NCT03839940: MIST

Dexamethasone in Reducing Everolimus-Induced Oral Stomatitis in Patients With Cancer

Terminated Phase 3 Results posted Last updated 29 January 2025

What this trial tests

Phase 3 trial testing Dexamethasone in Malignant Neoplasm in 39 participants. Terminated before completion.

Timeline

3 June 2019

Primary endpoint
8 January 2021

3 August 2022

Quick facts

Lead sponsor	Alliance for Clinical Trials in Oncology
Phase	Phase 3
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	supportive care
Enrollment	39
Start date	3 June 2019
Primary completion	8 January 2021
Estimated completion	3 August 2022
Sites	319 locations across United States

Drugs / interventions tested

• Dexamethasone (dexamethasone) — full drug profile →
• Placebo
• Questionnaire
• Quality-of-Life Assessment
• Everolimus (everolimus) — full drug profile →

Conditions studied

• Malignant Neoplasm — all drugs for Malignant Neoplasm →

Sponsor

Alliance for Clinical Trials in Oncology

Who can join

18 and older, any sex, with Malignant Neoplasm. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Incidence Rate of the mTOR Inhibitor-associated Stomatitis (mIAS)-Related Pain Based on Daily Self-reports Via the Numerical Analogue Scale Primary · Up to 8 weeks

The numerical analogue mouth pain score (NAMPS) is a single item measured on a 0 to 10 scale, with 0 corresponding to "No pain" and 10 corresponding to "Pain as bad as it can be." Will compare the incidence rate of any mouth pain (i.e., any score greater than 0) as assessed by the NAMPS between the prevention versus early treatment approaches using a Chi-square test.

Group	Value	95% CI
Group I (Dexamethasone)	7
Group II (Placebo)	8
Group I (Dexamethasone)	9
Group II (Placebo)	9

Severity of Mouth Pain Scores Primary · Up to 8 weeks

Average Area Under the Curve per assessment (aAUCpa) of mouth pain scores as measured by NAMPS will be computed for each patient to summarize the sequence of numerical analogue mouth pain scores over the eight week study period. Scores are reported on a 0-100 scale, where 100 = better outcome QOL (i.e. less pain). The aAUCpa is the average of each AUC between each sequential assessment from treatment-initiation to the end of the treatment at 8 weeks post-treatment-initiation and will be compared between the two treatment arms.

Group	Value	95% CI
Group I (Dexamethasone)	11.3	± 14.83
Group II (Placebo)	4.6	± 6.86

Incidence Rate of the mTOR Inhibitor-associated Stomatitis (mIAS)-Related Pain Based on Daily Self-reports Via the Numerical Analogue Scale by Sex Secondary · Up to 8 weeks

NIH-required analysis. The numerical analogue mouth pain score (NAMPS) is a single item measured on a 0 to 10 scale, with 0 corresponding to "No pain" and 10 corresponding to "Pain as bad as it can be." Will compare the incidence rate of any mouth pain (i.e., any score greater than 0) as assessed by the NAMPS between the prevention versus early treatment approaches using a Chi-square test.

Female

Group	Value	95% CI
Group I (Dexamethasone)	5
Group II (Placebo)	8
Group I (Dexamethasone)	7
Group II (Placebo)	7

Male

Group	Value	95% CI
Group I (Dexamethasone)	2
Group II (Placebo)	0
Group I (Dexamethasone)	2
Group II (Placebo)	2

Incidence Rate of the mTOR Inhibitor-associated Stomatitis (mIAS)-Related Pain Based on Daily Self-reports Via the Numerical Analogue Scale by Race Secondary · Up to 8 weeks

NIH-required analysis. The numerical analogue mouth pain score (NAMPS) is a single item measured on a 0 to 10 scale, with 0 corresponding to "No pain" and 10 corresponding to "Pain as bad as it can be." Will compare the incidence rate of any mouth pain (i.e., any score greater than 0) as assessed by the NAMPS between the prevention versus early treatment approaches using a Chi-square test.

Black or African American

Group	Value	95% CI
Group I (Dexamethasone)	1
Group II (Placebo)	0
Group I (Dexamethasone)	3
Group II (Placebo)	1

White

Group	Value	95% CI
Group I (Dexamethasone)	6
Group II (Placebo)	8
Group I (Dexamethasone)	6
Group II (Placebo)	8

Incidence Rate of the mTOR Inhibitor-associated Stomatitis (mIAS)-Related Pain Based on Daily Self-reports Via the Numerical Analogue Scale by Ethnicity. Secondary · Up to 8 weeks

NIH-required analysis. The numerical analogue mouth pain score (NAMPS) is a single item measured on a 0 to 10 scale, with 0 corresponding to "No pain" and 10 corresponding to "Pain as bad as it can be." Will compare the incidence rate of any mouth pain (i.e., any score greater than 0) as assessed by the NAMPS between the prevention versus early treatment approaches using a Chi-square test.

Not Hispanic or Latino

Group	Value	95% CI
Group I (Dexamethasone)	6
Group II (Placebo)	7
Group I (Dexamethasone)	9
Group II (Placebo)	9

Other

Group	Value	95% CI
Group I (Dexamethasone)	1
Group II (Placebo)	1
Group I (Dexamethasone)	0
Group II (Placebo)	0

Severity of Mouth Pain Scores by Sex Secondary · Up to 8 weeks

Average Area Under the Curve per assessment (aAUCpa) of mouth pain scores as measured by NAMPS will be computed for each patient to summarize the sequence of numerical analogue mouth pain scores over the eight week study period. Scores are reported on a 0-100 scale, where 100 = better outcome QOL (i.e. less pain). The aAUCpa is the average of each AUC between each sequential assessment from treatment-initiation to the end of the treatment at 8 weeks post-treatment-initiation and will be compared between the two treatment arms.

Female

Group	Value	95% CI
Group I (Dexamethasone)	11.4	0.0 – 47.3
Group II (Placebo)	2.7	0.0 – 15.7

Male

Group	Value	95% CI
Group I (Dexamethasone)	11.0	0.0 – 33.4
Group II (Placebo)	18.8	17.0 – 20.7

Severity of Mouth Pain Scores by Race Secondary · Up to 8 weeks

Average Area Under the Curve per assessment (aAUCpa) of mouth pain scores as measured by NAMPS will be computed for each patient to summarize the sequence of numerical analogue mouth pain scores over the eight week study period. Scores are reported on a 0-100 scale, where 100 = better outcome QOL (i.e. less pain). The aAUCpa is the average of each AUC between each sequential assessment from treatment-initiation to the end of the treatment at 8 weeks post-treatment-initiation and will be compared between the two treatment arms.

Black or African American

Group	Value	95% CI
Group I (Dexamethasone)	9.3	0.0 – 22.8
Group II (Placebo)	7.9	7.9 – 7.9

White

Group	Value	95% CI
Group I (Dexamethasone)	12.0	0.0 – 47.3
Group II (Placebo)	4.4	0.0 – 20.7

Severity of Mouth Pain Scores by Ethnicity Secondary · Up to 8 weeks

Average Area Under the Curve per assessment (aAUCpa) of mouth pain scores as measured by NAMPS will be computed for each patient to summarize the sequence of numerical analogue mouth pain scores over the eight week study period. Scores are reported on a 0-100 scale, where 100 = better outcome QOL (i.e. less pain). The aAUCpa is the average of each AUC between each sequential assessment from treatment-initiation to the end of the treatment at 8 weeks post-treatment-initiation and will be compared between the two treatment arms.

Not Hispanic or Latino

Group	Value	95% CI
Group I (Dexamethasone)	12.1	0.0 – 47.3
Group II (Placebo)	4.9	0.0 – 20.7

Other

Group	Value	95% CI
Group I (Dexamethasone)	0.0	0.0 – 0.0
Group II (Placebo)	0.0	0.0 – 0.0

Adverse events — posted to ClinicalTrials.gov

Time frame: 8 weeks. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Group II (Placebo)

Serious: 3/18 (17%)

Deaths: 0/19

Group I (Dexamethasone)

Serious: 2/17 (12%)

Deaths: 0/20

Serious adverse events (10 terms)

Reaction	System	Group II (Placebo)	Group I (Dexamethasone)
Sinus tachycardia	Cardiac disorders	—	—
Lower gastrointestinal hemorrhage	Gastrointestinal disorders	—	—
Edema limbs	General disorders	—	—
Enterocolitis infectious	Infections and infestations	—	—
Creatinine increased	Investigations	—	—
Dehydration	Metabolism and nutrition disorders	—	—
Hyponatremia	Metabolism and nutrition disorders	—	—
Tumor pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Pneumonitis	Respiratory, thoracic and mediastinal disorders	—	—

Other adverse events (34 terms — click to expand)

Reaction	System	Group II (Placebo)	Group I (Dexamethasone)
Fatigue	General disorders	—	—
Insomnia	Psychiatric disorders	—	—
Mucositis oral	Gastrointestinal disorders	—	—
Oral pain	Gastrointestinal disorders	—	—
Hyperglycemia	Metabolism and nutrition disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Anorexia	Metabolism and nutrition disorders	—	—
Irritability	Psychiatric disorders	—	—
Diarrhea	Gastrointestinal disorders	—	—
Dry mouth	Gastrointestinal disorders	—	—
Mucosal infection	Infections and infestations	—	—
Alanine aminotransferase increased	Investigations	—	—
Aspartate aminotransferase increased	Investigations	—	—
Dysgeusia	Nervous system disorders	—	—
Anemia	Blood and lymphatic system disorders	—	—
Blood and lymph sys disorders - Oth Spec	Blood and lymphatic system disorders	—	—
Colitis	Gastrointestinal disorders	—	—
Gastrointestinal disorders - Oth spec	Gastrointestinal disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Bruising	Injury, poisoning and procedural complications	—	—
Fracture	Injury, poisoning and procedural complications	—	—
Alkaline phosphatase increased	Investigations	—	—
Creatinine increased	Investigations	—	—
Platelet count decreased	Investigations	—	—
White blood cell decreased	Investigations	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Neck pain	Musculoskeletal and connective tissue disorders	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—
Peripheral sensory neuropathy	Nervous system disorders	—	—
Depression	Psychiatric disorders	—	—
Breast pain	Reproductive system and breast disorders	—	—
Productive cough	Respiratory, thoracic and mediastinal disorders	—	—
Rash acneiform	Skin and subcutaneous tissue disorders	—	—

Most-reported serious reactions: Sinus tachycardia, Lower gastrointestinal hemorrhage, Edema limbs, Enterocolitis infectious, Creatinine increased, Dehydration, Hyponatremia, Tumor pain.

Data from ClinicalTrials.gov NCT03839940 adverse events section.

Sponsor's own description

This phase III trial studies how well dexamethasone works in reducing everolimus-induced oral stomatitis in patients with cancer. Dexamethasone may help to reduce the everolimus-induced oral stomatitis so as to improve quality of life in cancer patients.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Oral Mucositis: An Update on Innate Immunity and New Interventional Targets.
   Chen C, Zhang Q, Yu W, Chang B, et al · · 2020 · cited 44× · PMID 32479139 · DOI 10.1177/0022034520925421
2. Dexamethasone to prevent everolimus-induced stomatitis (Alliance MIST Trial: A221701).
   Ruddy KJ, Zahrieh D, He J, Waechter B, et al · · 2023 · cited 4× · PMID 36693773 · DOI 10.1053/j.seminoncol.2023.01.001