Olanzapine for Managing Anorexia in Head and Neck Cancer Patients Undergoing Chemoradiation, MACRO Trial

NCT06995508 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: I 3757323NCI-2025-03335
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial compares the effect of adding olanzapine to standard of care symptom management for nausea to standard of care alone in managing an abnormal loss of the appetite for food (anorexia) in patients treated with chemoradiation therapy (CRT) for head and neck cancer. Patients undergoing CRT may experience treatment-related side effects, including pain, nausea, and a discomfort in the ability to speak, swallow and eat. These side effects have been shown to increase weight loss, opiate use and hospitalization. Olanzapine is a drug used to treat certain mental disorders. It is also being studied in the treatment of nausea and vomiting caused by some cancer treatments. It is a type of anti-psychotic and a type of monoamine antagonist. Adding olanzapine to standard of care symptom management to limit nausea may be more effective than standard of care alone in managing anorexia in head and neck cancer patients during CRT.

Conditions

Cancer-Associated Anorexia; Head and Neck Squamous Cell Carcinoma; Neck Squamous Cell Carcinoma of Unknown Primary

Outcome Measures

Primary Outcomes (1)

• Average change in weight

  Will be summarized by study arm using the mean and standard deviation. A two-sample t-test will be used. All test assumptions will be verified graphically, and transformations or non-parametric approaches will be considered, as appropriate.

  From baseline to patient lowest weight during chemoradiation therapy (CRT) treatment, assessed up to 5 weeks after last dose of study treatment

Secondary Outcomes (10)

• Proportion of patients with severe weight loss

  At baseline up to any time point during CRT treatment, assessed up to 5 weeks after last dose of study treatment

• Incidence of adverse events

  Up to 5 weeks after last dose of study treatment

• Change in quality of life (QOL) scores

  Baseline up to 5 weeks after last dose of study treatment

• Change in Quality of Life

  Up to 5 weeks after last dose of study treatment

• Changes in sleep

  Baseline up to 5 weeks after last dose of study treatment

Study Arms (2)

Arm I (standard of care)

ACTIVE COMPARATOR

Patients receive standard of care symptom management on study per the discretion of the treating institution.

Other: Best Practice; Other: Questionnaire Administration

Arm II (olanzapine, standard of care)

EXPERIMENTAL

Starting day 1 of CRT, patients receive olanzapine PO QD for up to 10 weeks after completion of CRT in the absence of disease progression or unacceptable toxicity. Patients also receive standard of care symptom management on study per the discretion of the treating institution.

Other: Best Practice; Drug: Olanzapine; Other: Questionnaire Administration

Interventions

Best Practice OTHER

Given standard of care symptom management

Also known as: standard of care, standard therapy

Arm I (standard of care); Arm II (olanzapine, standard of care)

Olanzapine DRUG

Given PO

Also known as: LY 170053, Zyprexa, Zyprexa Zydis

Arm II (olanzapine, standard of care)

Questionnaire Administration OTHER

Ancillary studies

Arm I (standard of care); Arm II (olanzapine, standard of care)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years old
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
• Diagnosed with biopsy-proven, squamous cell carcinoma of the head and neck, including squamous cell carcinoma of the neck with unknown primary site
• Eligible for curative-intent chemoradiation therapy of the head and neck
• Patients must be eligible for concurrent systemic therapy (preferably platinum based) as determined by the treating medical oncologist to undergo platinum-based chemotherapy
• Ability to swallow and retain oral medication
• Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• Participants must agree to avoid the following while taking Olanzapine while they are on study:
• Taking the drug Symbyax (which already contains olanzapine)
• Consuming alcohol
• Operating hazardous machinery, including automobiles, until you are reasonably certain that the study drug therapy does not have any bad effects on your mental and physical health
• Participant must understand the investigational nature of this study and sign an institutional review board approved written informed consent form prior to receiving any study related procedure

You may not qualify if:

• Eligible for palliative-intent radiation therapy only
• Patients with a feeding tube
• Regular systemic steroid use
• Atypical antipsychotic use
• Other dopamine receptor blockers routinely used as anti-emetics (eg. prochlorperazine/compazine and metoclopramide) are allowed to be prescribed as usual care on this study
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, diabetes or psychiatric illness/social situations that would limit compliance with study requirements
• Known hypersensitivity to olanzapine
• Pregnant or nursing female participants
• Known history of seizures
• Unwilling or unable to follow protocol requirements
• Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

RECRUITING

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Practice Guidelines as Topic; Standard of Care; Olanzapine

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Guidelines as Topic; Quality Assurance, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality Indicators, Health Care; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Anurag K Singh

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2025
• First Posted: May 29, 2025
• Study Start: December 24, 2025
• Primary Completion (Estimated): November 15, 2030
• Study Completion (Estimated): November 15, 2031
• Last Updated: February 17, 2026

Record last verified: 2026-02

Locations

US (1)