Clinical trial NCT01952847: Randomized Trial of Glutamine in Patients With Mucositis or Esophagitis
Official title: Randomized, Double Blinded Placebo-Controlled Study of Glutamine in Patients With Oral Mucositis on an mTOR Inhibitor-based Regimen or Esophagitis on a Regimen Receiving Radiation to the Esophagus
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Advanced Cancers
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
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: Healios Oncology Nutrition
First posted: 2013-09-30
Enrollment: 77
Sex: ALL
Minimum age (years): 17
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Severity of Esophagitis for Radiation Therapy Patients
timeFrame: 6 weeks
measure: Severity of Oral Mucositis for mTOR Inhibitor Patients
timeFrame: 6 months after start of mTOR inhibitor based treatment
Secondary outcomes:
measure: Quality of Life (QOL) in Esophagus Radiation Patients at Baseline
timeFrame: at baseline
measure: Quality of Life (QOL) in mTOR Inhibitor Patients at Baseline
timeFrame: at baseline
measure: Number of Participants With Esophagitis During 6 Weeks After Radiation Treatment Start
timeFrame: 6 weeks
measure: Mucositis Incidence Per Participant During 6 Months After mTOR Inhibitor Treatment Start
timeFrame: 6 months
measure: Grade 3 or Higher Esophagitis Incidence Per Participant During 6 Weeks After Radiation Start
timeFrame: 6 weeks
measure: Grade 3 or Higher Mucositis Incidence Per Participant During 6 Months After Treatment Start
timeFrame: 6 month
measure: Duration of Esophagitis After Radiation Treatment Start
timeFrame: From event starts to end of study visit
measure: Duration of Mucositis After mTOR Inhibitor Treatment Start
timeFrame: From event starts to end of study visit
measure: Time to Esophagitis on the Radiation Cohort Onset
timeFrame: From radiation starts to end of study visit
measure: Proportion of Participants Who Were Mucositis-Free at 18.3 Weeks
timeFrame: 18.3 weeks
measure: Number of Participants With Cancer Treatment Interruptions Due to Esophagitis
timeFrame: From radiation treatment start to end of study visit, approximately 6 months
measure: Number of Participants With Cancer Treatment Interruptions Due to Mucositis
timeFrame: 6 months after start of mTOR inhibitor based treatment
measure: Radiation Cohort Participant Weight Change From Baseline to End of Study
timeFrame: from baseline to 6 months post radiation therapy
measure: mTOR Inhibitor Cohort Participant Weight Change From Baseline to End of Study
timeFrame: 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
measure: Summary of Adverse Events by Grade and Relationship - Radiation Cohort
timeFrame: weekly during radiation, 1 month and 6 months post radiation therapy until resolution, stabilization, death, loss to follow up, or commencement of new therapy
measure: Summary of Adverse Events by Grade and Relationship - mTOR Inhibitor Cohort
timeFrame: 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
Other outcomes:
Locations:
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Aung Naing, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Alshawa A, Cadena AP, Stephen B, Reddy A, Mendoza TR, McQuinn L, Lawhorn K, Zarifa A, Bernhardt AM, Fessaheye S, Warneke CL, Chang JY, Naing A. Effects of glutamine for prevention of radiation-induced esophagitis: a double-blind placebo-controlled trial. Invest New Drugs. 2021 Aug;39(4):1113-1122. doi: 10.1007/s10637-021-01074-w. Epub 2021 Feb 13.