Breast, Ovary, Prostate and Colon, run by Singapore Clinical Research Institute at 2 sites in Singapore.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Epithelial Cancers of the Lung, Breast, Ovary, Prostate and Colon
- What is being tested?
- Ad-sig-hMUC-1/ecdCD40L vector vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 2 sitesSingapore
- Study dates
- Sep 2014to Jun 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- 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).
- Received at least one line of palliative chemotherapy.
- No chemotherapy and/or radiation therapy for at least 28 days before consent.
- An echocardiogram that shows a left ventricular ejection fraction greater than or equal to the lower limits of normal.
- Electrocardiogram (ECG) with no evidence of ischemia or infarction.
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- Ability to understand the study's risks, benefits, and procedures and provide written informed consent.
- Performance status <2 on the Eastern Cooperative Oncology Group (ECOG) performance scale and life expectancy of greater than 12 months.
- Acceptable pulmonary function. (If questionable a pulmonary function test will be performed.)
- Negative serology for hepatitis B [hepatitis B surface antigen (HBsAg) negative], hepatitis C and human immunodeficiency virus (HIV).
- 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.
- 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.
Who cannot join
- History of bronchospasm or asthma that requires steroid treatment (inhaled or oral).
- Treatment with steroid (for any condition, except for chemotherapy premedication or emesis) within 28 days of trial registration.
- 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.
- 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).
- History of any autoimmune disease such as lupus, rheumatoid arthritis or psoriasis.
- Uncontrolled diabetes mellitus.
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- Unable or unwilling to undergo repeated clinical evaluations and other diagnostic procedures or unable to sign an informed consent.
- History of other malignancies except squamous or basal cell carcinomas of the skin or cervical carcinoma in situ.
- History of organ transplant or allogeneic bone marrow transplants.
- Pregnant or nursing females.
- 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.
- Any underlying conditions which would contraindicate therapy with study treatment (or allergies to reagents used in the study treatment).
- Any history of cardiac disease including arrhythmia (requiring active treatment or medications), heart failure, angina, infarction or coronary artery disease.
- 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].
- Any brain or leptomeningeal involvement by the cancer.
- Known Ornithine transcarbamylase deficiency.
Trial locations and contacts
2 sites in 1 country.
Singapore2 sites, 2 recruiting
- Recruiting
National Cancer Centre Singapore
Singapore, 169610
Hui Shan Chong, +65 64368431, chong.hui.shan@ncc.com.sg
Lishan Low, +65 6436 8276, Low.Lishan@ncc.com.sg
- Recruiting
National Cancer Centre
Singapore
Hui Shan Choon, chong.hui.shan@nccs.com.sg
About this study
Official title: Ad-sig-hMUC-1/ecdCD40L 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 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.
- Being tested
- Ad-sig-hMUC-1/ecdCD40L vector vaccine
- Keywords
- MUC-1 vector vaccine; epithelial cancers; immunotherapy; safety; antigen specific vaccine, dendritic cell activation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ad-sig-hMUC-1/ecdCD40L vector vaccineDrug
| Study group | Role | What they receive |
|---|---|---|
| Ad-sig-hMUC-1/ecdCD40L vector vaccine | Experimental | 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. Receives: Drug: Ad-sig-hMUC-1/ecdCD40L vector vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of a safe, tolerable, and immunologically active dose level of the Ad-sig-hMUC-1/ecdCD40L vector vaccine
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.
Measured: Subjects will be followed up to 12 weeks after vaccine injection.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2014 (estimated)
- Study startSep 2014
- Primary completionMar 2017 (estimated)
- Study completionJun 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Epithelial Cancers of the Lung, Breast, Ovary, Prostate and ColonStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Singapore Clinical Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- MicroVAX, LLC, ClinDatrix, Inc.
- Responsible party
- Sponsor
- Investigators
- Han Chong Toh, MD, Principal investigator, National Cancer Centre, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02140996
- Sponsor's protocol ID
- MUC-1
- Acronym
- MUC-1
- Status last verified
- Oct 2016
- First submitted
- 8 May 2014
- Last updated
- 14 Oct 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ad-sig-hMUC-1/ecdCD40L Vector Vaccine for Immunotherapy of Epithelial Cancers
- ClinicalTrials.gov ID
- NCT02140996
- Acronym / sponsor ID
- MUC-1 / MUC-1
- Keywords
- MUC-1 vector vaccine; epithelial cancers; immunotherapy; safety; antigen specific vaccine, dendritic cell activation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Singapore Clinical Research InstituteUniversity, hospital or other
- Collaborators
- MicroVAX, LLC, ClinDatrix, Inc.
- Study start
- Sep 2014
- Primary completion
- Mar 2017 (estimated)
- Study completion
- Jun 2017 (estimated)
- First posted
- 16 May 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ad-sig-hMUC-1/ecdCD40L vector vaccine | Experimental | Drug: Ad-sig-hMUC-1/ecdCD40L vector vaccineExperimental: 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. |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
- 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).
- Received at least one line of palliative chemotherapy.
- No chemotherapy and/or radiation therapy for at least 28 days before consent.
- An echocardiogram that shows a left ventricular ejection fraction greater than or equal to the lower limits of normal.
Key exclusion criteria (16 listed)
- History of bronchospasm or asthma that requires steroid treatment (inhaled or oral).
- Treatment with steroid (for any condition, except for chemotherapy premedication or emesis) within 28 days of trial registration.
- 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.
- 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).
- History of any autoimmune disease such as lupus, rheumatoid arthritis or psoriasis.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ad-sig-hMUC-1/ecdCD40L vector vaccine | Drug | Ad-sig-hMUC-1/ecdCD40L vector vaccine |
Primary outcome
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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Han Chong Toh, MD principal investigator
National Cancer Centre, Singapore
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ad-sig-hMUC-1/ecdCD40L vector vaccine in people with Epithelial Cancers of the Lung, Breast, Ovary, Prostate and Colon, run by Singapore Clinical Research Institute at 2 sites in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 14 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Han Chong Toh, MD (+65 64368174, hanchongtoh@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2016.