Brief Summary
The purpose of this study is to evaluate the efficacy and safety of Clonidine Lauriad® to treat chemoradiation therapy induced severe oral mucositis in patients with head and neck cancer.
Brief Title
Efficacy and Safety Study of Clonidine Lauriad® to Treat Oral Mucositis
Categories
Completion Date
Completion Date Type
Actual
Conditions
Oral Mucositis
Eligibility Criteria
Inclusion Criteria:
* Male or female
* Aged \> 18 years
* Suffering from a newly diagnosed squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx histologically-confirmed and having undergone resective surgery
* Prior neoadjuvant chemotherapy allowed provided that, the patient did not experience a World Health Organization (WHO) grade \> 2 oral mucositis during the neoadjuvant therapy.
* Patient eligible to receive concurrent chemo-radiation defined as:
1. A continuous course of conventional external beam irradiation (IMRT eligible) with a minimum cumulative radiation dose of 50 Gy or a maximum of 70 Gy, based on a daily dosing between 1.8 and 2.2 Gy combined with platinum based chemotherapy on a weekly or tri-weekly cycles.
2. Planned radiation treatment fields must include at least two oral tissue sites (among right or left buccal mucosa, floor of mouth, tongue, right or left soft palate) with each site receiving a total of 50 Gy or a maximum of 70 Gy. The radiation treatment plan will be reviewed by a designated radiation oncologist.
* Eastern Cooperative Oncology Group (ECOG) performance status ≤2
* Screening laboratory tests:
1. Haemoglobin ≥ 10g/dL
2. Absolute neutrophil counts ≥ 1500 cells/mm3
3. Platelets ≥ 100.000/mm3
4. Conjugated bilirubin ≤ 2 times Upper Limit of Normal (ULN)
5. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 ULN
6. Negative serum pregnancy test
* Women of child bearing potential must have effective contraception method (oral or device)
* Signed written informed consent
Exclusion Criteria:
* Tumours of the lips, sinuses, salivary glands
* Prior radiation of the head and neck area
* Curative surgery less than 2 weeks or more than 15 weeks prior to the initiation of radiation therapy-chemotherapy (RT-CT)
* Presence of active infectious disease
* Presence of active oral infectious disease, including oropharyngeal candidiasis and/or orofacial herpes
* Presence of oral mucositis
* Known or suspected chronic viral diseases including HIV
* Systolic blood pressure \< 100 mmHg and/or Diastolic blood pressure \< 50 mmHg
* Recent stroke within the last 6 months
* Bradyarrhythmia (\<60 b/min), including sinus node dysfunction or atrioventricular (AV) nodal conduction block 2nd or 3rd degree
* Subjects with orthostatic hypotension, defined by a decrease of systolic BP and/or diastolic BP above 20 mmHg when the patient stands up
* Renal insufficiency (creatinine blood level \> 1.5ULN)
* Ongoing heavy alcohol consumption (\>100g alcohol/day)
* Administration of any concomitant treatment likely to interfere with clonidine
* Known hypersensitivity to clonidine, history of allergy or intolerance to milk proteins or any other component of the product
* Presence of severe or uncontrolled depression
* Pregnant or breast-feeding women
* Inability to give informed consent or comply with study requirements
* Unable or unwilling to comply with follow-up visits
* Participation to a clinical trial within 30 days prior to randomization and during the entire duration of the study
* Male or female
* Aged \> 18 years
* Suffering from a newly diagnosed squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx histologically-confirmed and having undergone resective surgery
* Prior neoadjuvant chemotherapy allowed provided that, the patient did not experience a World Health Organization (WHO) grade \> 2 oral mucositis during the neoadjuvant therapy.
* Patient eligible to receive concurrent chemo-radiation defined as:
1. A continuous course of conventional external beam irradiation (IMRT eligible) with a minimum cumulative radiation dose of 50 Gy or a maximum of 70 Gy, based on a daily dosing between 1.8 and 2.2 Gy combined with platinum based chemotherapy on a weekly or tri-weekly cycles.
2. Planned radiation treatment fields must include at least two oral tissue sites (among right or left buccal mucosa, floor of mouth, tongue, right or left soft palate) with each site receiving a total of 50 Gy or a maximum of 70 Gy. The radiation treatment plan will be reviewed by a designated radiation oncologist.
* Eastern Cooperative Oncology Group (ECOG) performance status ≤2
* Screening laboratory tests:
1. Haemoglobin ≥ 10g/dL
2. Absolute neutrophil counts ≥ 1500 cells/mm3
3. Platelets ≥ 100.000/mm3
4. Conjugated bilirubin ≤ 2 times Upper Limit of Normal (ULN)
5. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 ULN
6. Negative serum pregnancy test
* Women of child bearing potential must have effective contraception method (oral or device)
* Signed written informed consent
Exclusion Criteria:
* Tumours of the lips, sinuses, salivary glands
* Prior radiation of the head and neck area
* Curative surgery less than 2 weeks or more than 15 weeks prior to the initiation of radiation therapy-chemotherapy (RT-CT)
* Presence of active infectious disease
* Presence of active oral infectious disease, including oropharyngeal candidiasis and/or orofacial herpes
* Presence of oral mucositis
* Known or suspected chronic viral diseases including HIV
* Systolic blood pressure \< 100 mmHg and/or Diastolic blood pressure \< 50 mmHg
* Recent stroke within the last 6 months
* Bradyarrhythmia (\<60 b/min), including sinus node dysfunction or atrioventricular (AV) nodal conduction block 2nd or 3rd degree
* Subjects with orthostatic hypotension, defined by a decrease of systolic BP and/or diastolic BP above 20 mmHg when the patient stands up
* Renal insufficiency (creatinine blood level \> 1.5ULN)
* Ongoing heavy alcohol consumption (\>100g alcohol/day)
* Administration of any concomitant treatment likely to interfere with clonidine
* Known hypersensitivity to clonidine, history of allergy or intolerance to milk proteins or any other component of the product
* Presence of severe or uncontrolled depression
* Pregnant or breast-feeding women
* Inability to give informed consent or comply with study requirements
* Unable or unwilling to comply with follow-up visits
* Participation to a clinical trial within 30 days prior to randomization and during the entire duration of the study
Inclusion Criteria
Inclusion Criteria:
* Male or female
* Aged \> 18 years
* Suffering from a newly diagnosed squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx histologically-confirmed and having undergone resective surgery
* Prior neoadjuvant chemotherapy allowed provided that, the patient did not experience a World Health Organization (WHO) grade \> 2 oral mucositis during the neoadjuvant therapy.
* Patient eligible to receive concurrent chemo-radiation defined as:
1. A continuous course of conventional external beam irradiation (IMRT eligible) with a minimum cumulative radiation dose of 50 Gy or a maximum of 70 Gy, based on a daily dosing between 1.8 and 2.2 Gy combined with platinum based chemotherapy on a weekly or tri-weekly cycles.
2. Planned radiation treatment fields must include at least two oral tissue sites (among right or left buccal mucosa, floor of mouth, tongue, right or left soft palate) with each site receiving a total of 50 Gy or a maximum of 70 Gy. The radiation treatment plan will be reviewed by a designated radiation oncologist.
* Eastern Cooperative Oncology Group (ECOG) performance status ≤2
* Screening laboratory tests:
1. Haemoglobin ≥ 10g/dL
2. Absolute neutrophil counts ≥ 1500 cells/mm3
3. Platelets ≥ 100.000/mm3
4. Conjugated bilirubin ≤ 2 times Upper Limit of Normal (ULN)
5. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 ULN
6. Negative serum pregnancy test
* Women of child bearing potential must have effective contraception method (oral or device)
* Signed written informed consent
* Male or female
* Aged \> 18 years
* Suffering from a newly diagnosed squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx histologically-confirmed and having undergone resective surgery
* Prior neoadjuvant chemotherapy allowed provided that, the patient did not experience a World Health Organization (WHO) grade \> 2 oral mucositis during the neoadjuvant therapy.
* Patient eligible to receive concurrent chemo-radiation defined as:
1. A continuous course of conventional external beam irradiation (IMRT eligible) with a minimum cumulative radiation dose of 50 Gy or a maximum of 70 Gy, based on a daily dosing between 1.8 and 2.2 Gy combined with platinum based chemotherapy on a weekly or tri-weekly cycles.
2. Planned radiation treatment fields must include at least two oral tissue sites (among right or left buccal mucosa, floor of mouth, tongue, right or left soft palate) with each site receiving a total of 50 Gy or a maximum of 70 Gy. The radiation treatment plan will be reviewed by a designated radiation oncologist.
* Eastern Cooperative Oncology Group (ECOG) performance status ≤2
* Screening laboratory tests:
1. Haemoglobin ≥ 10g/dL
2. Absolute neutrophil counts ≥ 1500 cells/mm3
3. Platelets ≥ 100.000/mm3
4. Conjugated bilirubin ≤ 2 times Upper Limit of Normal (ULN)
5. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 ULN
6. Negative serum pregnancy test
* Women of child bearing potential must have effective contraception method (oral or device)
* Signed written informed consent
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT01385748
Org Class
Industry
Org Full Name
Valerio Therapeutics
Org Study Id
BA2009/28/01
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase II, Multi-center, Randomised, Double-blind, Placebo-controlled Study Comparing the Efficacy and Safety of Clonidine Lauriad® 50 μg and 100 μg Mucoadhesive Buccal Tablet (MBT) Applied Once Daily to Those of Placebo in the Prevention and Treatment of Chemoradiation Therapy Induced Oral Mucositis in Patients With Head and Neck Cancer
Primary Outcomes
Outcome Description
The primary endpoint planned in the protocol was the percentage of participants with an oral mucositis score greater than or equal to 3 using the WHO oral mucositis severity scale at a cumulative radiation dose of 50 Gy. This was modified by protocol amendment to the cumulative radiation dose at which a WHO score greater than or equal to 3 was first observed. This change was made to account for the fact that in real practice most patients receive a cumulative dose between 60 and 70 Gy. The presence of grade 3 or 4 oral mucositis was assessed twice weekly during the active phase (radiotherapy) by a trained radiation oncologist or an ear nose and throat specialist who took into account the field of radiation treatment. WHO score 3 = oral ulcers, liquid diet only; WHO score 4 = oral alimentation impossible. Each assessment was associated with the actual cumulative dose of radiotherapy.
Outcome Measure
Cumulative Radiation Dose at Which Severe Oral Mucositis (World Health Organization [WHO] Score ≥ 3) Was First Observed
Outcome Time Frame
8 weeks
Secondary Outcomes
Outcome Description
Opioid use was recorded twice weekly during the active phase (radiotherapy)
Outcome Time Frame
8 weeks
Outcome Measure
At Least One Opioid Use (Class 3 Analgesic)
Outcome Description
Opioid use was recorded twice weekly for up to 8 weeks during the active phase (radiotherapy). The sum of non-missing total cumulative doses across all class 3 analgesics recorded for the considered participant is reported.
Outcome Time Frame
8 weeks
Outcome Measure
Opioid Use: Minimal Total Cumulative Dose Administered (Mean, Standard Deviation)
Outcome Description
Opioid use was recorded twice weekly for up to 8 weeks during the active phase (radiotherapy). The sum of non-missing total cumulative doses across all class 3 analgesics recorded for the considered participant is reported.
Outcome Time Frame
8 weeks
Outcome Measure
Opioid Use: Minimal Total Cumulative Dose Administered (Median, Range)
Outcome Description
After the end-of study visit, the investigator center collects OS follow-up data for each patient who has consented to participate in the follow-up data collection. the OS follow-up period was still ongoing at time of the primary analysis and ended in Nov 2016. The analysis was condicted on the ITT population. The overall survival was evaluate every 6 months after last subject completed in patients who has consented to participate .
Outcome Time Frame
2 years
Outcome Measure
Overall Survival
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Madhur Garg
Investigator Email
mgarg@montefiore.org
Investigator Phone