Clonidine HCl MBT vs. Placebo to Prevent Chemoradiotherapy-Induced Severe Oral Mucositis in Oropharyngeal Cancer.

NCT04648020 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: MNPR-301-001
• Study Type: interventional
• Target: 190
• Locations: 5 countries
• Sites: 74

Brief 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. 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.

Conditions

Chemoradiotherapy-Induced Severe Oral Mucositis

Keywords

Mucositis; Oropharyngeal Cancer; Clonidine; Chemoradiotherapy; Severe Oral Mucositis; Monopar; Oral Mucositis; Head and Neck Cancer; Oral Cavity; Oropharynx; Mouth Sores

Outcome Measures

Primary Outcomes (1)

• 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).

  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]

  Up to 1 year after the first dose

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo Mucoadhesive Buccal Tablet given daily during chemoradiotherapy

Drug: Placebo Mucoadhesive Buccal Tablet

Clonidine HCl Mucoadhesive Buccal Tablet (MBT)

EXPERIMENTAL

Clonidine HCl MBT given daily during chemoradiotherapy

Drug: Clonidine HCl Mucoadhesive Buccal Tablet

Interventions

Clonidine HCl Mucoadhesive Buccal Tablet DRUG

100 μg of clonidine per tablet

Also known as: Validive®

Clonidine HCl Mucoadhesive Buccal Tablet (MBT)

Placebo Mucoadhesive Buccal Tablet DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.
• 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:
• a. 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.

Sponsors & Collaborators

• Monopar Therapeutics: lead

Study Sites (74)

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Orange Coast Memorial Medical Center

Fountain Valley, California, 92708, United States

Location

Long Beach Memorial Medical Center

Long Beach, California, 90806, United States

Location

Pomona Valley Hospital Medical Center

Pomona, California, 91767, United States

Location

Grand Valley Oncology

Grand Junction, Colorado, 81505, United States

Location

Christiana Care Health Services

Newark, Delaware, 19713, United States

Location

Boca Raton Regional Hospital

Boca Raton, Florida, 33486, United States

Location

Miami Cancer Institute

Miami, Florida, 33176, United States

Location

Memorial Healthcare System

Pembroke Pines, Florida, 33028, United States

Location

University Cancer & Blood Center

Athens, Georgia, 30607, United States

Location

IACT Health (Centricity Research)

Columbus, Georgia, 31904, United States

Location

Decatur Memorial Hospital

Decatur, Illinois, 62526, United States

Location

Edward Elmhurst Health

Elmhurst, Illinois, 60126, United States

Location

NorthShore University Health Systems

Evanston, Illinois, 60201, United States

Location

AMITA Health

Hinsdale, Illinois, 60521, United States

Location

UnityPoint Health

Cedar Rapids, Iowa, 52403, United States

Location

Des Moines Oncology Research Association

Des Moines, Iowa, 50309, United States

Location

East Jefferson General Hospital

Metairie, Louisiana, 70006, United States

Location

Louisiana State University Health - Shreveport

Shreveport, Louisiana, 71103, United States

Location

Willis-Knighton Cancer Center

Shreveport, Louisiana, 71103, United States

Location

Greater Baltimore Medical Center

Baltimore, Maryland, 21204, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Cox Medical Centers

Springfield, Missouri, 65807, United States

Location

Summit Health

Florham Park, New Jersey, 07932, United States

Location

New York Cancer and Blood Specialists

New York, New York, 10028, United States

Location

Northwell Health

New York, New York, 11042, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27514, United States

Location

Novant Health Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

CaroMont Regional Medical Center

Gastonia, North Carolina, 28054, United States

Location

Novant Health Cancer Institute - Forsyth

Winston-Salem, North Carolina, 27103, United States

Location

Summa Health System

Akron, Ohio, 44304, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45219, United States

Location

Mercy Health

Youngstown, Ohio, 44501, United States

Location

Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Oklahoma Cancer Specialists

Tulsa, Oklahoma, 74146, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

AHN Cancer Institute - Allegheny General

Pittsburgh, Pennsylvania, 15212, United States

Location

Mary Hillman Radiation Oncology Center at UPMC Shadyside

Pittsburgh, Pennsylvania, 15232, United States

Location

Reading Hospital

West Reading, Pennsylvania, 19611, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Charleston Oncology

Charleston, South Carolina, 29406, United States

Location

Ballad Health

Johnson City, Tennessee, 37604, United States

Location

Hendrick Cancer Center

Abilene, Texas, 79601, United States

Location

Eastern Virginia Medical School

Norfolk, Virginia, 23507, United States

Location

PeaceHealth

Bellingham, Washington, 98225, United States

Location

Providence Regional Cancer Partnership

Everett, Washington, 98201, United States

Location

Benaroya Research Institute at Virginia Mason

Seattle, Washington, 98101, United States

Location

HSHS St. Vincent Hospital Cancer Centers at HSHS St. Vincent Hospital

Green Bay, Wisconsin, 54301, United States

Location

Institut Andree Dutreix / Centre de Cancerologie Dunkerque

Coudekerque-Branche, Dunkerque, 59210, France

Location

Centre Hospitalier Universitaire Amiens-Picardie

Amiens, 80054, France

Location

Centre Hospitalier Universitaire Morvan / Centre Hospitalier Universitaire de Brest

Brest, 29609, France

Location

Centre hopitalier intercommunal de Créteil

Créteil, 94000, France

Location

Centre Hospitalier de Dax-Côte d'Argent

Dax, 40100, France

Location

Clinique François Chénieux

Limoges, 87039, France

Location

Hôpital Saint Joseph

Marseille, 13008, France

Location

Centre Hospitalier Universitaire La miletrie

Nice, 06000, France

Location

Institut Jean Godinot

Reims, 51100, France

Location

CHU de Saint Etienne

Saint-Priest-en-Jarez, 42270, France

Location

Institut Gustave Roussy, Desmoulins

Villejuif, 94800, France

Location

Universitatsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Klinikum Kassel GmbH

Kassel, 34125, Germany

Location

Caritas Klinikum Saarbrucken St. Theresia

Saarbrücken, 66113, Germany

Location

Ponce Medical School Foundation

Ponce, 00717, Puerto Rico

Location

Hospital Universitari Son Espases

Palma, Balearic Islands, 07120, Spain

Location

Hospital Universitario Cruces de Bilbao

Barakaldo, Bizkaia, 48903, Spain

Location

Hospital Meixoeiro

Vigo, Pontevedra, 36214, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Institut Català d'Oncologia Hospitalet (Hospital Duran i Reynals)

Barcelona, 08908, Spain

Location

Hospital Universitario Quirónsalud Madrid

Madrid, 28223, Spain

Location

Hospital Universitario Puerta de Hierro Majadahonda

Majadahonda, 28222, Spain

Location

Hospital Universitari Son Llàtzer

Palma de Mallorca, 07098, Spain

Location

Hospital Complejo Universitario de Navarra

Pamplona, 31008, Spain

Location

Hospital de Donostia

San Sebastián, 20014, Spain

Location

Hospital Clínico Universitario Santiago de Compostela

Santiago de Compostela, 15706, Spain

Location

MeSH Terms

Conditions

Mucositis; Oropharyngeal Neoplasms; Stomatitis; Head and Neck Neoplasms; Oral Ulcer

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Mouth Diseases; Stomatognathic Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Neoplasms by Site; Neoplasms; Pharyngeal Diseases; Otorhinolaryngologic Diseases

Study Officials

• Holli Carlson

  Monopar Therapeutics Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2020
• First Posted: December 1, 2020
• Study Start: February 11, 2021
• Primary Completion: May 14, 2023
• Study Completion: May 14, 2023
• Last Updated: May 31, 2023

Record last verified: 2023-05

Locations

ES (11); DE (3); US (48); PR (1); FR (11)