Tadalafil in Treating Patients Undergoing Surgery for Cancer of the Oral Cavity or Oropharynx

A study testing Tadalafil in people with Head and Neck Cancer, run by Donald T. Weed at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

RATIONALE: Biological therapies, such as tadalafil, may stimulate the immune system in different ways and stop tumor cells from growing. PURPOSE: This randomized clinical trial is studying how well tadalafil works in treating patients who are undergoing surgery for cancer of the oral cavity or oropharynx. Read more about this study

Who is it for?: Ages 18 to 120 years
Conditions the study is for: Head and Neck Cancer
What is being tested?: Tadalafil
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 35 participants
Where: 1 siteUnited States
Study dates: Sep 2008to Apr 2015
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 to 120 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patients with surgically resectable oral cavity SCC, all subsites, T1 - T4, N0 - N3
Patients with surgically resectable oropharyngeal SCC, all subsites, T1 - T2, N0 - N1
Patients with surgically resectable T4 oropharyngeal SCC, all subsites, N0 - N3
Patients must be 18 years old or older

Who cannot join

Patients with previous surgical resection, radiation, or chemotherapy will be excluded to rule out possible effects of local tissue changes secondary to previous treatment
Patients with surgically unresectable disease at primary site or regional lymph nodes
Patients with T1 - T2 SCC oropharynx, N2 - N3
Patients with T3 SCC oropharynx , N0 - N3
Any patient for whom non-surgical therapy is recommended as treatment of choice after multidisciplinary treatment evaluation
Patients with an altered mental status or not capacitated for their medical decision making

Show all 24Show fewer

Patients with severe or unstable cardiac or cerebrovascular disease are excluded
myocardial infarction within the last 90 days
unstable angina or angina occurring during sexual intercourse
New York Heart Association Class 2 or greater heart failure in the last 6 months
uncontrolled arrhythmias
hypotension (<90/50 mm Hg), or uncontrolled hypertension (>170/100 mm Hg)
stroke within the last 6 months
Left ventricle outflow obstruction.
Pregnant and nursing mothers will not be enrolled given unknown effects to offspring
Concurrent nitrate, alpha-blocker, or cytochrome P-450 inhibitor use
Renal Insufficiency defined as creatinine clearance less than 51.
Creatinine clearance will be determined by the following Cockcroft-Gault Equation: (140-age) * (Wt in kg) * (0.85 if female) / (72 * Cr)
Patients with hepatic insufficiency.
Patients currently taking a Phosphodiesterase (PDE) inhibitors for erectile dysfunction
Patients who are immunocompromised, for reasons not directly related to patients malignancy
Patients with significant alcohol or drug abuse
Patients with unilateral blindness, hereditary retinal disorders, or increased risk of blindness
Patients with unilateral deafness, history of hearing loss, hearing aid dependence, or clinically evident hearing loss

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Miami Sylvester Comprehensive Cancer Center - Miami
Miami, Florida, 33136

Other trials in United States

About this study

Official title: Pilot Study of Phosphodiesterase-5 Inhibitor Tadalafil (Cialis) as an Immunomodulator in Patients With Oral Cavity and Oropharyngeal Squamous Cell Carcinoma.

RATIONALE: Biological therapies, such as tadalafil, may stimulate the immune system in different ways and stop tumor cells from growing.

PURPOSE: This randomized clinical trial is studying how well tadalafil works in treating patients who are undergoing surgery for cancer of the oral cavity or oropharynx.

Read the detailed description

OBJECTIVES:

To analyze the phenotype and the function of the tumor-induced suppressive network associated with squamous cell carcinoma (SCC) of the head and neck in patients with SCC of the oral cavity or oropharynx treated with tadalafil followed by definitive surgical resection.
To analyze the immune response before and after treatment with tadalafil to determine whether or not tadalafil treatment modulates in these patients.
To compare two doses of tadalafil to determine whether there are measurable differences in immune response in these patients.
To analyze treatment-related side effects of tadalafil at each of the two doses tested in these patients.

OUTLINE: Patients are randomized to 1 of 3 treatment arms.

Arm I: Patients receive oral tadalafil once daily on days 1-20 in the absence of unacceptable toxicity.
Arm II: Patients receive oral tadalafil (at a higher dose than in arm I) once daily on days 1-20 in the absence of unacceptable toxicity.
Arm III: Patients receive oral placebo once daily on days 1-20 in the absence of unacceptable toxicity.

All patients undergo scheduled definitive surgical resection on day 23.

Patients undergo blood sample collection at baseline, on day 20, and at 6 weeks after surgical resection for correlative laboratory studies. Patients also undergo tumor tissue sample collection at baseline and at the time of surgical resection. Samples are analyzed for immunological markers by Fluorescence-activated cell sorting (FACS) and Immunohistochemistry (IHC).

After completion of study treatment, patients are followed periodically for at least 3 years.

Conditions: Head and Neck Cancer
Being tested: Tadalafil, Placebo
Keywords: stage I squamous cell carcinoma of the lip and oral cavity, stage I squamous cell carcinoma of the oropharynx, stage II squamous cell carcinoma of the lip and oral cavity, stage II squamous cell carcinoma of the oropharynx, stage III squamous cell carcinoma of the oropharynx, stage III squamous cell carcinoma of the lip and oral cavity, stage IV squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the lip and oral cavity, stage I verrucous carcinoma of the oral cavity, stage II verrucous carcinoma of the oral cavity, stage III verrucous carcinoma of the oral cavity, stage IV verrucous carcinoma of the oral cavity
Medical subject headings: Head and Neck Neoplasms, Squamous Cell Carcinoma of Head and Neck

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TadalafilDrug
Also called Cialis
Given orally
PlaceboOther
Given orally

Study groups in NCT00843635
Study group	Role	What they receive
Arm A - Tadalafil 10mg	Experimental	Patients will receive 10mg/day Tadalafil orally on days 1 - 20 in the absence of unacceptable toxicity. Receives: Drug: Tadalafil
Arm B - Tadalafil 20mg	Experimental	Patients will receive 20mg/day Tadalafil orally on days 1 - 20 in the absence of unacceptable toxicity. Receives: Drug: Tadalafil
Arm C - Placebo	Placebo comparator	Patients receive oral placebo once daily on days 1-20 in the absence of unacceptable toxicity. Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Ratio of MDSC Concentration in the Blood
Ratio of the number of Myeloid Derived Suppressor Cells (MDSC) in the Blood, per treatment group, from Baseline to End of Treatment at Time of Surgery.
Measured: Baseline, End of Treatment at time of Surgery
Ratio of T-reg Cell Concentration in the Blood
Ratio of the number of regulatory T cells in the blood, per treatment group, from Baseline to End of Treatment at Time of Surgery..
Measured: Baseline, End of Treatment at Time of Surgery
Ratio of Tumor-specific T-cell Concentration in the Blood
Ratio of the number of tumor specific T cells in the blood, per treatment group, from Baseline to End of Treatment at Time of Surgery.
Measured: Baseline, End of Treatment at Time of Surgery

Secondary outcomes (2)

Optimal Dosing Schedule for Tadalafil
Measured: Baseline, End of Treatment at Time of Surgery.
Number of Participants Experiencing Adverse Events
Assessment of Treatment-related Side Effects. Number of participants experiencing adverse events
Measured: From Day 1 to Day 20

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2008Apr 2015

First posted13 Feb 2009 (estimated)
Study startSep 2008
Primary completionApr 2015
Study completionApr 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Head and Neck CancerStudies 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 N/A
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 35 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00843635
Sponsor's protocol ID: 20070918
Other IDs: SCCC-2008006
Status last verified: Sep 2015
First submitted: 12 Feb 2009
Last updated: 19 Oct 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Weed DT, Vella JL, Reis IM, De la Fuente AC, Gomez C, Sargi Z, Nazarian R, Califano J, Borrello I, Serafini P. Tadalafil reduces myeloid-derived suppressor cells and regulatory T cells and promotes tumor immunity in patients with head and neck squamous cell carcinoma. Clin Cancer Res. 2015 Jan 1;21(1):39-48. doi: 10.1158/1078-0432.CCR-14-1711. Epub 2014 Oct 15.
PubMed 25320361

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
Proton Re-irradiation in Patients With Recurrent or Second Primary Head and Neck Cancer , a Multicentre Phase II Single Arm Trial
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RecruitingPhase 2/3
Multicenter Validation Trial of [18F]AlF-FAPI-74 for PET Imaging of Cancer-associated Fibroblasts Through Fibroblast Activation Protein Inhibitors (FAPI) in Different Tumor Types
Oesophageal Cancer, Gastric Cancer
RecruitingPhase 2
Proton Spatially Fractionated Radiotherapy or Photon Stereotactic Body Radiotherapy in Combination With Pembrolizumab Before Surgery for the Treatment of Locally Advanced and Radiation-Naive Locoregionally Recurrent Oral Cavity Cancer, OSPRI Trial
Locally Advanced Oral Cavity Squamous Cell Carcinoma, Locally Recurrent Oral Cavity Squamous Cell Carcinoma
RecruitingPhase 4
Lidocaine Infiltration and Neuroimmunomodulation in Head and Neck Cancer Surgery
Head and Neck Cancer (H&N)

All Head and Neck Cancer trials

Study at a glance

From the registry record, last updated by the sponsor on 19 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Pilot Study of Phosphodiesterase-5 Inhibitor Tadalafil (Cialis) as an Immunomodulator in Patients With Oral Cavity and Oropharyngeal Squamous Cell Carcinoma.
ClinicalTrials.gov ID: NCT00843635
Acronym / sponsor ID: 20070918
Conditions: Head and Neck Cancer
Keywords: stage I squamous cell carcinoma of the lip and oral cavity, stage I squamous cell carcinoma of the oropharynx, stage II squamous cell carcinoma of the lip and oral cavity, stage II squamous cell carcinoma of the oropharynx, stage III squamous cell carcinoma of the oropharynx, stage III squamous cell carcinoma of the lip and oral cavity, stage IV squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the lip and oral cavity
Study type: Interventional
Recruitment status: Completed
Enrolment: 35 participants (actual)
Lead sponsor: Donald T. WeedUniversity, hospital or other
Study start: Sep 2008
Primary completion: Apr 2015 (actual)
Study completion: Apr 2015 (actual)
First posted: 13 Feb 2009 (estimated)
Results: Posted 13 Aug 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

RATIONALE: Biological therapies, such as tadalafil, may stimulate the immune system in different ways and stop tumor cells from growing.

PURPOSE: This randomized clinical trial is studying how well tadalafil works in treating patients who are undergoing surgery for cancer of the oral cavity or oropharynx.

Detailed description

OBJECTIVES:

To analyze the phenotype and the function of the tumor-induced suppressive network associated with squamous cell carcinoma (SCC) of the head and neck in patients with SCC of the oral cavity or oropharynx treated with tadalafil followed by definitive surgical resection.
To analyze the immune response before and after treatment with tadalafil to determine whether or not tadalafil treatment modulates in these patients.
To compare two doses of tadalafil to determine whether there are measurable differences in immune response in these patients.
To analyze treatment-related side effects of tadalafil at each of the two doses tested in these patients.

OUTLINE: Patients are randomized to 1 of 3 treatment arms.

Arm I: Patients receive oral tadalafil once daily on days 1-20 in the absence of unacceptable toxicity.
Arm II: Patients receive oral tadalafil (at a higher dose than in arm I) once daily on days 1-20 in the absence of unacceptable toxicity.
Arm III: Patients receive oral placebo once daily on days 1-20 in the absence of unacceptable toxicity.

All patients undergo scheduled definitive surgical resection on day 23.

After completion of study treatment, patients are followed periodically for at least 3 years.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 3

Arm	Type	Receives
Arm A - Tadalafil 10mg	Experimental	Drug: TadalafilPatients will receive 10mg/day Tadalafil orally on days 1 - 20 in the absence of unacceptable toxicity.
Arm B - Tadalafil 20mg	Experimental	Drug: TadalafilPatients will receive 20mg/day Tadalafil orally on days 1 - 20 in the absence of unacceptable toxicity.
Arm C - Placebo	Placebo comparator	Other: PlaceboPatients receive oral placebo once daily on days 1-20 in the absence of unacceptable toxicity.

Who may qualify

Ages: 18 to 120 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

Patients with surgically resectable oral cavity SCC, all subsites, T1 - T4, N0 - N3
Patients with surgically resectable oropharyngeal SCC, all subsites, T1 - T2, N0 - N1
Patients with surgically resectable T4 oropharyngeal SCC, all subsites, N0 - N3
Patients must be 18 years old or older

Key exclusion criteria (24 listed)

Patients with previous surgical resection, radiation, or chemotherapy will be excluded to rule out possible effects of local tissue changes secondary to previous treatment
Patients with surgically unresectable disease at primary site or regional lymph nodes
Patients with T1 - T2 SCC oropharynx, N2 - N3
Patients with T3 SCC oropharynx , N0 - N3
Any patient for whom non-surgical therapy is recommended as treatment of choice after multidisciplinary treatment evaluation

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: CialisGiven orally	Drug	Arm A - Tadalafil 10mg, Arm B - Tadalafil 20mg
PlaceboGiven orally	Other	Arm C - Placebo

Primary outcome

Ratio of MDSC Concentration in the Blood
Time frame: Baseline, End of Treatment at time of Surgery
Ratio of the number of Myeloid Derived Suppressor Cells (MDSC) in the Blood, per treatment group, from Baseline to End of Treatment at Time of Surgery.
Ratio of T-reg Cell Concentration in the Blood
Time frame: Baseline, End of Treatment at Time of Surgery
Ratio of the number of regulatory T cells in the blood, per treatment group, from Baseline to End of Treatment at Time of Surgery..
Ratio of Tumor-specific T-cell Concentration in the Blood
Time frame: Baseline, End of Treatment at Time of Surgery
Ratio of the number of tumor specific T cells in the blood, per treatment group, from Baseline to End of Treatment at Time of Surgery.

2 secondary outcomes

Optimal Dosing Schedule for Tadalafil
Time frame: Baseline, End of Treatment at Time of Surgery.
Number of Participants Experiencing Adverse Events
Time frame: From Day 1 to Day 20

Results and safety

Results posted to the registry on 13 Aug 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Arm A - Tadalafil 10mg	15	13
Arm B - Tadalafil 20mg	15	13
Arm C - Placebo	5	5

Primary outcome: Ratio of MDSC Concentration in the Blood

Time frame: Baseline, End of Treatment at time of Surgery. Median (Inter-Quartile Range). Unit: ratio from baseline

Measure	Arm A - Tadalafil 10mg n = 13	Arm B - Tadalafil 20mg n = 13	Arm C - Placebo n = 5
Value	0.7680 (0.6440 to 1.010)	0.7919 (0.4344 to 1.115)	0.9876 (0.8478 to 1.026)

Primary outcome: Ratio of T-reg Cell Concentration in the Blood

Time frame: Baseline, End of Treatment at Time of Surgery. Median (Inter-Quartile Range). Unit: ratio from baseline

Measure	Arm A - Tadalafil 10mg n = 13	Arm B - Tadalafil 20mg n = 13	Arm C - Placebo n = 5
Value	0.7776 (0.5751 to 0.8869)	0.6789 (0.5234 to 1.033)	0.8421 (0.5255 to 0.9142)

Primary outcome: Ratio of Tumor-specific T-cell Concentration in the Blood

Time frame: Baseline, End of Treatment at Time of Surgery. Median (Inter-Quartile Range). Unit: ratio from baseline

Measure	Arm A - Tadalafil 10mg n = 12	Arm B - Tadalafil 20mg n = 10	Arm C - Placebo n = 3
Value	1.7401 (1.1478 to 2.7495)	1.9020 (1.0413 to 6.1008)	1.0933 (0.7884 to 1.2466)

Population analysed: Data for 31 patients were analyzed.

2 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Arm A - Tadalafil 10mg	1 of 15 (6.7%)	3 of 15 (20%)	Not reported
Arm B - Tadalafil 20mg	2 of 15 (13.3%)	8 of 15 (53.3%)	Not reported
Arm C - Placebo	0 of 5 (0%)	3 of 5 (60%)	Not reported

Limitations and caveats (from the sponsor): Race/Ethnicity baseline characteristics reported for 34 of 35 patients enrolled. Data analyzed for outcome measure for the 31 participants who completed the study.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 25320361Weed DT, Vella JL, Reis IM, De la Fuente AC, Gomez C, Sargi Z, Nazarian R, Califano J, Borrello I, Serafini P. Tadalafil reduces myeloid-derived suppressor cells and regulatory T cells and promotes tumor immunity in patients with head and neck squamous cell carcinoma. Clin Cancer Res. 2015 Jan 1;21(1):39-48. doi: 10.1158/1078-0432.CCR-14-1711. Epub 2014 Oct 15.

Related trials for Head and Neck Cancer

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
Proton Re-irradiation in Patients With Recurrent or Second Primary Head and Neck Cancer , a Multicentre Phase II Single Arm Trial
Head & Neck Cancer
RecruitingPhase 2/3
Multicenter Validation Trial of [18F]AlF-FAPI-74 for PET Imaging of Cancer-associated Fibroblasts Through Fibroblast Activation Protein Inhibitors (FAPI) in Different Tumor Types
Oesophageal Cancer, Gastric Cancer
RecruitingPhase 2
Proton Spatially Fractionated Radiotherapy or Photon Stereotactic Body Radiotherapy in Combination With Pembrolizumab Before Surgery for the Treatment of Locally Advanced and Radiation-Naive Locoregionally Recurrent Oral Cavity Cancer, OSPRI Trial
Locally Advanced Oral Cavity Squamous Cell Carcinoma, Locally Recurrent Oral Cavity Squamous Cell Carcinoma
RecruitingPhase 4
Lidocaine Infiltration and Neuroimmunomodulation in Head and Neck Cancer Surgery
Head and Neck Cancer (H&N)

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 principal investigator

University of Miami Sylvester Comprehensive Cancer Center

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Tadalafil in people with Head and Neck Cancer, run by Donald T. Weed 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 4 inclusion and 24 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 19 Oct 2015. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Aug 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Ratio of MDSC Concentration in the Blood (time frame: Baseline, End of Treatment at time of Surgery). The study lists 3 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 NCT00843635, 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 19 Oct 2015.