Head and Neck Squamous Cell CarcinomaPhase 1NCT02544880
PDE5 Inhibition Via Tadalafil to Enhance Anti-Tumor Mucin 1 (MUC1) Vaccine Efficacy in Patients With HNSCC
A Phase 1 study testing Tadalafil, Anti-MUC1 Vaccine and Anti-Influenza Vaccine in people with Head and Neck Squamous Cell Carcinoma and Head and Neck Cancer, run by Donald T. Weed, MD, FACS at 1 site in United States.
Trial summary
The investigators hypothesize that Tadalafil treatment, by lowering Myeloid Derived Suppressor Cells (MDSCs) and regulatory T cells (Tregs), can prime an antitumor immune response and promote a permissive environment that should increase the efficacy of anti-tumor vaccine in a setting of minimal residual disease. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Squamous Cell Carcinoma, Head and Neck Cancer
- What is being tested?
- Tadalafil, Anti-MUC1 Vaccine and Anti-Influenza Vaccine
- Type of treatment
- Vaccines, Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Apr 2016to 8 Jun 2021
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Biopsy-proven recurrent or second primary HNSCC of the oral cavity, oropharynx, hypopharynx or larynx (second primary includes unknown primary)
- Stage III or IV (AJCC, 7th ed., 2010) recurrent or second primary HNSCC (For recurrent tumors, staging is determined by the recurrent stage, not by the original pretreatment stage.)
- Surgically resectable, recurrent or second primary HNSCC
- Prior radiation, with or without prior surgery and/or chemotherapy, to the head and neck for definitive treatment of HNSCC of the oral cavity, oropharynx, hypopharynx or larynx with previously documented complete clinical or radiographic response to initial treatment
- a. Prior radiation and any chemotherapy, must have been completed >4 months prior to biopsy-proven recurrence or second primary site disease
- b. Recurrent or second primary HNSCC arises within the previously irradiated field
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- Age ≥ 18 years
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2 or equivalent scale score. See Appendix D for equivalent scale criteria.
- Acceptable organ function as defined by all of the following:
- Alkaline phosphatase < 4.0 x upper limit of normal (ULN)
- Aspartate transaminase (AST) ≤ 2.5 x ULN
- Alanine transaminase (ALT) ≤ 2.5 x ULN
- calculated Creatinine Clearance ≥ 51ml/min as determined by the Cockcroft-Gault Equation:
- [(140-age) * (Weight in kg) * (0.85, if female)] / (72 * Cr)
- Suitable venous access to allow for all study related blood sampling (safety and research)
- Ability to understand and willingness to sign the written informed consent and Health Insurance Portability and Accountability Act (HIPAA) document/s.
- Biopsy-proven recurrent or second primary HNSCC of the oral cavity, oropharynx, hypopharynx or larynx (second primary includes unknown primary)
- Stage III or IV (AJCC, 7th ed., 2010) recurrent or second primary HNSCC (For recurrent tumors, staging is determined by the recurrent stage, not by the original pretreatment stage.)
- Surgically resectable, recurrent or second primary HNSCC
- Prior radiation with or without prior surgery and/or chemotherapy, to the head and neck for definitive treatment of HNSCC of the oral cavity, oropharynx, hypopharynx or larynx with previously documented complete clinical or radiographic response to initial treatment
- a. Prior radiation and any chemotherapy, must have been completed >4 months prior to biopsy-proven recurrence or second primary site disease
- b. Recurrent or second primary HNSCC arises within the previously irradiated field
- Age ≥18 years
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2 or equivalent scale score.
- Suitable venous access to allow for all study related blood sampling (safety and research)
- Ability to understand and willingness to sign the written informed consent and HIPAA document/s.
Who cannot join
- Salvage surgery is not recommended as per National Comprehensive Cancer Network (NCCN) guidelines, or after multidisciplinary treatment evaluation, including those with surgically unresectable disease at primary site or regional lymph nodes
- Recurrent or second primary AJCC Stage I or II HNSCC (for recurrent tumors, staging is determined by the recurrent stage, not by the original pretreatment stage).
- Distant metastatic disease
- Recurrent or second primary HNSCC of the nasopharynx, paranasal sinuses, or cervical esophagus
- Use of Phosphodiesterase Type 5 (PDE5) inhibitors such as vardenafil (Levitra®), Tadalafil (Cialis®), and sildenafil citrate (Viagra®) ≤15-days prior to (intended) enrollment
- Patients who have the intention to receive non-study PDE5 inhibitors and flu vaccination(s) anytime during the study will be excluded.
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- Prior or known adverse reactions to PDE5 inhibitors, poly-ICLC (Hiltonol®), and prior dose(s) of Influenza vaccine including but not limited to their components
- History of severe or unstable cardiac or cerebrovascular disease:
- a. Myocardial infarction within the last 90 days
- b. Unstable angina or angina occurring during sexual intercourse
- c. New York Heart Association (NYHA) Class 2 or greater heart failure in the last 3 months.
- d. Uncontrolled arrhythmias
- e. Sustained hypotension (<90/50 mmHg) or uncontrolled Hypertension (>170/100 mmHg)
- f. Stroke within the last 6 months
- Therapy with nitrates, alpha-blockers, or cytochrome P450 (CYP3A4) inhibitors within 7-days prior to study treatment initiation and for whom stopping is unsafe and/or a safe substitute is not medically recommended. Some examples are provided in Appendix A.
- Positive Antinuclear Antibody Test (ANA)
- Immunosuppression or immunocompromised for reasons not directly related to patient's malignancy (e.g. HIV or kidney transplant)
- History of severe or life threatening autoimmune diseases [Exceptions: Mild autoimmune diseases determined at the discretion of the Investigator(s), e.g. psoriasis.]
- Unilateral blindness, hereditary retinal disorders, or at an increased risk of blindness
- Unilateral deafness, or severe hearing loss dependent upon hearing aid(s) for serviceable communication
- Female patients who are pregnant or breastfeeding. (Females of childbearing potential are required to have a negative urine β-human chorionic gonadotropin (β-hCG) pregnancy test result obtained during screening; pregnancy testing is not required for post-menopausal or surgically sterilized women.)
- Females of childbearing potential who refuse to practice effective methods of contraception or abstain from heterosexual intercourse from the time of signing the informed consent through 30-days after the last vaccination.
- Serious medical or psychiatric illness/condition, including alcohol or drug abuse likely in the judgment of the Investigator(s) to interfere with compliance to protocol treatment/research.
- Patients of vulnerable populations such as children less than 18 years of age, prisoners, institutionalized individuals or others likely to be vulnerable are not eligible for participation in this study.
- Salvage surgery is not recommended as per NCCN guidelines, or after multidisciplinary treatment evaluation, including those with surgically unresectable disease at primary site or regional lymph nodes
- Recurrent or second primary AJCC Stage I or II HNSCC (for recurrent tumors, staging is determined by the recurrent stage, not by the original pretreatment stage).
- Distant metastatic disease
- Recurrent or second primary HNSCC of the nasopharynx, paranasal sinuses, or cervical esophagus
- Use of PDE5 inhibitors such as vardenafil (Levitra®), Tadalafil (Cialis®), and sildenafil citrate (Viagra®) ≤15-days prior to (intended) enrollment
- Patients who have the intention to receive non-study PDE5 inhibitors and flu vaccination(s) anytime during the study will be excluded.
- Positive Antinuclear Antibody Test (ANA)
- Immunosuppression or immunocompromised for reasons not directly related to patient's malignancy (e.g. HIV or kidney transplant)
- History of severe or life threatening autoimmune diseases [Exceptions: Mild autoimmune diseases determined at the discretion of the Investigator(s), e.g. psoriasis.]
Trial locations and contacts
1 site in 1 country.
About this study
Official title: PDE5 Inhibition Via Tadalafil (Cialis®) to Enhance Anti-Tumor MUC1 Vaccine Efficacy in Patients With Resectable, and Recurrent or Second Primary Head and Neck Squamous Cell Carcinoma (HNSCC): A Phase I/II Clinical Trial
The investigators hypothesize that Tadalafil treatment, by lowering Myeloid Derived Suppressor Cells (MDSCs) and regulatory T cells (Tregs), can prime an antitumor immune response and promote a permissive environment that should increase the efficacy of anti-tumor vaccine in a setting of minimal residual disease.
Read the detailed description
This study is halting accrual at the end of the phase 1 portion of the study as data from the phase I study suggest that an alternative approach for the phase 2 portion of the study be undertaken. A newly designed Phase II trial is being developed and will be submitted as a new study protocol.
- Being tested
- Tadalafil, Anti-MUC1 Vaccine, Anti-Influenza Vaccine, Tadalafil Placebo, Anti-MUC1 Vaccine Placebo
- Keywords
- HNSCC, Tadalafil, PDE5 Inhibition, Anti-MUC1 Vaccine, Recurrent Head and Neck Squamous Cell Carcinoma, Recurrent HNSCC, Second primary site disease stage III, Second primary site disease stage IV, Anti-Influenza Vaccine
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck, Head and Neck Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TadalafilDrug
Also called Cialis
Tadalafil tablets administered by mouth. Dose will be between 10 to 20 mg adjusted depending on patient's body weight. On course 1, Tadalafil will be administered daily for 19 consecutive days. On Course 2 through 4, Tadalafil will be administered daily for 14 consecutive days. No Tadalafil will be provided on Course 5.
Anti-MUC1 VaccineBiological
Also called Hiltonol
300 uL Anti-MUC1 vaccine will be administered intramuscularly in the right upper limb. Anti-MUC1 vaccine will be administer on Day 7 on course 1, on Day 10 for courses 2 through 4 and on Day 1 on course 5.
Anti-Influenza VaccineBiological
Also called Flublok
300 uL Anti-Influenza vaccine will be administered intramuscularly in the left upper limb. Anti-Influenza vaccine will be administer on Day 7 on course 1, on Day 10 for courses 2 through 4 and on Day 1 on course 5.
Tadalafil PlaceboOther
Placebo tablets mimicking Tadalafil administered by mouth. On course 1, Tadalafil Placebo will be administered daily for 19 consecutive days. On Course 2 through 4, Tadalafil placebo will be administered daily for 14 consecutive days. No Tadalafil Placebo will be provided on Course 5.
Anti-MUC1 Vaccine PlaceboOther
Placebo for Anti-MUC1 vaccine will be administered intramuscularly in the right upper limb. Placebo for Anti-MUC1 vaccine will be administer on Day 7 on course 1, on Day 10 for courses 2 through 4 and on Day 1 on course 5..
Standard of Care TreatmentOther
Treatment according to prescribed standard of care regimen.
Anti-Influenza Vaccine PlaceboOther
Placebo for Anti-Influenza vaccine will be administered intramuscularly in the left upper limb. Placebo for Anti-Influenza vaccine will be administer on Day 7 on course 1, on Day 10 for courses 2 through 4 and on Day 1 on course 5.
| Study group | Role | What they receive |
|---|---|---|
| Tadalafil plus Vaccine Group (Phase I) | Experimental | The first 6 participants will be enrolled in the open label Phase I portion of the study and will receive Tadalafil, Anti-mucin 1 (MUC1) Vaccine and the Anti-Influenza Vaccine for 5 courses. A standard of care (SOC) tumor removal surgery will be completed after the completion of Course 1. Course 2 will resume 5-8 weeks after completion of SOC tumor removal surgery. Receives: Drug: Tadalafil; Biological: Anti-MUC1 Vaccine; Biological: Anti-Influenza Vaccine |
| Tadalafil plus Vaccine Group (Phase II) | Experimental | After completion of the Phase I portion of the study, new participants will be enrolled for the randomized, placebo-controlled Phase II. Participants randomized in this group will receive Tadalafil, Anti-MUC1 Vaccine and the Anti-Influenza Vaccine for 5 courses. A standard of care (SOC) tumor removal surgery will be completed after the completion of Course 1. Course 2 will resume 5-8 weeks after completion of SOC tumor removal surgery. Receives: Drug: Tadalafil; Biological: Anti-MUC1 Vaccine; Biological: Anti-Influenza Vaccine |
| Tadalafil plus Vaccine Placebo Group (Phase II) | Experimental | After completion of the Phase I portion of the study, new participants will be enrolled for the randomized, placebo-controlled Phase II. Participants randomized in this group will receive Tadalafil, placebo for the Anti-MUC1 Vaccine and placebo for the Anti-Influenza Vaccine for 5 courses. A standard of care (SOC) tumor removal surgery will be completed after the completion of Course 1. Course 2 will resume 5-8 weeks after completion of SOC tumor removal surgery. Receives: Drug: Tadalafil; Other: Anti-MUC1 Vaccine Placebo; Other: Anti-Influenza Vaccine Placebo |
| Tadalafil Placebo plus Vaccine Group (Phase II) | Experimental | After completion of the Phase I portion of the study, new participants will be enrolled for the randomized, placebo-controlled Phase II. Participants randomized in this group will receive placebo for Tadalafil, the Anti-MUC1 Vaccine and the Anti-Influenza Vaccine for 5 courses. A standard of care (SOC) tumor removal surgery will be completed after the completion of Course 1. Course 2 will resume 5-8 weeks after completion of SOC tumor removal surgery. Receives: Biological: Anti-MUC1 Vaccine; Biological: Anti-Influenza Vaccine; Other: Tadalafil Placebo |
| Control Group | Other | For eligible participants who opt out of receiving study intervention. Participants in this group will receive SOC treatment only. Receives: Other: Standard of Care Treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1 - Number of participants experiencing adverse events and/or treatment limiting-toxicities after receiving protocol therapy.
The primary objective of the lead-in, open-label, single-arm, phase I part of study will evaluate the safety of Tadalafil in combination with anti-MUC1/anti-influenza vaccines (TV) in terms of adverse events (AEs), serious adverse events (SAEs) and treatment-limiting toxicities (TLTs).
Measured: Up to 2 Years
Phase 2 - Rate of tumor-specific immune response to protocol therapy.
The primary objective of phase II is to evaluate immune response (tumor-specific immune response of the anti- MUC1 and anti-influenza vaccines when combined with Tadalafil. Immune response will be evaluated by determining patients' immunological profile (e.g. peripheral blood mononuclear cells (PBMCs), leukocyte subsets, and serum cytokine levels) and immunological reactivity (e.g. through DTH skin test, T cell proliferation, by Enzyme-Linked ImmunoSpot (ELISPOT), specific Immunoglobulin G (IgG) concentration, and immune response by peripheral blood sera) before and after surgery, and during treatment with Tadalafil and the anti-MUC1 and anti-Influenza vaccines.
Measured: Up to 3.5 years
Secondary outcomes (2)
Phase 1 - Rate of tumor-specific immune response to protocol therapy.
Immune response will be evaluated by determining patients' immunological profile (e.g. peripheral blood mononuclear cells (PBMCs), leukocyte subsets, and serum cytokine levels) and immunological reactivity (e.g. through DTH skin test, T cell proliferation, by ELISPOT, specific IgG concentration, and immune response by peripheral blood sera) before and after surgery, and during treatment with Tadalafil and the anti-MUC1 and anti-Influenza vaccines.
Measured: Up to 2 years
Phase 1/2 - Rate of recurrence-free survival (RFS) in participants
The rate of recurrence-free survival (RFS) in patients with recurrent or second primary HNSCC after salvage surgery. RFS is defined as the time from date of Surgery to the date of first documented recurrence. All patients will be rendered disease free (i.e. no measurable disease) after surgery, thus any confirmed evidence of disease recurrence regardless of size or site will constitute the recurrence time point. Recurrence will be demonstrated by clinical assessments such as clinical examinations and tumor assessments (possibly) by CT, PET/CT or MRI.
Measured: Up to 3.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2015 (estimated)
- Study start25 Apr 2016
- Primary completion2 Jun 2019
- Study completion8 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Head and Neck Squamous Cell CarcinomaStudies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Donald T. Weed, MD, FACS
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Donald T. Weed, MD, FACS, University of Miami
- Investigators
- Donald T Weed, MD, FACS, Principal investigator, University of Miami
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02544880
- Sponsor's protocol ID
- 20140960
- Status last verified
- Jun 2021
- First submitted
- 4 Sep 2015
- Last updated
- 15 Jun 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Weed DT, Zilio S, Reis IM, Sargi Z, Abouyared M, Gomez-Fernandez CR, Civantos FJ, Rodriguez CP, Serafini P. The Reversal of Immune Exclusion Mediated by Tadalafil and an Anti-tumor Vaccine Also Induces PDL1 Upregulation in Recurrent Head and Neck Squamous Cell Carcinoma: Interim Analysis of a Phase I Clinical Trial. Front Immunol. 2019 May 31;10:1206. doi: 10.3389/fimmu.2019.01206. eCollection 2019.
PubMed 31214178
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PDE5 Inhibition Via Tadalafil (Cialis®) to Enhance Anti-Tumor MUC1 Vaccine Efficacy in Patients With Resectable, and Recurrent or Second Primary Head and Neck Squamous Cell Carcinoma (HNSCC): A Phase I/II Clinical Trial
- ClinicalTrials.gov ID
- NCT02544880
- Acronym / sponsor ID
- 20140960
- Keywords
- HNSCC, Tadalafil, PDE5 Inhibition, Anti-MUC1 Vaccine, Recurrent Head and Neck Squamous Cell Carcinoma, Recurrent HNSCC, Second primary site disease stage III, Second primary site disease stage IV
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Donald T. Weed, MD, FACSUniversity, hospital or other
- Study start
- 25 Apr 2016 (actual)
- Primary completion
- 2 Jun 2019 (actual)
- Study completion
- 8 Jun 2021 (actual)
- First posted
- 9 Sep 2015 (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.
The investigators hypothesize that Tadalafil treatment, by lowering Myeloid Derived Suppressor Cells (MDSCs) and regulatory T cells (Tregs), can prime an antitumor immune response and promote a permissive environment that should increase the efficacy of anti-tumor vaccine in a setting of minimal residual disease.
Detailed description
This study is halting accrual at the end of the phase 1 portion of the study as data from the phase I study suggest that an alternative approach for the phase 2 portion of the study be undertaken. A newly designed Phase II trial is being developed and will be submitted as a new study protocol.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Tadalafil plus Vaccine Group (Phase I) | Experimental | Drug: Tadalafil, Biological: Anti-MUC1 Vaccine, Biological: Anti-Influenza VaccineThe first 6 participants will be enrolled in the open label Phase I portion of the study and will receive Tadalafil, Anti-mucin 1 (MUC1) Vaccine and the Anti-Influenza Vaccine for 5 courses. A standard of care (SOC) tumor removal surgery will be completed after the completion of Course 1. Course 2 will resume 5-8 weeks after completion of SOC tumor removal surgery. |
| Tadalafil plus Vaccine Group (Phase II) | Experimental | Drug: Tadalafil, Biological: Anti-MUC1 Vaccine, Biological: Anti-Influenza VaccineAfter completion of the Phase I portion of the study, new participants will be enrolled for the randomized, placebo-controlled Phase II. Participants randomized in this group will receive Tadalafil, Anti-MUC1 Vaccine and the Anti-Influenza Vaccine for 5 courses. A standard of care (SOC) tumor removal surgery will be completed after the completion of Course 1. Course 2 will resume 5-8 weeks after completion of SOC tumor removal surgery. |
| Tadalafil plus Vaccine Placebo Group (Phase II) | Experimental | Drug: Tadalafil, Other: Anti-MUC1 Vaccine Placebo, Other: Anti-Influenza Vaccine PlaceboAfter completion of the Phase I portion of the study, new participants will be enrolled for the randomized, placebo-controlled Phase II. Participants randomized in this group will receive Tadalafil, placebo for the Anti-MUC1 Vaccine and placebo for the Anti-Influenza Vaccine for 5 courses. A standard of care (SOC) tumor removal surgery will be completed after the completion of Course 1. Course 2 will resume 5-8 weeks after completion of SOC tumor removal surgery. |
| Tadalafil Placebo plus Vaccine Group (Phase II) | Experimental | Biological: Anti-MUC1 Vaccine, Biological: Anti-Influenza Vaccine, Other: Tadalafil PlaceboAfter completion of the Phase I portion of the study, new participants will be enrolled for the randomized, placebo-controlled Phase II. Participants randomized in this group will receive placebo for Tadalafil, the Anti-MUC1 Vaccine and the Anti-Influenza Vaccine for 5 courses. A standard of care (SOC) tumor removal surgery will be completed after the completion of Course 1. Course 2 will resume 5-8 weeks after completion of SOC tumor removal surgery. |
| Control Group | Other | Other: Standard of Care TreatmentFor eligible participants who opt out of receiving study intervention. Participants in this group will receive SOC treatment only. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- Biopsy-proven recurrent or second primary HNSCC of the oral cavity, oropharynx, hypopharynx or larynx (second primary includes unknown primary)
- Stage III or IV (AJCC, 7th ed., 2010) recurrent or second primary HNSCC (For recurrent tumors, staging is determined by the recurrent stage, not by the original pretreatment stage.)
- Surgically resectable, recurrent or second primary HNSCC
- Prior radiation, with or without prior surgery and/or chemotherapy, to the head and neck for definitive treatment of HNSCC of the oral cavity, oropharynx, hypopharynx or larynx with previously documented complete clinical or radiographic response to initial treatment
- Age ≥ 18 years
Key exclusion criteria (33 listed)
- Salvage surgery is not recommended as per National Comprehensive Cancer Network (NCCN) guidelines, or after multidisciplinary treatment evaluation, including those with surgically unresectable disease at primary site or regional lymph nodes
- Recurrent or second primary AJCC Stage I or II HNSCC (for recurrent tumors, staging is determined by the recurrent stage, not by the original pretreatment stage).
- Distant metastatic disease
- Recurrent or second primary HNSCC of the nasopharynx, paranasal sinuses, or cervical esophagus
- Use of Phosphodiesterase Type 5 (PDE5) inhibitors such as vardenafil (Levitra®), Tadalafil (Cialis®), and sildenafil citrate (Viagra®) ≤15-days prior to (intended) enrollment
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 |
|---|---|---|
| TadalafilAlso: CialisTadalafil tablets administered by mouth. Dose will be between 10 to 20 mg adjusted depending on patient's body weight. On course 1, Tadalafil will be administered daily for 19 consecutive days. On Course 2 through 4, Tadalafil will be administered daily for 14 consecutive days. No Tadalafil will be provided on Course 5. | Drug | Tadalafil plus Vaccine Group (Phase I), Tadalafil plus Vaccine Group (Phase II), Tadalafil plus Vaccine Placebo Group (Phase II) |
| Anti-MUC1 VaccineAlso: Hiltonol300 uL Anti-MUC1 vaccine will be administered intramuscularly in the right upper limb. Anti-MUC1 vaccine will be administer on Day 7 on course 1, on Day 10 for courses 2 through 4 and on Day 1 on course 5. | Biological | Tadalafil Placebo plus Vaccine Group (Phase II), Tadalafil plus Vaccine Group (Phase I), Tadalafil plus Vaccine Group (Phase II) |
| Anti-Influenza VaccineAlso: Flublok300 uL Anti-Influenza vaccine will be administered intramuscularly in the left upper limb. Anti-Influenza vaccine will be administer on Day 7 on course 1, on Day 10 for courses 2 through 4 and on Day 1 on course 5. | Biological | Tadalafil Placebo plus Vaccine Group (Phase II), Tadalafil plus Vaccine Group (Phase I), Tadalafil plus Vaccine Group (Phase II) |
| Tadalafil PlaceboPlacebo tablets mimicking Tadalafil administered by mouth. On course 1, Tadalafil Placebo will be administered daily for 19 consecutive days. On Course 2 through 4, Tadalafil placebo will be administered daily for 14 consecutive days. No Tadalafil Placebo will be provided on Course 5. | Other | Tadalafil Placebo plus Vaccine Group (Phase II) |
| Anti-MUC1 Vaccine PlaceboPlacebo for Anti-MUC1 vaccine will be administered intramuscularly in the right upper limb. Placebo for Anti-MUC1 vaccine will be administer on Day 7 on course 1, on Day 10 for courses 2 through 4 and on Day 1 on course 5.. | Other | Tadalafil plus Vaccine Placebo Group (Phase II) |
| Standard of Care TreatmentTreatment according to prescribed standard of care regimen. | Other | Control Group |
| Anti-Influenza Vaccine PlaceboPlacebo for Anti-Influenza vaccine will be administered intramuscularly in the left upper limb. Placebo for Anti-Influenza vaccine will be administer on Day 7 on course 1, on Day 10 for courses 2 through 4 and on Day 1 on course 5. | Other | Tadalafil plus Vaccine Placebo Group (Phase II) |
Primary outcome
Phase 1 - Number of participants experiencing adverse events and/or treatment limiting-toxicities after receiving protocol therapy.
Time frame: Up to 2 Years
The primary objective of the lead-in, open-label, single-arm, phase I part of study will evaluate the safety of Tadalafil in combination with anti-MUC1/anti-influenza vaccines (TV) in terms of adverse events (AEs), serious adverse events (SAEs) and treatment-limiting toxicities (TLTs).
Phase 2 - Rate of tumor-specific immune response to protocol therapy.
Time frame: Up to 3.5 years
The primary objective of phase II is to evaluate immune response (tumor-specific immune response of the anti- MUC1 and anti-influenza vaccines when combined with Tadalafil. Immune response will be evaluated by determining patients' immunological profile (e.g. peripheral blood mononuclear cells (PBMCs), leukocyte subsets, and serum cytokine levels) and immunological reactivity (e.g. through DTH skin test, T cell proliferation, by Enzyme-Linked ImmunoSpot (ELISPOT), specific Immunoglobulin G (IgG) concentration, and immune response by peripheral blood sera) before and after surgery, and during treatment with Tadalafil and the anti-MUC1 and anti-Influenza vaccines.
2 secondary outcomes
Phase 1 - Rate of tumor-specific immune response to protocol therapy.
Time frame: Up to 2 years
Phase 1/2 - Rate of recurrence-free survival (RFS) in participants
Time frame: Up to 3.5 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2021.
- Results publication: PubMed 31214178Weed DT, Zilio S, Reis IM, Sargi Z, Abouyared M, Gomez-Fernandez CR, Civantos FJ, Rodriguez CP, Serafini P. The Reversal of Immune Exclusion Mediated by Tadalafil and an Anti-tumor Vaccine Also Induces PDL1 Upregulation in Recurrent Head and Neck Squamous Cell Carcinoma: Interim Analysis of a Phase I Clinical Trial. Front Immunol. 2019 May 31;10:1206. doi: 10.3389/fimmu.2019.01206. eCollection 2019.
- The Reversal of Immune Exclusion Mediated by Tadalafil and an Anti-tumor Vaccine Also Induces PDL1 Upregulation in Recurrent Head and Neck Squamous Cell Carcinoma: Interim Analysis of a Phase I Clinical TrialLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Donald T Weed, MD, FACS principal investigator
University of Miami
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Tadalafil, Anti-MUC1 Vaccine and Anti-Influenza Vaccine in people with Head and Neck Squamous Cell Carcinoma and Head and Neck Cancer, run by Donald T. Weed, MD, FACS at 1 site in United States.
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 26 inclusion and 33 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: finished, as of the sponsor's last update on 15 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1 - Number of participants experiencing adverse events and/or treatment limiting-toxicities after receiving protocol therapy. (time frame: Up to 2 Years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02544880, which also lists 1 linked publication.
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 15 Jun 2021.