Brief Summary
The purpose of this study is to determine if RRx-001, which is added on to the cisplatin and radiation treatment, reduces the duration or length of severe oral mucositis in patients with head and neck cancers. All patients in this study will receive 7 weeks of standard of care radiation therapy given with the chemotherapy agent, cisplatin. Patients in arms 1, 2 and 3 will also receive RRx-001 on different schedules.
Brief Title
Safety and Efficacy of RRx-001 in the Attenuation of Oral Mucositis in Patients Receiving Chemoradiation for the Treatment of Oral Cancers
Detailed Description
The standard treatment for head and neck cancer currently includes a chemotherapy drug called cisplatin that is given by intravenous (IV) infusion and radiation, which is delivered from a machine that precisely targets the tumor. One common and unfortunate side effect of treatment with cisplatin and radiation is oral mucositis, which refers to irritation of the lining of the mouth. Oral mucositis is a serious problem 1) because the open mouth sores from oral mucositis may lead to severe pain, nutritional problems and dehydration from an inability to eat and drink, an increased risk of infection from bacteria and fungus and delay or discontinuation of treatment and 2) because there is only one approved therapy to treat or prevent it.
Completion Date
Completion Date Type
Actual
Conditions
Oral Mucositis
Eligibility Criteria
Inclusion Criteria:
1. Pathologically confirmed diagnosis of squamous cell carcinoma (SCC) of the oral cavity and oropharynx Note: Patients with unknown primary tumors whose treatment plan matches the requirements specified in Inclusion Criterion #3 below are eligible for the trial
2. Treatment planned to include standard cisplatin monotherapy administered either every three weeks (100 mg/m2 for 3 doses) with concomitant radiation delivered as a continuous course of IMRT with single daily fractions of 2.0 to 2.2 Gy with a cumulative radiation dose between 60 Gy and 72 Gy. Planned radiation treatment fields must include at least two oral sites (buccal mucosa, floor of mouth, tongue, soft palate) that are each planned to receive a total of \> 55 Gy. Patients who have had prior surgery are eligible, provided they have fully recovered from surgery, and patients who may have surgery in the future are eligible.
3. ECOG performance status ≤ 2.
4. Participants must have adequate organ and marrow function as defined below:
A. Absolute neutrophil count (ANC) \>1,500 / mm3 B. Platelets \> 100,000 / mm3 C. Hemoglobin ≥ 9.0 g/dL
5. Adequate renal and liver function as indicated by:
A. Serum creatinine acceptable for treatment with cisplatin per institutional guidelines) B. Total bilirubin ≤ 1.5 x upper-normal limit (ULN) C. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN D. Alkaline phosphatase ≤ 2.5 x ULN
6. Human papilloma virus (HPV) status in tumor has been documented using tumor immunohistochemistry for HPV-p16 or other accepted test for patients with cancers of the oropharynx, base of tongue, or unknown primary.
7. Age 18 years or older
8. Patient must consent to the access, review and analysis of previous medical and cancer history, including imaging data by the sponsor or a third party nominated by the sponsor.
9. Ability to understand and sign a written informed consent document.
10. Women of child-bearing potential and men with partners of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy.
Note: A woman of child-bearing potential is any female (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
* Has not undergone a hysterectomy or bilateral oophorectomy; or
* Has not been postmenopausal for at least 12 consecutive months
11. Adequate visual access to permit examination of the following oral cavity sites: lips, buccal mucosa, floor of mouth, ventral and lateral tongue and soft palate.
Exclusion Criteria:
1. Prior radiation to the head and neck
2. Tumor of the lips, nasopharynx, hypopharynx, larynx, or salivary glands
3. Patients with simultaneous primaries or bilateral tumors
4. Metastatic disease (M1) Stage IV
5. Malignant tumors other than HNC within the last 5 years, unless treated definitively and with low risk of recurrence in the judgment of the treating investigator
6. Presence of oral mucositis (WHO Score ≥ Grade 1) or other oral mucosal ulceration at study entry
7. Grade 3 or 4 dysphagia or odynophagia (National Cancer Institute Common Toxicity Criteria, version 5.0) or inability to eat a normal diet
8. Requirement at baseline for parenteral or gastrointestinal tube-delivered nutrition for any reason
9. Known history of HIV or active hepatitis B/C (patients who have been vaccinated for hepatitis B and do not have a history of infection are eligible)
10. Any significant medical diseases or conditions, as assessed by the investigators and sponsor that would substantially increase the medical risks of participating in this study (i.e., uncontrolled diabetes, NYHA II-IV congestive heart failure, myocardial infarction within 6 months of study, severe chronic pulmonary disease or active uncontrolled infection, uncontrolled or clinically relevant pulmonary edema).
11. Pregnant or nursing
12. Untreated active oral or dental infection, including severe tooth decay (caries)
13. Known allergies or intolerance to cisplatin and similar platinum-containing compounds
14. Evidence of immediate life-threatening disease or a life expectancy of less than 3 months
15. Receipt of unapproved or off-label medication within 30 days prior to start of study treatment
16. Sjogren syndrome
1. Pathologically confirmed diagnosis of squamous cell carcinoma (SCC) of the oral cavity and oropharynx Note: Patients with unknown primary tumors whose treatment plan matches the requirements specified in Inclusion Criterion #3 below are eligible for the trial
2. Treatment planned to include standard cisplatin monotherapy administered either every three weeks (100 mg/m2 for 3 doses) with concomitant radiation delivered as a continuous course of IMRT with single daily fractions of 2.0 to 2.2 Gy with a cumulative radiation dose between 60 Gy and 72 Gy. Planned radiation treatment fields must include at least two oral sites (buccal mucosa, floor of mouth, tongue, soft palate) that are each planned to receive a total of \> 55 Gy. Patients who have had prior surgery are eligible, provided they have fully recovered from surgery, and patients who may have surgery in the future are eligible.
3. ECOG performance status ≤ 2.
4. Participants must have adequate organ and marrow function as defined below:
A. Absolute neutrophil count (ANC) \>1,500 / mm3 B. Platelets \> 100,000 / mm3 C. Hemoglobin ≥ 9.0 g/dL
5. Adequate renal and liver function as indicated by:
A. Serum creatinine acceptable for treatment with cisplatin per institutional guidelines) B. Total bilirubin ≤ 1.5 x upper-normal limit (ULN) C. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN D. Alkaline phosphatase ≤ 2.5 x ULN
6. Human papilloma virus (HPV) status in tumor has been documented using tumor immunohistochemistry for HPV-p16 or other accepted test for patients with cancers of the oropharynx, base of tongue, or unknown primary.
7. Age 18 years or older
8. Patient must consent to the access, review and analysis of previous medical and cancer history, including imaging data by the sponsor or a third party nominated by the sponsor.
9. Ability to understand and sign a written informed consent document.
10. Women of child-bearing potential and men with partners of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy.
Note: A woman of child-bearing potential is any female (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
* Has not undergone a hysterectomy or bilateral oophorectomy; or
* Has not been postmenopausal for at least 12 consecutive months
11. Adequate visual access to permit examination of the following oral cavity sites: lips, buccal mucosa, floor of mouth, ventral and lateral tongue and soft palate.
Exclusion Criteria:
1. Prior radiation to the head and neck
2. Tumor of the lips, nasopharynx, hypopharynx, larynx, or salivary glands
3. Patients with simultaneous primaries or bilateral tumors
4. Metastatic disease (M1) Stage IV
5. Malignant tumors other than HNC within the last 5 years, unless treated definitively and with low risk of recurrence in the judgment of the treating investigator
6. Presence of oral mucositis (WHO Score ≥ Grade 1) or other oral mucosal ulceration at study entry
7. Grade 3 or 4 dysphagia or odynophagia (National Cancer Institute Common Toxicity Criteria, version 5.0) or inability to eat a normal diet
8. Requirement at baseline for parenteral or gastrointestinal tube-delivered nutrition for any reason
9. Known history of HIV or active hepatitis B/C (patients who have been vaccinated for hepatitis B and do not have a history of infection are eligible)
10. Any significant medical diseases or conditions, as assessed by the investigators and sponsor that would substantially increase the medical risks of participating in this study (i.e., uncontrolled diabetes, NYHA II-IV congestive heart failure, myocardial infarction within 6 months of study, severe chronic pulmonary disease or active uncontrolled infection, uncontrolled or clinically relevant pulmonary edema).
11. Pregnant or nursing
12. Untreated active oral or dental infection, including severe tooth decay (caries)
13. Known allergies or intolerance to cisplatin and similar platinum-containing compounds
14. Evidence of immediate life-threatening disease or a life expectancy of less than 3 months
15. Receipt of unapproved or off-label medication within 30 days prior to start of study treatment
16. Sjogren syndrome
Inclusion Criteria
Inclusion Criteria:
1. Pathologically confirmed diagnosis of squamous cell carcinoma (SCC) of the oral cavity and oropharynx Note: Patients with unknown primary tumors whose treatment plan matches the requirements specified in Inclusion Criterion #3 below are eligible for the trial
2. Treatment planned to include standard cisplatin monotherapy administered either every three weeks (100 mg/m2 for 3 doses) with concomitant radiation delivered as a continuous course of IMRT with single daily fractions of 2.0 to 2.2 Gy with a cumulative radiation dose between 60 Gy and 72 Gy. Planned radiation treatment fields must include at least two oral sites (buccal mucosa, floor of mouth, tongue, soft palate) that are each planned to receive a total of \> 55 Gy. Patients who have had prior surgery are eligible, provided they have fully recovered from surgery, and patients who may have surgery in the future are eligible.
3. ECOG performance status ≤ 2.
4. Participants must have adequate organ and marrow function as defined below:
A. Absolute neutrophil count (ANC) \>1,500 / mm3 B. Platelets \> 100,000 / mm3 C. Hemoglobin ≥ 9.0 g/dL
5. Adequate renal and liver function as indicated by:
A. Serum creatinine acceptable for treatment with cisplatin per institutional guidelines) B. Total bilirubin ≤ 1.5 x upper-normal limit (ULN) C. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN D. Alkaline phosphatase ≤ 2.5 x ULN
6. Human papilloma virus (HPV) status in tumor has been documented using tumor immunohistochemistry for HPV-p16 or other accepted test for patients with cancers of the oropharynx, base of tongue, or unknown primary.
7. Age 18 years or older
8. Patient must consent to the access, review and analysis of previous medical and cancer history, including imaging data by the sponsor or a third party nominated by the sponsor.
9. Ability to understand and sign a written informed consent document.
10. Women of child-bearing potential and men with partners of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy.
Note: A woman of child-bearing potential is any female (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
* Has not undergone a hysterectomy or bilateral oophorectomy; or
* Has not been postmenopausal for at least 12 consecutive months
11. Adequate visual access to permit examination of the following oral cavity sites: lips, buccal mucosa, floor of mouth, ventral and lateral tongue and soft palate.
1. Pathologically confirmed diagnosis of squamous cell carcinoma (SCC) of the oral cavity and oropharynx Note: Patients with unknown primary tumors whose treatment plan matches the requirements specified in Inclusion Criterion #3 below are eligible for the trial
2. Treatment planned to include standard cisplatin monotherapy administered either every three weeks (100 mg/m2 for 3 doses) with concomitant radiation delivered as a continuous course of IMRT with single daily fractions of 2.0 to 2.2 Gy with a cumulative radiation dose between 60 Gy and 72 Gy. Planned radiation treatment fields must include at least two oral sites (buccal mucosa, floor of mouth, tongue, soft palate) that are each planned to receive a total of \> 55 Gy. Patients who have had prior surgery are eligible, provided they have fully recovered from surgery, and patients who may have surgery in the future are eligible.
3. ECOG performance status ≤ 2.
4. Participants must have adequate organ and marrow function as defined below:
A. Absolute neutrophil count (ANC) \>1,500 / mm3 B. Platelets \> 100,000 / mm3 C. Hemoglobin ≥ 9.0 g/dL
5. Adequate renal and liver function as indicated by:
A. Serum creatinine acceptable for treatment with cisplatin per institutional guidelines) B. Total bilirubin ≤ 1.5 x upper-normal limit (ULN) C. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN D. Alkaline phosphatase ≤ 2.5 x ULN
6. Human papilloma virus (HPV) status in tumor has been documented using tumor immunohistochemistry for HPV-p16 or other accepted test for patients with cancers of the oropharynx, base of tongue, or unknown primary.
7. Age 18 years or older
8. Patient must consent to the access, review and analysis of previous medical and cancer history, including imaging data by the sponsor or a third party nominated by the sponsor.
9. Ability to understand and sign a written informed consent document.
10. Women of child-bearing potential and men with partners of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy.
Note: A woman of child-bearing potential is any female (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
* Has not undergone a hysterectomy or bilateral oophorectomy; or
* Has not been postmenopausal for at least 12 consecutive months
11. Adequate visual access to permit examination of the following oral cavity sites: lips, buccal mucosa, floor of mouth, ventral and lateral tongue and soft palate.
Gender
All
Gender Based
false
Keywords
head and neck cancer
squamous
neck cancer
oral cancer
mucositis
sores
mouth
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT03515538
Org Class
Industry
Org Full Name
EpicentRx, Inc.
Org Study Id
PR-001
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 2a Randomized, Parallel Group, Open Label, Multicenter Study to Assess the Safety and Efficacy of RRx-001 in the Attenuation of Oral Mucositis in Patients Receiving Chemoradiation for the Treatment of Locally Advanced Squamous Cell Carcinoma of the Oral Cavity or Oropharynx
Primary Outcomes
Outcome Description
Duration in days of severe oral mucositis (SOM). Defined as oral mucositis grade 3 or 4 on the WHO Mucositis Grading Scale which comprises 5 grades: 0 = none, 1= oral soreness, erythema, 2 = oral erythema, ulcers, solid diet tolerated, 3 = oral ulcers, liquid diet only, and 4 = oral alimentation impossible. Severe Oral Mucositis duration is obtained by totaling the number of days a given patient experiences oral mucositis grade 3 or 4 during the randomized treatment period. Higher Severe Oral Mucositis duration numbers are indicative of worst outcomes. The total Severe Oral Mucositis duration for a given patient will range between 0 days and the maximum number of days the patient participated in the randomized treatment period.
Outcome Measure
Duration of Severe Oral Mucositis (SOM)
Outcome Time Frame
From start of treatment through 28 days post treatment for up to 11 weeks from Start of Treatment
Secondary Outcomes
Outcome Description
Time to onset of Severe Oral Mucositis defined as time (in days) from randomization to the first observed Severe Oral Mucositis. Longer Severe Oral Mucositis onset times are indicative of a better outcome. The time to onset of Severe Oral Mucositis for a given patient will range between 0 days and the maximum number of days the patient participated in the randomized treatment period.
Outcome Time Frame
Time from Day 1 to Oral Mucositis Onset (up to 8 weeks)
Outcome Measure
Time to Onset of Severe Oral Mucositis
Outcome Description
Incidence of Severe Oral Mucositis defined as the number of patients who experienced a Severe Oral Mucositis grade 4 during the randomized treatment period.
Outcome Time Frame
Baseline through end of treatment (up to 11 weeks). Data collected every week.
Outcome Measure
Incidence of Severe Oral Mucositis
Outcome Description
Opioid use from the time to onset (TTO) and duration of opioid use among patients who were not taking opioids at radiation start or who required a second opioid during active treatment.
Outcome Time Frame
Baseline through end of radiation treatment (through 8 weeks). Data collected every week.
Outcome Measure
Opioid Use
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
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
Rafi Kabarriti
Investigator Email
RKABARRI@MONTEFIORE.ORG
Investigator Phone