Advanced Cancers
Conditions
Keywords
Advanced Cancers, Mucositis, Esophagitis, mTOR Inhibitor-based Regimen, Radiation to the Esophagus, Thoracic malignancies, Placebo, Glutamine, Enterex, Glutapak-10, NutreStore, Resource, GlutaSolve, Sympt-X G.I., Sympt-X, Questionnaires, Surveys
Brief summary
The goal of this clinical research study is to learn if glutamine can help control and prevent sores, blisters, or inflammation in your mouth or esophagus due to your current treatment. In this study, glutamine will be compared to a placebo. A placebo is not a drug. It looks like the drug but is not designed to treat any disease or illness. It is designed to be compared with a study drug to learn if the study drug has any real effect.
Detailed description
Study Groups: If you are found to be eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 study groups. You will have an equal chance of being assigned to either group: * If you are in Group 1, you will receive glutamine. * If you are in Group 2, you will receive a placebo. Neither you nor the study staff will know if you are receiving the study drug or the placebo. However, if needed for your safety, the study staff will be able to find out what you are receiving. Study Drug Administration: Glutamine or the placebo will be taken as a sugary drink by mouth. You will take the drink twice daily starting the day you first receive your anti-cancer therapy or radiation treatment. You will mix one scoop of powder with 25-100 milliliters (about 2-6 tablespoons) of water. If you are in the chemotherapy group, you will swish the drink for 10 seconds and swallow. If you are in the radiation group, you will swallow the drink in small amounts several times. Study Visits: At every visit, you will be asked about any side effects you may be having and about any other drugs you may be taking. Chemotherapy Group: On Days 1, 8, and 22 of Cycle 1: * You will have a mouth exam. * Your weight will be recorded. On Day 15 of Cycle 1: * You will have a mouth exam. * Your weight will be recorded. * You will complete a quality of life questionnaire. On Day 1 of Cycle 2 and beyond: * You will have a mouth exam. * Your weight will be recorded. * If the doctor thinks it is needed, blood (about 2 teaspoons) will be drawn for routine tests. * You will complete a quality of life questionnaire. * You will complete a survey about how you feel about the study drug. This should take about 5-10 minutes to complete. * If the doctor thinks it is needed, you will have a photograph of your mouth taken. After 3 months of chemotherapy: * You will complete a quality of life questionnaire. After 6 months of chemotherapy: * Your weight will be recorded. * You will complete a quality of life questionnaire. Follow-Up: For your follow-up questionnaires at Day 1 of every Cycle, at 3 and 6 months, and during the End-of-Study visit, you may be called by the study team. This call should last about 5-10 minutes. Radiation Therapy Group: On Weeks 1, 2, 4, and 6 of Radiation: * You will be asked if you have inflammation of your esophagus. * Your weight will be recorded. * If the doctor thinks it is needed, blood (about 2 teaspoons) will be drawn for routine tests. On Weeks 3 and 5 of Radiation: * You will be asked if you have inflammation of your esophagus. * Your weight will be recorded. * If the doctor thinks it is needed, blood (about 2 teaspoons) will be drawn for routine tests. * You will complete a quality of life questionnaire. * You will complete a survey about how you feel about the study drug. On Week 7 of Radiation: * You will be asked if you have inflammation of your esophagus. * Your weight will be recorded. * If the doctor thinks it is needed, blood (about 2 teaspoons) will be drawn for routine tests. * You will complete a quality of life questionnaire. * You will complete a survey about how you feel about the study drug. 1 month after your radiation has ended: * You will be asked if you have inflammation of your esophagus. * Your weight will be recorded. * If the doctor thinks it is needed, blood (about 2 teaspoons) will be drawn for routine tests. * You will complete a quality of life questionnaire. * You will complete a survey about how you feel about the study drug. 3 months after your radiation has ended: * You will complete a quality of life questionnaire. Follow-Up: For your follow-up questionnaires at 1 and 3 months and during the End-of-Study visit, you may be called by the study team. This call should last about 5-10 minutes. Length of Study: You may continue taking the study drug for as long as the doctor thinks it is in your best interest. You will continue taking the glutamine or placebo for 4 weeks after the completion of your anti-cancer therapy or radiation treatment. If you stop chemotherapy or radiation before completion of the intended study period, you will continue to take the study drug for 4 weeks. If you develop severe sores, blisters, or inflammation in your mouth or esophagus, you will be removed from the study, and the doctor will give you another medication for your sores and blisters. Your participation on the study will be over 6 months after completion of your therapy. End-of-Study Visit: After you are off study, you will have an end-of-study visit. For the radiation group, this will be 6 months after radiation therapy. For the chemotherapy group, this is 4 weeks after the last dose. * Your weight will be recorded. * If the doctor thinks it is needed, blood (about 2 teaspoons) will be drawn for routine tests. * You will complete a quality of life questionnaire. * If you are in the chemotherapy group, you will have a mouth exam. This is an investigational study. Glutamine is FDA approved and commercially available for the treatment of short bowel syndrome. Its use to treat mouth sores and inflammation of the esophagus is investigational. Up to 180 patients will take part in this study. All will be enrolled at MD Anderson.
Interventions
OTHERPlacebo
mTOR Inhibitor Patient Group: Participants receive placebo beginning on Day 1 of an mTOR inhibitor based therapy. Placebo taken as a sugary drink by mouth. Participant will take the drink twice daily starting first day anti-cancer therapy received. Participant to swish the drink for 10 seconds and swallow. Four weeks of treatment constitute 1 cycle for participants on mTOR inhibitor therapy.
DRUGGlutamine
mTOR Inhibitor Patient Group - Glutamine taken as a sugary drink by mouth. Participant will take the drink twice daily starting first day anti-cancer therapy received. Participant to swish the drink for 10 seconds and swallow. Four weeks of treatment constitute 1 cycle for participants on mTOR inhibitor therapy.
BEHAVIORALQuestionnaires
Questionnaire completion for mTOR Inhibitor Patient Group: At baseline, Day 1 of cycle 2 and beyond, after 6 months of chemotherapy, and at end of study visit.
Sponsors
Healios Oncology Nutrition
M.D. Anderson Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
17 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients who will be initiating therapy with any investigator-initiated mTOR inhibitor based therapy in the Department of Investigational Cancer Therapeutics (Phase I Program) or initiating radiation therapy to the esophagus. 2. For the esophagitis arm, any patient with thoracic malignancies, which will receive radiation alone or concurrent chemo/radiation. Radiation dose must be \>/= 45 Gy. For the esophagitis arm, induction chemotherapy is allowed. 3. Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to any study specific procedures. 4. Patients must be \>/= 17 years of age. 5. Females of childbearing potential must have a negative pregnancy test. Sexually active patients must agree to use contraception prior to, during, and 30 days after last dose.
Exclusion criteria
1\) Patients currently receiving therapy for mucositis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Severity of Esophagitis for Radiation Therapy Patients | 6 weeks | For esophagus radiation participants, the severity of esophagitis will be taken as the highest grade observed by week six. Wilcoxon rank sum test used to compare the ordered categories of esophagitis severity. |
| Severity of Oral Mucositis for mTOR Inhibitor Patients | 6 months after start of mTOR inhibitor based treatment | For mTOR inhibitor patients, the severity of oral mucositis will be taken as the maximum grade observed during the 6-month study period. Wilcoxon rank sum test used to compare the ordered categories of mucositis severity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quality of Life (QOL) in Esophagus Radiation Patients at Baseline | at baseline | The Quality of Life assessed by the MD Anderson Symptom Inventory for head and neck cancer (MDASI-HN). The 13 Core symptoms include dry mouth, fatigue, pain, disturbed sleep, drowsiness, feeling of being distressed, anorexia, sadness, numbness/tingling, dyspnea, difficulty remembering, nausea, and vomiting. The 9 Head and Neck symptoms include mouth sores, problems with taste, constipation, teeth/gum problems, skin pain, difficulty with voice, choking/coughing, difficulty swallowing, and problems with mucus specific to head and neck cancers. Total symptom severity include 24 core and Head and Neck symptoms together. Symptom interference asks patients about how their symptoms impact their daily functions. The severity of each symptom and symptom interference is rated on a numerical scale from 0 (symptom is absent) to 10 (worst possible severity). Higher scores indicate a greater symptom burden. |
| Quality of Life (QOL) in mTOR Inhibitor Patients at Baseline | at baseline | The Quality of Life assessed by the MD Anderson Symptom Inventory for head and neck cancer (MDASI-HN). The 13 Core symptoms include dry mouth, fatigue, pain, disturbed sleep, drowsiness, feeling of being distressed, anorexia, sadness, numbness/tingling, dyspnea, difficulty remembering, nausea, and vomiting. The 9 Head and Neck symptoms include mouth sores, problems with taste, constipation, teeth/gum problems, skin pain, difficulty with voice, choking/coughing, difficulty swallowing, and problems with mucus specific to head and neck cancers. Total symptom severity include 24 core and Head and Neck symptoms together. Symptom interference asks patients about how their symptoms impact their daily functions. The severity of each symptom and symptom interference is rated on a numerical scale from 0 (symptom is absent) to 10 (worst possible severity). Higher scores indicate a greater symptom burden. |
| Number of Participants With Esophagitis During 6 Weeks After Radiation Treatment Start | 6 weeks | Participants in each arm received at least 60% of planned doses of the study drug (glutamine or placebo). |
| Mucositis Incidence Per Participant During 6 Months After mTOR Inhibitor Treatment Start | 6 months | — |
| Grade 3 or Higher Esophagitis Incidence Per Participant During 6 Weeks After Radiation Start | 6 weeks | — |
| Grade 3 or Higher Mucositis Incidence Per Participant During 6 Months After Treatment Start | 6 month | — |
| Duration of Esophagitis After Radiation Treatment Start | From event starts to end of study visit | — |
| Duration of Mucositis After mTOR Inhibitor Treatment Start | From event starts to end of study visit | — |
| Time to Esophagitis on the Radiation Cohort Onset | From radiation starts to end of study visit | — |
| Proportion of Participants Who Were Mucositis-Free at 18.3 Weeks | 18.3 weeks | Proportion of participants who were free of Mucositis at 18.3 weeks.. |
| Number of Participants With Cancer Treatment Interruptions Due to Esophagitis | From radiation treatment start to end of study visit, approximately 6 months | — |
| Number of Participants With Cancer Treatment Interruptions Due to Mucositis | 6 months after start of mTOR inhibitor based treatment | — |
| Radiation Cohort Participant Weight Change From Baseline to End of Study | from baseline to 6 months post radiation therapy | Investigators recorded weight at baseline to the end of treatment with glutamine/placebo. Weight loss calculated at each study assessment visit using the Wilcoxon rank sum test. |
| mTOR Inhibitor Cohort Participant Weight Change From Baseline to End of Study | baseline, weekly during Cycle 1, and Day 1 of Cycle 2 and beyond, and 4 weeks and 6 months after the last dose of the mTOR inhibitor | Investigators recorded the weight at baseline and the end of the study. Weight loss calculated at each study assessment visit using the Wilcoxon rank sum test. |
| Summary of Adverse Events by Grade and Relationship - Radiation Cohort | weekly during radiation, 1 month and 6 months post radiation therapy until resolution, stabilization, death, loss to follow up, or commencement of new therapy | CTCAE version 4.03 used to access the adverse events. Grade 1 Asymptomatic; clinical or diagnostic observations only; intervention not indicated Grade 2 Symptomatic; altered eating/swallowing; oral supplements indicated Grade 3 Severely altered eating/swallowing; tube feeding, TPN or hospitalization indicated. Total toxicity-evaluable is the total number of participants who had at least one dose of glutamine or placebo. |
| Summary of Adverse Events by Grade and Relationship - mTOR Inhibitor Cohort | weekly during Cycle 1, and Day 1 of Cycle 2 and beyond, and 4 weeks and 6 months after the last dose of the mTOR inhibitor until resolution, stabilization, death, loss to follow up, or commencement of new therapy | CTCAE version 4.03 used to access the adverse events. Grade 1 Asymptomatic; clinical or diagnostic observations only; intervention not indicated Grade 2 Symptomatic; altered eating/swallowing; oral supplements indicated Grade 3 Severely altered eating/swallowing; tube feeding, TPN or hospitalization indicated. Total toxicity-evaluable is the total number of participants who had at least one dose of glutamine or placebo |
Countries
United States
Participant flow
Pre-assignment details
The mTOR inhibitor cohort 24 patients consented. 10 enrolled patients became ineligible after consent and before randomization due to changes in their treatment plan. The radiation cohort enrolled 53 patients; 27 were randomized to the glutamine arm and 26 were randomized to the placebo arm.
Participants by arm
| Arm | Count |
|---|---|
| Radiation Therapy to Esophagus Patient Group - Glutamine Glutamine taken as a sugary drink by mouth. Participant will take the drink twice daily starting first day radiation therapy to the esophagus received. Participant to swallow the drink in small amounts several times.
Questionnaire completion for Radiation Therapy to Esophagus Patient Group: At baseline, Week 3, 4, 5, and 7 of radiation, and at end of study visit. | 27 |
| Radiation Therapy to Esophagus Patient Group - Placebo Placebo taken as a sugary drink by mouth. Participant will take the drink twice daily starting first day radiation therapy to the esophagus received. Participant to swallow the drink in small amounts several times.
Questionnaire completion for Radiation Therapy to Esophagus Patient Group: At baseline, Week 3, 4, 5, and 7 of radiation, and at end of study visit. | 26 |
| mTOR Inhibitor Patient Group - Glutamine Glutamine taken as a sugary drink by mouth. Participant will take the drink twice daily starting first day anti-cancer therapy received. Participant to swish the drink for 10 seconds and swallow. Four weeks of treatment constitute 1 cycle for participants on mTOR inhibitor therapy.
Questionnaires: Questionnaire completion for mTOR Inhibitor Patient Group: At baseline, Day 1 of cycle 2 and beyond, after 6 months of chemotherapy, and at end of study visit. | 7 |
| mTOR Inhibitor Patient Group - Placebo Participants receive placebo beginning on Day 1 of an mTOR inhibitor based therapy. Placebo taken as a sugary drink by mouth. Participant will take the drink twice daily starting first day anti-cancer therapy received. Participant to swish the drink for 10 seconds and swallow. Four weeks of treatment constitute 1 cycle for participants on mTOR inhibitor therapy.
Questionnaire completion for mTOR Inhibitor Patient Group: At baseline, Day 1 of cycle 2 and beyond, after 6 months of chemotherapy, and at end of study visit. | 6 |
| Total | 66 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Ineligible | 1 | 0 | 0 | 0 |
| Overall Study | Lack of Insurance Coverage | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | mTOR Inhibitor Patient Group - Glutamine | Total | Radiation Therapy to Esophagus Patient Group - Glutamine | mTOR Inhibitor Patient Group - Placebo | Radiation Therapy to Esophagus Patient Group - Placebo |
|---|---|---|---|---|---|
| Age, Continuous | 64.3 years STANDARD_DEVIATION 10.5 | 65.8 years STANDARD_DEVIATION 11 | 67.6 years STANDARD_DEVIATION 9.8 | 60.3 years STANDARD_DEVIATION 13.4 | 64.9 years STANDARD_DEVIATION 11.8 |
| BMI | — | 27.6 kg/m^2 STANDARD_DEVIATION 4.9 | 27.0 kg/m^2 STANDARD_DEVIATION 5.1 | — | 28.2 kg/m^2 STANDARD_DEVIATION 4.7 |
| Cancer Type Endometrial cancer | 7 Participants | 13 Participants | 0 Participants | 6 Participants | 0 Participants |
| Cancer Type Esophageal | 0 Participants | 6 Participants | 2 Participants | 0 Participants | 4 Participants |
| Cancer Type Head & Neck | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Cancer Type Lung | 0 Participants | 45 Participants | 23 Participants | 0 Participants | 22 Participants |
| Cancer Type Sarcoma | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 10 Participants | 1 Participants | 1 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 56 Participants | 26 Participants | 5 Participants | 20 Participants |
| Region of Enrollment United States | 7 participants | 66 participants | 27 participants | 6 participants | 26 participants |
| Sex: Female, Male Female | 7 Participants | 35 Participants | 13 Participants | 6 Participants | 9 Participants |
| Sex: Female, Male Male | 0 Participants | 31 Participants | 14 Participants | 0 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 6 / 25 | 2 / 24 | 0 / 7 | 0 / 6 |
| other Total, other adverse events | 20 / 25 | 15 / 24 | 5 / 7 | 6 / 6 |
| serious Total, serious adverse events | 5 / 25 | 3 / 24 | 1 / 7 | 2 / 6 |
Outcome results
Primary
Severity of Esophagitis for Radiation Therapy Patients
For esophagus radiation participants, the severity of esophagitis will be taken as the highest grade observed by week six. Wilcoxon rank sum test used to compare the ordered categories of esophagitis severity.
Time frame: 6 weeks
Population: Participants who took at least 60% of the planned doses of the study treatment and were evaluable per protocol definition.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Radiation Therapy to Esophagus Patient Group - Glutamine | Severity of Esophagitis for Radiation Therapy Patients | Grade 1 | 2 Participants |
| Radiation Therapy to Esophagus Patient Group - Glutamine | Severity of Esophagitis for Radiation Therapy Patients | Grade 2 | 5 Participants |
| Radiation Therapy to Esophagus Patient Group - Glutamine | Severity of Esophagitis for Radiation Therapy Patients | Grade 3 | 7 Participants |
| Radiation Therapy to Esophagus Patient Group - Glutamine | Severity of Esophagitis for Radiation Therapy Patients | Absent | 5 Participants |
| Radiation Therapy to Esophagus Patient Group - Placebo | Severity of Esophagitis for Radiation Therapy Patients | Absent | 6 Participants |
| Radiation Therapy to Esophagus Patient Group - Placebo | Severity of Esophagitis for Radiation Therapy Patients | Grade 1 | 0 Participants |
| Radiation Therapy to Esophagus Patient Group - Placebo | Severity of Esophagitis for Radiation Therapy Patients | Grade 3 | 5 Participants |
| Radiation Therapy to Esophagus Patient Group - Placebo | Severity of Esophagitis for Radiation Therapy Patients | Grade 2 | 8 Participants |
p-value: 0.73Wilcoxon (Mann-Whitney)
Primary
Severity of Oral Mucositis for mTOR Inhibitor Patients
For mTOR inhibitor patients, the severity of oral mucositis will be taken as the maximum grade observed during the 6-month study period. Wilcoxon rank sum test used to compare the ordered categories of mucositis severity.
Time frame: 6 months after start of mTOR inhibitor based treatment
Population: Evaluable Participants in the mTOR Inhibitor Cohort
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Radiation Therapy to Esophagus Patient Group - Glutamine | Severity of Oral Mucositis for mTOR Inhibitor Patients | Grade 1 | 1 Participants |
| Radiation Therapy to Esophagus Patient Group - Glutamine | Severity of Oral Mucositis for mTOR Inhibitor Patients | Grade 2 | 0 Participants |
| Radiation Therapy to Esophagus Patient Group - Glutamine | Severity of Oral Mucositis for mTOR Inhibitor Patients | Grade 3 | 1 Participants |
| Radiation Therapy to Esophagus Patient Group - Glutamine | Severity of Oral Mucositis for mTOR Inhibitor Patients | Absent | 5 Participants |
| Radiation Therapy to Esophagus Patient Group - Placebo | Severity of Oral Mucositis for mTOR Inhibitor Patients | Absent | 3 Participants |
| Radiation Therapy to Esophagus Patient Group - Placebo | Severity of Oral Mucositis for mTOR Inhibitor Patients | Grade 1 | 3 Participants |
| Radiation Therapy to Esophagus Patient Group - Placebo | Severity of Oral Mucositis for mTOR Inhibitor Patients | Grade 3 | 0 Participants |
| Radiation Therapy to Esophagus Patient Group - Placebo | Severity of Oral Mucositis for mTOR Inhibitor Patients | Grade 2 | 0 Participants |
p-value: 0.68Wilcoxon (Mann-Whitney)
Secondary
Duration of Esophagitis After Radiation Treatment Start
Time frame: From event starts to end of study visit
Population: Participants in the radiation cohort who experienced esophagitis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Radiation Therapy to Esophagus Patient Group - Glutamine | Duration of Esophagitis After Radiation Treatment Start | 6.3 weeks |
| Radiation Therapy to Esophagus Patient Group - Placebo | Duration of Esophagitis After Radiation Treatment Start | 7.1 weeks |
p-value: 0.54Wilcoxon (Mann-Whitney)
Secondary
Duration of Mucositis After mTOR Inhibitor Treatment Start
Time frame: From event starts to end of study visit
Population: Participants in the mTOR cohort who experienced mucositis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Radiation Therapy to Esophagus Patient Group - Glutamine | Duration of Mucositis After mTOR Inhibitor Treatment Start | 10.9 weeks |
| Radiation Therapy to Esophagus Patient Group - Placebo | Duration of Mucositis After mTOR Inhibitor Treatment Start | 9.0 weeks |
p-value: 1Wilcoxon (Mann-Whitney)
Secondary
Grade 3 or Higher Esophagitis Incidence Per Participant During 6 Weeks After Radiation Start
Time frame: 6 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Radiation Therapy to Esophagus Patient Group - Glutamine | Grade 3 or Higher Esophagitis Incidence Per Participant During 6 Weeks After Radiation Start | Absent, Grade 1 or 2 | 12 Participants |
| Radiation Therapy to Esophagus Patient Group - Glutamine | Grade 3 or Higher Esophagitis Incidence Per Participant During 6 Weeks After Radiation Start | Grade 3 | 7 Participants |
| Radiation Therapy to Esophagus Patient Group - Placebo | Grade 3 or Higher Esophagitis Incidence Per Participant During 6 Weeks After Radiation Start | Absent, Grade 1 or 2 | 14 Participants |
| Radiation Therapy to Esophagus Patient Group - Placebo | Grade 3 or Higher Esophagitis Incidence Per Participant During 6 Weeks After Radiation Start | Grade 3 | 5 Participants |
p-value: 0.73Fisher Exact
Secondary
Grade 3 or Higher Mucositis Incidence Per Participant During 6 Months After Treatment Start
Time frame: 6 month
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Radiation Therapy to Esophagus Patient Group - Glutamine | Grade 3 or Higher Mucositis Incidence Per Participant During 6 Months After Treatment Start | Absent, Grade 1 or 2 | 6 Participants |
| Radiation Therapy to Esophagus Patient Group - Glutamine | Grade 3 or Higher Mucositis Incidence Per Participant During 6 Months After Treatment Start | Grade 3 | 1 Participants |
| Radiation Therapy to Esophagus Patient Group - Placebo | Grade 3 or Higher Mucositis Incidence Per Participant During 6 Months After Treatment Start | Absent, Grade 1 or 2 | 6 Participants |
| Radiation Therapy to Esophagus Patient Group - Placebo | Grade 3 or Higher Mucositis Incidence Per Participant During 6 Months After Treatment Start | Grade 3 | 0 Participants |
p-value: 1Fisher Exact
Secondary
mTOR Inhibitor Cohort Participant Weight Change From Baseline to End of Study
Investigators recorded the weight at baseline and the end of the study. Weight loss calculated at each study assessment visit using the Wilcoxon rank sum test.
Time frame: baseline, weekly during Cycle 1, and Day 1 of Cycle 2 and beyond, and 4 weeks and 6 months after the last dose of the mTOR inhibitor
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Radiation Therapy to Esophagus Patient Group - Glutamine | mTOR Inhibitor Cohort Participant Weight Change From Baseline to End of Study | -5.4 kg |
| Radiation Therapy to Esophagus Patient Group - Placebo | mTOR Inhibitor Cohort Participant Weight Change From Baseline to End of Study | -4.3 kg |
p-value: 0.39Wilcoxon (Mann-Whitney)
Secondary
Mucositis Incidence Per Participant During 6 Months After mTOR Inhibitor Treatment Start
Time frame: 6 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Radiation Therapy to Esophagus Patient Group - Glutamine | Mucositis Incidence Per Participant During 6 Months After mTOR Inhibitor Treatment Start | None | 5 Participants |
| Radiation Therapy to Esophagus Patient Group - Glutamine | Mucositis Incidence Per Participant During 6 Months After mTOR Inhibitor Treatment Start | Mucositis | 2 Participants |
| Radiation Therapy to Esophagus Patient Group - Placebo | Mucositis Incidence Per Participant During 6 Months After mTOR Inhibitor Treatment Start | None | 3 Participants |
| Radiation Therapy to Esophagus Patient Group - Placebo | Mucositis Incidence Per Participant During 6 Months After mTOR Inhibitor Treatment Start | Mucositis | 3 Participants |
p-value: 0.59Fisher Exact
Secondary
Number of Participants With Cancer Treatment Interruptions Due to Esophagitis
Time frame: From radiation treatment start to end of study visit, approximately 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Radiation Therapy to Esophagus Patient Group - Glutamine | Number of Participants With Cancer Treatment Interruptions Due to Esophagitis | 0 Participants |
| Radiation Therapy to Esophagus Patient Group - Placebo | Number of Participants With Cancer Treatment Interruptions Due to Esophagitis | 0 Participants |
Secondary
Number of Participants With Cancer Treatment Interruptions Due to Mucositis
Time frame: 6 months after start of mTOR inhibitor based treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Radiation Therapy to Esophagus Patient Group - Glutamine | Number of Participants With Cancer Treatment Interruptions Due to Mucositis | 0 Participants |
| Radiation Therapy to Esophagus Patient Group - Placebo | Number of Participants With Cancer Treatment Interruptions Due to Mucositis | 0 Participants |
Secondary
Number of Participants With Esophagitis During 6 Weeks After Radiation Treatment Start
Participants in each arm received at least 60% of planned doses of the study drug (glutamine or placebo).
Time frame: 6 weeks
Population: Evaluable participant
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Radiation Therapy to Esophagus Patient Group - Glutamine | Number of Participants With Esophagitis During 6 Weeks After Radiation Treatment Start | None | 5 Participants |
| Radiation Therapy to Esophagus Patient Group - Glutamine | Number of Participants With Esophagitis During 6 Weeks After Radiation Treatment Start | Esophagitis | 14 Participants |
| Radiation Therapy to Esophagus Patient Group - Placebo | Number of Participants With Esophagitis During 6 Weeks After Radiation Treatment Start | None | 6 Participants |
| Radiation Therapy to Esophagus Patient Group - Placebo | Number of Participants With Esophagitis During 6 Weeks After Radiation Treatment Start | Esophagitis | 13 Participants |
p-value: 1Fisher Exact
Secondary
Proportion of Participants Who Were Mucositis-Free at 18.3 Weeks
Proportion of participants who were free of Mucositis at 18.3 weeks..
Time frame: 18.3 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Radiation Therapy to Esophagus Patient Group - Glutamine | Proportion of Participants Who Were Mucositis-Free at 18.3 Weeks | 71 percentage of participants |
| Radiation Therapy to Esophagus Patient Group - Placebo | Proportion of Participants Who Were Mucositis-Free at 18.3 Weeks | 33 percentage of participants |
Secondary
Quality of Life (QOL) in Esophagus Radiation Patients at Baseline
The Quality of Life assessed by the MD Anderson Symptom Inventory for head and neck cancer (MDASI-HN). The 13 Core symptoms include dry mouth, fatigue, pain, disturbed sleep, drowsiness, feeling of being distressed, anorexia, sadness, numbness/tingling, dyspnea, difficulty remembering, nausea, and vomiting. The 9 Head and Neck symptoms include mouth sores, problems with taste, constipation, teeth/gum problems, skin pain, difficulty with voice, choking/coughing, difficulty swallowing, and problems with mucus specific to head and neck cancers. Total symptom severity include 24 core and Head and Neck symptoms together. Symptom interference asks patients about how their symptoms impact their daily functions. The severity of each symptom and symptom interference is rated on a numerical scale from 0 (symptom is absent) to 10 (worst possible severity). Higher scores indicate a greater symptom burden.
Time frame: at baseline
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Radiation Therapy to Esophagus Patient Group - Glutamine | Quality of Life (QOL) in Esophagus Radiation Patients at Baseline | Total Symptom Severity | 1.0 score on a scale |
| Radiation Therapy to Esophagus Patient Group - Glutamine | Quality of Life (QOL) in Esophagus Radiation Patients at Baseline | Core Symptom Severity | 1.4 score on a scale |
| Radiation Therapy to Esophagus Patient Group - Glutamine | Quality of Life (QOL) in Esophagus Radiation Patients at Baseline | Head & Neck symptom Severity | 0.4 score on a scale |
| Radiation Therapy to Esophagus Patient Group - Glutamine | Quality of Life (QOL) in Esophagus Radiation Patients at Baseline | Symptom Interference Severity | 0.5 score on a scale |
| Radiation Therapy to Esophagus Patient Group - Placebo | Quality of Life (QOL) in Esophagus Radiation Patients at Baseline | Symptom Interference Severity | 0.5 score on a scale |
| Radiation Therapy to Esophagus Patient Group - Placebo | Quality of Life (QOL) in Esophagus Radiation Patients at Baseline | Total Symptom Severity | 1.0 score on a scale |
| Radiation Therapy to Esophagus Patient Group - Placebo | Quality of Life (QOL) in Esophagus Radiation Patients at Baseline | Head & Neck symptom Severity | 0.6 score on a scale |
| Radiation Therapy to Esophagus Patient Group - Placebo | Quality of Life (QOL) in Esophagus Radiation Patients at Baseline | Core Symptom Severity | 1.3 score on a scale |
Secondary
Quality of Life (QOL) in mTOR Inhibitor Patients at Baseline
The Quality of Life assessed by the MD Anderson Symptom Inventory for head and neck cancer (MDASI-HN). The 13 Core symptoms include dry mouth, fatigue, pain, disturbed sleep, drowsiness, feeling of being distressed, anorexia, sadness, numbness/tingling, dyspnea, difficulty remembering, nausea, and vomiting. The 9 Head and Neck symptoms include mouth sores, problems with taste, constipation, teeth/gum problems, skin pain, difficulty with voice, choking/coughing, difficulty swallowing, and problems with mucus specific to head and neck cancers. Total symptom severity include 24 core and Head and Neck symptoms together. Symptom interference asks patients about how their symptoms impact their daily functions. The severity of each symptom and symptom interference is rated on a numerical scale from 0 (symptom is absent) to 10 (worst possible severity). Higher scores indicate a greater symptom burden.
Time frame: at baseline
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Radiation Therapy to Esophagus Patient Group - Glutamine | Quality of Life (QOL) in mTOR Inhibitor Patients at Baseline | Total Symptom severity | 1.0 score on a scale |
| Radiation Therapy to Esophagus Patient Group - Glutamine | Quality of Life (QOL) in mTOR Inhibitor Patients at Baseline | Core Symptom severity | 1.3 score on a scale |
| Radiation Therapy to Esophagus Patient Group - Glutamine | Quality of Life (QOL) in mTOR Inhibitor Patients at Baseline | Head & Neck symptom severity | 0.4 score on a scale |
| Radiation Therapy to Esophagus Patient Group - Glutamine | Quality of Life (QOL) in mTOR Inhibitor Patients at Baseline | Symptom Interference severity | 0.3 score on a scale |
| Radiation Therapy to Esophagus Patient Group - Placebo | Quality of Life (QOL) in mTOR Inhibitor Patients at Baseline | Symptom Interference severity | 0.9 score on a scale |
| Radiation Therapy to Esophagus Patient Group - Placebo | Quality of Life (QOL) in mTOR Inhibitor Patients at Baseline | Total Symptom severity | 1.0 score on a scale |
| Radiation Therapy to Esophagus Patient Group - Placebo | Quality of Life (QOL) in mTOR Inhibitor Patients at Baseline | Head & Neck symptom severity | 0.3 score on a scale |
| Radiation Therapy to Esophagus Patient Group - Placebo | Quality of Life (QOL) in mTOR Inhibitor Patients at Baseline | Core Symptom severity | 1.5 score on a scale |
Secondary
Radiation Cohort Participant Weight Change From Baseline to End of Study
Investigators recorded weight at baseline to the end of treatment with glutamine/placebo. Weight loss calculated at each study assessment visit using the Wilcoxon rank sum test.
Time frame: from baseline to 6 months post radiation therapy
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Radiation Therapy to Esophagus Patient Group - Glutamine | Radiation Cohort Participant Weight Change From Baseline to End of Study | -0.9 kg |
| Radiation Therapy to Esophagus Patient Group - Placebo | Radiation Cohort Participant Weight Change From Baseline to End of Study | -2.8 kg |
p-value: 0.83Wilcoxon (Mann-Whitney)
Secondary
Summary of Adverse Events by Grade and Relationship - mTOR Inhibitor Cohort
CTCAE version 4.03 used to access the adverse events. Grade 1 Asymptomatic; clinical or diagnostic observations only; intervention not indicated Grade 2 Symptomatic; altered eating/swallowing; oral supplements indicated Grade 3 Severely altered eating/swallowing; tube feeding, TPN or hospitalization indicated. Total toxicity-evaluable is the total number of participants who had at least one dose of glutamine or placebo
Time frame: weekly during Cycle 1, and Day 1 of Cycle 2 and beyond, and 4 weeks and 6 months after the last dose of the mTOR inhibitor until resolution, stabilization, death, loss to follow up, or commencement of new therapy
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Radiation Therapy to Esophagus Patient Group - Glutamine | Summary of Adverse Events by Grade and Relationship - mTOR Inhibitor Cohort | Grade 3 Unrelated | 3 adverse events |
| Radiation Therapy to Esophagus Patient Group - Glutamine | Summary of Adverse Events by Grade and Relationship - mTOR Inhibitor Cohort | Grade 2 Unrelated | 0 adverse events |
| Radiation Therapy to Esophagus Patient Group - Glutamine | Summary of Adverse Events by Grade and Relationship - mTOR Inhibitor Cohort | Grade 1 Unrelated | 6 adverse events |
| Radiation Therapy to Esophagus Patient Group - Placebo | Summary of Adverse Events by Grade and Relationship - mTOR Inhibitor Cohort | Grade 3 Unrelated | 3 adverse events |
| Radiation Therapy to Esophagus Patient Group - Placebo | Summary of Adverse Events by Grade and Relationship - mTOR Inhibitor Cohort | Grade 2 Unrelated | 2 adverse events |
| Radiation Therapy to Esophagus Patient Group - Placebo | Summary of Adverse Events by Grade and Relationship - mTOR Inhibitor Cohort | Grade 1 Unrelated | 6 adverse events |
Secondary
Summary of Adverse Events by Grade and Relationship - Radiation Cohort
CTCAE version 4.03 used to access the adverse events. Grade 1 Asymptomatic; clinical or diagnostic observations only; intervention not indicated Grade 2 Symptomatic; altered eating/swallowing; oral supplements indicated Grade 3 Severely altered eating/swallowing; tube feeding, TPN or hospitalization indicated. Total toxicity-evaluable is the total number of participants who had at least one dose of glutamine or placebo.
Time frame: weekly during radiation, 1 month and 6 months post radiation therapy until resolution, stabilization, death, loss to follow up, or commencement of new therapy
Population: Total toxicity-evaluable is the total number of participants who had at least one dose of glutamine or placebo.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Radiation Therapy to Esophagus Patient Group - Glutamine | Summary of Adverse Events by Grade and Relationship - Radiation Cohort | Grade 3 Unlikely Related | 1 adverse events |
| Radiation Therapy to Esophagus Patient Group - Glutamine | Summary of Adverse Events by Grade and Relationship - Radiation Cohort | Grade 3 Unrelated | 13 adverse events |
| Radiation Therapy to Esophagus Patient Group - Glutamine | Summary of Adverse Events by Grade and Relationship - Radiation Cohort | Grade 2 Possibly related | 2 adverse events |
| Radiation Therapy to Esophagus Patient Group - Glutamine | Summary of Adverse Events by Grade and Relationship - Radiation Cohort | Grade 2 Unlikely related | 0 adverse events |
| Radiation Therapy to Esophagus Patient Group - Glutamine | Summary of Adverse Events by Grade and Relationship - Radiation Cohort | Grade 2 Unrelated | 15 adverse events |
| Radiation Therapy to Esophagus Patient Group - Glutamine | Summary of Adverse Events by Grade and Relationship - Radiation Cohort | Grade 1 Possibly related | 3 adverse events |
| Radiation Therapy to Esophagus Patient Group - Glutamine | Summary of Adverse Events by Grade and Relationship - Radiation Cohort | Grade 1 Unlikely related | 1 adverse events |
| Radiation Therapy to Esophagus Patient Group - Glutamine | Summary of Adverse Events by Grade and Relationship - Radiation Cohort | Grade 1 Unrelated | 7 adverse events |
| Radiation Therapy to Esophagus Patient Group - Placebo | Summary of Adverse Events by Grade and Relationship - Radiation Cohort | Grade 1 Unrelated | 0 adverse events |
| Radiation Therapy to Esophagus Patient Group - Placebo | Summary of Adverse Events by Grade and Relationship - Radiation Cohort | Grade 3 Unlikely Related | 0 adverse events |
| Radiation Therapy to Esophagus Patient Group - Placebo | Summary of Adverse Events by Grade and Relationship - Radiation Cohort | Grade 2 Unrelated | 15 adverse events |
| Radiation Therapy to Esophagus Patient Group - Placebo | Summary of Adverse Events by Grade and Relationship - Radiation Cohort | Grade 3 Unrelated | 11 adverse events |
| Radiation Therapy to Esophagus Patient Group - Placebo | Summary of Adverse Events by Grade and Relationship - Radiation Cohort | Grade 1 Unlikely related | 0 adverse events |
| Radiation Therapy to Esophagus Patient Group - Placebo | Summary of Adverse Events by Grade and Relationship - Radiation Cohort | Grade 2 Possibly related | 1 adverse events |
| Radiation Therapy to Esophagus Patient Group - Placebo | Summary of Adverse Events by Grade and Relationship - Radiation Cohort | Grade 1 Possibly related | 0 adverse events |
| Radiation Therapy to Esophagus Patient Group - Placebo | Summary of Adverse Events by Grade and Relationship - Radiation Cohort | Grade 2 Unlikely related | 0 adverse events |
Secondary
Time to Esophagitis on the Radiation Cohort Onset
Time frame: From radiation starts to end of study visit
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Radiation Therapy to Esophagus Patient Group - Glutamine | Time to Esophagitis on the Radiation Cohort Onset | 2.9 weeks |
| Radiation Therapy to Esophagus Patient Group - Placebo | Time to Esophagitis on the Radiation Cohort Onset | 4.1 weeks |
p-value: 0.57Log Rank