Chemoradiotherapy-Induced Severe Oral MucositisPhase 2/3VOICENCT04648020
Clonidine HCl MBT vs. Placebo to Prevent Chemoradiotherapy-Induced Severe Oral Mucositis in Oropharyngeal Cancer.
A Phase 2/3 study testing Clonidine HCl Mucoadhesive Buccal Tablet in people with Chemoradiotherapy-Induced Severe Oral Mucositis, run by Monopar Therapeutics at 74 sites in 5 countries.
Trial summary
This study is being performed to evaluate the effectiveness of a new drug, clonidine HCl MBT, to prevent the onset of severe oral mucositis (SOM) in patients with oropharyngeal cancer (OPC) who are being treated with chemoradiotherapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chemoradiotherapy-Induced Severe Oral Mucositis
- What is being tested?
- Clonidine HCl Mucoadhesive Buccal Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 190 participants
- Where
- 74 sitesin 5 countries
- Study dates
- 11 Feb 2021to 14 May 2023
- Phase
- Phase 2/3
- 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
- Male/Female patients of ≥ 18 years of age. Patients with histologically or pathologically confirmed squamous cell carcinoma of the oropharynx (including tonsils or the base of tongue) at one or several sites.
- Patients treated with surgical resection of their primary tumor for localized or locally advanced disease T ≥ T0 and/or N ≥ N1 without distant metastasis (M0) (American Joint Committee on Cancer - AJCC 8th edition) and initiating adjuvant concurrent CRT within 8 weeks post-operatively. Unknown primary with node-positive disease confirmed to be Squamous Cell Carcinoma would be allowed or Patients who will be treated with definitive concurrent CRT for locally advanced disease T ≥ T0 and/or N ≥ N1 M0 (American Joint Committee on Cancer - AJCC 8th edition).
- Patients eligible to receive a continuous course of external fractionated irradiation [conventional or intensity modulated radiation therapy (IMRT)] based on a daily dosing of 1.8 to 2.2 Gy/day 5 days/week in combination with cisplatin monotherapy either every 3 weeks (100 mg/m2) or weekly cisplatin (40 mg/m2). Alternative treatment regimens are allowed only if cisplatin is contraindicated. The decision on which cisplatin regimen to use in combination with IMRT and study drug/placebo will be at the discretion of the investigator.
- Radiation plan must include delivery of a cumulative dose of 60-72 Gy. The oropharynx should receive at least 50 Gy.
- Patients with adequate laboratory values defined as:
- Absolute neutrophil count ≥ 1.5 × 10^9/L
Show all 17Show fewer
- Platelet count ≥ 75 × 10^9/L
- Hemoglobin ≥ 9 g/dL
- Creatinine blood level ≤ 1.5 × upper limit of the normal range (ULN)
- Total bilirubin ≤ 1.5 × ULN; patients with Gilbert's Syndrome can be included if hyperbilirubinemia ≤ 3 × ULN
- Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × ULN
- Patients with Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. A performance status of 2 is allowed only if due to a patient's malignancy.
- Patients must provide written informed consent.
- Human Papillomavirus (HPV) status documented by immunohistochemical detection of p16 expression in the tumor.
- Negative serum pregnancy test for females of child-bearing potential at screening. A female is eligible to enter and participate in the study if the female is of non-child-bearing potential (i.e., physiologically incapable of becoming pregnant), including any female who has had a hysterectomy, a bilateral oophorectomy (ovariectomy), a bilateral tubal ligation, or is post-menopausal with a minimum of 1 year without menses.
- Males with female partners of child-bearing potential and females of child-bearing potential must agree to use effective contraception starting prior to the first day of study drug treatment and continuing for 3 months after the last dose of study drug MBT.
- Patients must be willing to complete questionnaires on a tablet, home computer, or paper form.
Who cannot join
- Patients with no tumor or lesion in the oropharynx.
- Prior induction chemotherapy for treatment of current malignancy.
- Patients with planned accelerated IMRT.
- Evidence of a concomitant other malignancy and/or any prior malignancy without complete remission in the last 2 years, except adequately treated basal or squamous cell carcinoma of the skin or in situ cervical cancer.
- Patients with OM at baseline, any other oral ulceration or active oral infection (e.g., aphthous ulcers, orofacial herpes). Patients with post-operative pain of the mouth or throat are eligible.
- Patients with known human immunodeficiency virus (HIV) seropositivity, known active Hepatitis B or C or known active tuberculosis.
Show all 22Show fewer
- Patients with systolic blood pressure (BP) < 100 mmHg and/or diastolic BP < 50 mmHg.
- Patients with symptomatic cardiac dysrhythmia.
- Patients with recent (less than 6 months) acute cardiovascular diseases (i.e., stroke, myocardial infarction).
- Patients with any clinical condition, psychiatric condition, or prior therapy that, in the opinion of the investigator, would make the patient unsuitable for the study or unable to comply with study requirements and follow-up visits.
- Patients currently being treated with sultopride, clonidine hydrochloride (eg, Catapres®), pentoxifylline or pilocarpine.
- Patients intended to be treated specifically to prevent OM with any of the following:
- Bioadherent agents and mouthwashes: i. GelClair (consists of polyvinylpyrrolidone, hyaluronic acid, and glycyrrhetinic acid) ii. Sucralfate iii. Episil mouth spray iv. MuGard oral mucoadhesive v. Saforis (L-glutamine (topical)) b. Drug therapies and biologics: i. Amifostine (and similar free radical scavenger/antioxidant medications) ii. Palifermin (recombinant human keratinocyte growth factor-(KGF-1)) iii. Glutamine b. Interventional therapies i. Low level laser therapy (LLLT)
- Patients who are unable to tolerate oral diet and/or are feeding tube dependent at baseline.
- Patients receiving an approved or an investigational anti-cancer agent other than those specified in this study.
- Patients with a known hypersensitivity to clonidine or any of the MBT excipients.
- Women who are pregnant or breast-feeding.
- Patients whose medical, psychological or surgical conditions are unstable and may affect the study completion and/or compliance and/or the ability to give informed consent.
- Men and women of child-bearing age and their respective partners unwilling to use a highly effective contraception method during the study and for 3 months after the last administration of study drug.
- Patient who has participated in another clinical trial with an investigational drug in the last 30 days prior to randomization in the present clinical study.
- Subjects with orthostatic hypotension, defined by a decrease of systolic BP and/or diastolic BP above 20 mmHg when the patient stands up.
- Conditions including but not limited to COVID-19 which would confound the assessment of the effects and/or safety of study medication in the opinion of the investigator.
Trial locations and contacts
74 sites in 5 countries.
74 sites in 5 countries
United States48 sites
Hendrick Cancer Center
Abilene, Texas, 79601
Summa Health System
Akron, Ohio, 44304
University Cancer & Blood Center
Athens, Georgia, 30607
Greater Baltimore Medical Center
Baltimore, Maryland, 21204
PeaceHealth
Bellingham, Washington, 98225
Boca Raton Regional Hospital
Boca Raton, Florida, 33486
UnityPoint Health
Cedar Rapids, Iowa, 52403
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27514
Charleston Oncology
Charleston, South Carolina, 29406
Novant Health Cancer Institute
Charlotte, North Carolina, 28204
University of Cincinnati Medical Center
Cincinnati, Ohio, 45219
IACT Health (Centricity Research)
Columbus, Georgia, 31904
Decatur Memorial Hospital
Decatur, Illinois, 62526
Des Moines Oncology Research Association
Des Moines, Iowa, 50309
Henry Ford Health System
Detroit, Michigan, 48202
Edward Elmhurst Health
Elmhurst, Illinois, 60126
NorthShore University Health Systems
Evanston, Illinois, 60201
Providence Regional Cancer Partnership
Everett, Washington, 98201
Summit Health
Florham Park, New Jersey, 07932
Orange Coast Memorial Medical Center
Fountain Valley, California, 92708
CaroMont Regional Medical Center
Gastonia, North Carolina, 28054
Grand Valley Oncology
Grand Junction, Colorado, 81505
HSHS St. Vincent Hospital Cancer Centers at HSHS St. Vincent Hospital
Green Bay, Wisconsin, 54301
AMITA Health
Hinsdale, Illinois, 60521
Ballad Health
Johnson City, Tennessee, 37604
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
Long Beach Memorial Medical Center
Long Beach, California, 90806
East Jefferson General Hospital
Metairie, Louisiana, 70006
Miami Cancer Institute
Miami, Florida, 33176
New York Cancer and Blood Specialists
New York, New York, 10028
Northwell Health
New York, New York, 11042
Christiana Care Health Services
Newark, Delaware, 19713
Eastern Virginia Medical School
Norfolk, Virginia, 23507
Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104
Memorial Healthcare System
Pembroke Pines, Florida, 33028
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
AHN Cancer Institute - Allegheny General
Pittsburgh, Pennsylvania, 15212
Mary Hillman Radiation Oncology Center at UPMC Shadyside
Pittsburgh, Pennsylvania, 15232
Pomona Valley Hospital Medical Center
Pomona, California, 91767
Rhode Island Hospital
Providence, Rhode Island, 02903
Benaroya Research Institute at Virginia Mason
Seattle, Washington, 98101
Louisiana State University Health - Shreveport
Shreveport, Louisiana, 71103
Willis-Knighton Cancer Center
Shreveport, Louisiana, 71103
Cox Medical Centers
Springfield, Missouri, 65807
Oklahoma Cancer Specialists
Tulsa, Oklahoma, 74146
Reading Hospital
West Reading, Pennsylvania, 19611
Novant Health Cancer Institute - Forsyth
Winston-Salem, North Carolina, 27103
Mercy Health
Youngstown, Ohio, 44501
France11 sites
Centre Hospitalier Universitaire Amiens-Picardie
Amiens, 80054
Centre Hospitalier Universitaire Morvan / Centre Hospitalier Universitaire de Brest
Brest, 29609
Institut Andree Dutreix / Centre de Cancerologie Dunkerque
Coudekerque-Branche, Dunkerque, 59210
Centre hopitalier intercommunal de Créteil
Créteil, 94000
Centre Hospitalier de Dax-Côte d'Argent
Dax, 40100
Clinique François Chénieux
Limoges, 87039
Hôpital Saint Joseph
Marseille, 13008
Centre Hospitalier Universitaire La miletrie
Nice, 06000
Institut Jean Godinot
Reims, 51100
CHU de Saint Etienne
Saint-Priest-en-Jarez, 42270
Institut Gustave Roussy, Desmoulins
Villejuif, 94800
Spain11 sites
Hospital Universitario Cruces de Bilbao
Barakaldo, Bizkaia, 48903
Hospital Universitari Vall d'Hebron
Barcelona, 08035
Institut Català d'Oncologia Hospitalet (Hospital Duran i Reynals)
Barcelona, 08908
Hospital Universitario Quirónsalud Madrid
Madrid, 28223
Hospital Universitario Puerta de Hierro Majadahonda
Majadahonda, 28222
Hospital Universitari Son Espases
Palma, Balearic Islands, 07120
Hospital Universitari Son Llàtzer
Palma de Mallorca, 07098
Hospital Complejo Universitario de Navarra
Pamplona, 31008
Hospital de Donostia
San Sebastián, 20014
Hospital Clínico Universitario Santiago de Compostela
Santiago de Compostela, 15706
Hospital Meixoeiro
Vigo, Pontevedra, 36214
Germany3 sites
Universitatsklinikum Freiburg
Freiburg im Breisgau, 79106
Klinikum Kassel GmbH
Kassel, 34125
Caritas Klinikum Saarbrucken St. Theresia
Saarbrücken, 66113
About this study
Official title: A Phase 2b/3, Multicenter, Randomized, Double-blind, Placebo-controlled Study Comparing the Efficacy and Safety of Clonidine Mucoadhesive Buccal Tablet to Placebo to Prevent Chemoradiotherapy-induced Severe Oral Mucositis in Patients With Oropharyngeal Cancer
This study is being performed to evaluate the effectiveness of a new drug, clonidine HCl MBT, to prevent the onset of severe oral mucositis (SOM) in patients with oropharyngeal cancer (OPC) who are being treated with chemoradiotherapy. OPC occurs on the back of the tongue or throat and is often treated by the use of chemoradiotherapy, where radiation is localized to these areas. Radiation to the OPC affected tissues causes the release of small proteins called cytokines that cause damage to the area surrounding the tumor including the oral cavity. This damage is characterized by the formation of mucositis which includes redness, pain and ulcers in the mouth and back of the throat. In addition, as more chemoradiation is administered to treat OPC, the inability to eat a solid diet (a Grade 3 mucositis) or to consume anything at all by mouth (a Grade 4 mucositis) occurs in many patients. Collectively, Grade 3 and Grade 4 mucositis is referred to as SOM. It is a frequent, debilitating side effect of chemoradiation in OPC that may cause patients to stop or interrupt their treatment, develop other side effects like the inability to swallow, or require the increased use of pain medications. OPC survivors who have successful treatment of their tumors often develop permanent swallowing, speaking and range of motion issues that may be linked back to the inability to eat and/or drink caused by SOM during their chemoradiotherapy treatment. Clonidine may inhibit the production of cytokines that cause SOM and clonidine HCl mucoadhesive buccal tablet (MBT) has been designed to deliver sustained high levels of clonidine in the oral cavity, potentially decreasing cytokine production and leading to a decrease in the incidence of SOM. Clonidine HCl MBT is a once per day treatment provided as a tablet that a patient may self-administer to the gums, where it sticks tightly to release clonidine over many hours. The primary objective of this Phase 2b/3 study is to evaluate whether clonidine HCl MBT is more effective than placebo MBT in decreasing the incidence of SOM.
Read the detailed description
This is a sequential design Phase 2b/3 multicenter, randomized (1:1), double-blind, placebo-controlled, parallel group study to compare the efficacy and safety of clonidine HCl MBT to placebo MBT in the prevention of severe oral mucositis (SOM) in patients with oropharyngeal cancer (OPC) undergoing chemoradiotherapy (CRT). Best supportive care (BSC) will be allowed as per individual institutional practice with some exceptions as described in the inclusion and exclusion criteria. Eligible patients will be randomized to receive either clonidine MBT or placebo. Patients will be centrally randomized in a 1:1 ratio. The randomization will be stratified by p16 status (positive or negative). Randomized patients will be required to self-apply the study drug to the gum once a day in addition to BSC. The first application of MBT study drug will be performed on Day 1 of the CRT regimen. Each site will require the patient to follow the same local practice for BSC per Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) guidelines with some exceptions as described in the inclusion and exclusion criteria. Daily, self-administered MBT study drug will be continued once daily for the entire duration of CRT treatment; defined as from Day 1 of CRT until the last day of CRT (anticipated to be approximately 4-8 weeks depending on the patient's prescribed CRT plan). Patients will be recruited sequentially into either the Phase 2b or the Phase 3 part of the study. An interim analysis will be conducted when Phase 2b patients have either completed their CRT or discontinued from the study. The Data Monitoring Committee (DMC) will review the Phase 2b efficacy and safety data at the interim analysis and will make a recommendation on proceeding with the Phase 3 part of the study.
- Being tested
- Clonidine HCl Mucoadhesive Buccal Tablet, Placebo Mucoadhesive Buccal Tablet
- Keywords
- Mucositis, Oropharyngeal Cancer, Clonidine, Chemoradiotherapy, Severe Oral Mucositis, Monopar, Oral Mucositis, Head and Neck Cancer, Oral Cavity, Oropharynx, Mouth Sores
- Medical subject headings
- Mucositis, Oropharyngeal Neoplasms, Stomatitis, Head and Neck Neoplasms, Oral Ulcer
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Clonidine HCl Mucoadhesive Buccal TabletDrug
Also called Validive®
100 μg of clonidine per tablet
Placebo Mucoadhesive Buccal TabletDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo Mucoadhesive Buccal Tablet given daily during chemoradiotherapy Receives: Drug: Placebo Mucoadhesive Buccal Tablet |
| Clonidine HCl Mucoadhesive Buccal Tablet (MBT) | Experimental | Clonidine HCl MBT given daily during chemoradiotherapy Receives: Drug: Clonidine HCl Mucoadhesive Buccal Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
To demonstrate the efficacy of HCl MBT to prevent SOM in OPC patients receiving CRT.
The occurrence of SOM (Yes/No), defined as any reporting of World Health Organization (WHO) Grade 3-4 OM, from the first day to the last day of CRT. The WHO mucositis grading scale will be used to assess the occurrence of SOM in this trial. The WHO grading scale grades OM from 0 to 4 according to severity of clinical observation and functional limitation, with Grade 4 = oral alimentation impossible, Grade 3 = Oral ulcers, liquid diet only, Grade 2 = Oral erythema, ulcers, solid diet tolerated, Grade 1 = Oral soreness, erythema, and Grade 0 = normal, no mucositis (no signs, no symptoms).
Measured: From the first CRT treatment through the end of the study treatment period, which is estimated to be 7 weeks.
Secondary outcomes (1)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Evaluate the safety and tolerability of administering HCl MBT to OPC patients receiving CRT by assessing the number and severity of treatment-emergent adverse events (TEAE) and specifically those TEAEs of special interest. Adverse events are graded and tabulated using NCI CTCAE v5.0.
Measured: Up to 1 year after the first dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2020
- Study start11 Feb 2021
- Primary completion14 May 2023
- Study completion14 May 2023
Why it stopped: Interim Analysis did not meet the pre-defined threshold for efficacy of a 15% absolute difference in SOM prevention between Validive and placebo.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chemoradiotherapy-Induced Severe Oral MucositisStudies 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 2/3
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 190 participants (actual)
Sponsor and investigators
- Lead sponsor
- Monopar Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Holli Carlson, Study director, Monopar Therapeutics Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04648020
- Sponsor's protocol ID
- MNPR-301-001
- Acronym
- VOICE
- Status last verified
- May 2023
- First submitted
- 19 Nov 2020
- Last updated
- 31 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2b/3, Multicenter, Randomized, Double-blind, Placebo-controlled Study Comparing the Efficacy and Safety of Clonidine Mucoadhesive Buccal Tablet to Placebo to Prevent Chemoradiotherapy-induced Severe Oral Mucositis in Patients With Oropharyngeal Cancer
- ClinicalTrials.gov ID
- NCT04648020
- Acronym / sponsor ID
- VOICE / MNPR-301-001
- Keywords
- Mucositis, Oropharyngeal Cancer, Clonidine, Chemoradiotherapy, Severe Oral Mucositis, Monopar, Oral Mucositis, Head and Neck Cancer
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Interim Analysis did not meet the pre-defined threshold for efficacy of a 15% absolute difference in SOM prevention between Validive and placebo.
- Enrolment
- 190 participants (actual)
- Lead sponsor
- Monopar TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 11 Feb 2021 (actual)
- Primary completion
- 14 May 2023 (actual)
- Study completion
- 14 May 2023 (actual)
- First posted
- 1 Dec 2020 (actual)
- 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.
This study is being performed to evaluate the effectiveness of a new drug, clonidine HCl MBT, to prevent the onset of severe oral mucositis (SOM) in patients with oropharyngeal cancer (OPC) who are being treated with chemoradiotherapy. OPC occurs on the back of the tongue or throat and is often treated by the use of chemoradiotherapy, where radiation is localized to these areas. Radiation to the OPC affected tissues causes the release of small proteins called cytokines that cause damage to the area surrounding the tumor including the oral cavity. This damage is characterized by the formation of mucositis which includes redness, pain and ulcers in the mouth and back of the throat. In addition, as more chemoradiation is administered to treat OPC, the inability to eat a solid diet (a Grade 3 mucositis) or to consume anything at all by mouth (a Grade 4 mucositis) occurs in many patients. Collectively, Grade 3 and Grade 4 mucositis is referred to as SOM. It is a frequent, debilitating side effect of chemoradiation in OPC that may cause patients to stop or interrupt their treatment, develop other side effects like the inability to swallow, or require the increased use of pain medications. OPC survivors who have successful treatment of their tumors often develop permanent swallowing, speaking and range of motion issues that may be linked back to the inability to eat and/or drink caused by SOM during their chemoradiotherapy treatment. Clonidine may inhibit the production of cytokines that cause SOM and clonidine HCl mucoadhesive buccal tablet (MBT) has been designed to deliver sustained high levels of clonidine in the oral cavity, potentially decreasing cytokine production and leading to a decrease in the incidence of SOM. Clonidine HCl MBT is a once per day treatment provided as a tablet that a patient may self-administer to the gums, where it sticks tightly to release clonidine over many hours. The primary objective of this Phase 2b/3 study is to evaluate whether clonidine HCl MBT is more effective than placebo MBT in decreasing the incidence of SOM.
Detailed description
This is a sequential design Phase 2b/3 multicenter, randomized (1:1), double-blind, placebo-controlled, parallel group study to compare the efficacy and safety of clonidine HCl MBT to placebo MBT in the prevention of severe oral mucositis (SOM) in patients with oropharyngeal cancer (OPC) undergoing chemoradiotherapy (CRT). Best supportive care (BSC) will be allowed as per individual institutional practice with some exceptions as described in the inclusion and exclusion criteria. Eligible patients will be randomized to receive either clonidine MBT or placebo. Patients will be centrally randomized in a 1:1 ratio. The randomization will be stratified by p16 status (positive or negative). Randomized patients will be required to self-apply the study drug to the gum once a day in addition to BSC. The first application of MBT study drug will be performed on Day 1 of the CRT regimen. Each site will require the patient to follow the same local practice for BSC per Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) guidelines with some exceptions as described in the inclusion and exclusion criteria. Daily, self-administered MBT study drug will be continued once daily for the entire duration of CRT treatment; defined as from Day 1 of CRT until the last day of CRT (anticipated to be approximately 4-8 weeks depending on the patient's prescribed CRT plan). Patients will be recruited sequentially into either the Phase 2b or the Phase 3 part of the study. An interim analysis will be conducted when Phase 2b patients have either completed their CRT or discontinued from the study. The Data Monitoring Committee (DMC) will review the Phase 2b efficacy and safety data at the interim analysis and will make a recommendation on proceeding with the Phase 3 part of the study.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo Mucoadhesive Buccal TabletPlacebo Mucoadhesive Buccal Tablet given daily during chemoradiotherapy |
| Clonidine HCl Mucoadhesive Buccal Tablet (MBT) | Experimental | Drug: Clonidine HCl Mucoadhesive Buccal TabletClonidine HCl MBT given daily during chemoradiotherapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Male/Female patients of ≥ 18 years of age. Patients with histologically or pathologically confirmed squamous cell carcinoma of the oropharynx (including tonsils or the base of tongue) at one or several sites.
- Patients treated with surgical resection of their primary tumor for localized or locally advanced disease T ≥ T0 and/or N ≥ N1 without distant metastasis (M0) (American Joint Committee on Cancer - AJCC 8th edition) and initiating adjuvant concurrent CRT within 8 weeks post-operatively. Unknown primary with node-positive disease confirmed to be Squamous Cell Carcinoma would be allowed or Patients who will be treated with definitive concurrent CRT for locally advanced disease T ≥ T0 and/or N ≥ N1 M0 (American Joint Committee on Cancer - AJCC 8th edition).
- Patients eligible to receive a continuous course of external fractionated irradiation [conventional or intensity modulated radiation therapy (IMRT)] based on a daily dosing of 1.8 to 2.2 Gy/day 5 days/week in combination with cisplatin monotherapy either every 3 weeks (100 mg/m2) or weekly cisplatin (40 mg/m2). Alternative treatment regimens are allowed only if cisplatin is contraindicated. The decision on which cisplatin regimen to use in combination with IMRT and study drug/placebo will be at the discretion of the investigator.
- Radiation plan must include delivery of a cumulative dose of 60-72 Gy. The oropharynx should receive at least 50 Gy.
- Patients with adequate laboratory values defined as:
Key exclusion criteria (22 listed)
- Patients with no tumor or lesion in the oropharynx.
- Prior induction chemotherapy for treatment of current malignancy.
- Patients with planned accelerated IMRT.
- Evidence of a concomitant other malignancy and/or any prior malignancy without complete remission in the last 2 years, except adequately treated basal or squamous cell carcinoma of the skin or in situ cervical cancer.
- Patients with OM at baseline, any other oral ulceration or active oral infection (e.g., aphthous ulcers, orofacial herpes). Patients with post-operative pain of the mouth or throat are eligible.
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 |
|---|---|---|
| Clonidine HCl Mucoadhesive Buccal TabletAlso: Validive®100 μg of clonidine per tablet | Drug | Clonidine HCl Mucoadhesive Buccal Tablet (MBT) |
| Placebo Mucoadhesive Buccal TabletPlacebo | Drug | Placebo |
Primary outcome
To demonstrate the efficacy of HCl MBT to prevent SOM in OPC patients receiving CRT.
Time frame: From the first CRT treatment through the end of the study treatment period, which is estimated to be 7 weeks.
The occurrence of SOM (Yes/No), defined as any reporting of World Health Organization (WHO) Grade 3-4 OM, from the first day to the last day of CRT. The WHO mucositis grading scale will be used to assess the occurrence of SOM in this trial. The WHO grading scale grades OM from 0 to 4 according to severity of clinical observation and functional limitation, with Grade 4 = oral alimentation impossible, Grade 3 = Oral ulcers, liquid diet only, Grade 2 = Oral erythema, ulcers, solid diet tolerated, Grade 1 = Oral soreness, erythema, and Grade 0 = normal, no mucositis (no signs, no symptoms).
1 secondary outcome
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time frame: Up to 1 year after the first dose
Results and safety
The study was stopped early (reason given: Interim Analysis did not meet the pre-defined threshold for efficacy of a 15% absolute difference in SOM prevention between Validive and placebo.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 May 2023.
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.
Holli Carlson study director
Monopar Therapeutics Inc.
74 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Clonidine HCl Mucoadhesive Buccal Tablet in people with Chemoradiotherapy-Induced Severe Oral Mucositis, run by Monopar Therapeutics at 74 sites in 5 countries.
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 17 inclusion and 22 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: stopped early, as of the sponsor's last update on 31 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 74 sites in United States, France, Spain, Germany, Puerto Rico. 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.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 was stopped early (reason given: Interim Analysis did not meet the pre-defined threshold for efficacy of a 15% absolute difference in SOM prevention between Validive and placebo.). Results are not available in the source record.
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?
To demonstrate the efficacy of HCl MBT to prevent SOM in OPC patients receiving CRT. (time frame: From the first CRT treatment through the end of the study treatment period, which is estimated to be 7 weeks.). 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 31 May 2023.