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Randomized Trial of Glutamine in Patients With Mucositis or Esophagitis

Phase 3
Terminated
Conditions
Advanced Cancers
Interventions
Other: Placebo
Behavioral: Questionnaires
Registration Number
NCT01952847
Lead Sponsor
M.D. Anderson Cancer Center
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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
77
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
mTOR Inhibitor Patient Group - PlaceboPlaceboParticipants 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.
mTOR Inhibitor Patient Group - PlaceboQuestionnairesParticipants 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.
mTOR Inhibitor Patient Group - GlutamineQuestionnairesGlutamine 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.
Radiation Therapy to Esophagus Patient Group - PlaceboPlaceboPlacebo 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.
Radiation Therapy to Esophagus Patient Group - PlaceboQuestionnairesPlacebo 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.
Radiation Therapy to Esophagus Patient Group - GlutamineQuestionnairesGlutamine 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.
mTOR Inhibitor Patient Group - GlutamineGlutamineGlutamine 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.
Radiation Therapy to Esophagus Patient Group - GlutamineGlutamineGlutamine 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.
Primary Outcome Measures
NameTimeMethod
Severity of Esophagitis for Radiation Therapy Patients6 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 Patients6 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 Outcome Measures
NameTimeMethod
Summary of Adverse Events by Grade and Relationship - Radiation Cohortweekly 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.

Duration of Esophagitis After Radiation Treatment StartFrom event starts to end of study visit
Quality of Life (QOL) in mTOR Inhibitor Patients at Baselineat 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.

Mucositis Incidence Per Participant During 6 Months After mTOR Inhibitor Treatment Start6 months
Grade 3 or Higher Mucositis Incidence Per Participant During 6 Months After Treatment Start6 month
Time to Esophagitis on the Radiation Cohort OnsetFrom radiation starts to end of study visit
Number of Participants With Esophagitis During 6 Weeks After Radiation Treatment Start6 weeks

Participants in each arm received at least 60% of planned doses of the study drug (glutamine or placebo).

Radiation Cohort Participant Weight Change From Baseline to End of Studyfrom 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.

Duration of Mucositis After mTOR Inhibitor Treatment StartFrom event starts to end of study visit
Proportion of Participants Who Were Mucositis-Free at 18.3 Weeks18.3 weeks

Proportion of participants who were free of Mucositis at 18.3 weeks..

mTOR Inhibitor Cohort Participant Weight Change From Baseline to End of Studybaseline, 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.

Quality of Life (QOL) in Esophagus Radiation Patients at Baselineat 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.

Grade 3 or Higher Esophagitis Incidence Per Participant During 6 Weeks After Radiation Start6 weeks
Number of Participants With Cancer Treatment Interruptions Due to EsophagitisFrom radiation treatment start to end of study visit, approximately 6 months
Number of Participants With Cancer Treatment Interruptions Due to Mucositis6 months after start of mTOR inhibitor based treatment
Summary of Adverse Events by Grade and Relationship - mTOR Inhibitor Cohortweekly 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

Trial Locations

Locations (1)

University of Texas MD Anderson Cancer Center

🇺🇸

Houston, Texas, United States

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