Cancer-Associated AnorexiaPhase 2NCT06995508
Olanzapine for Managing Anorexia in Head and Neck Cancer Patients Undergoing Chemoradiation, MACRO Trial
A Phase 2 study testing Best Practice, Olanzapine and Questionnaire Administration in people with Cancer-Associated Anorexia and Head and Neck Squamous Cell Carcinoma, run by Roswell Park Cancer Institute at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer-Associated Anorexia, Head and Neck Squamous Cell Carcinoma, Neck Squamous Cell Carcinoma of Unknown Primary
- What is being tested?
- Best Practice, Olanzapine and Questionnaire Administration
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Dec 2025to 15 Nov 2031
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Roswell Park Cancer Institute
Buffalo, New York, 14263
Anurag K. Singh, 716-845-1179, Anurag.Singh@RoswellPark.org
Anurag K. Singh
About this study
Official title: Managing Anorexia During Chemoradiation With Olanzapine (MACRO)
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.
Read the detailed description
PRIMARY OBJECTIVE:
- To assess the effect of adding olanzapine to standard symptom management on preventing weight loss during chemoradiation.
SECONDARY OBJECTIVES:
- To assess the effect of olanzapine on:
- Preventing severe weight loss;
- The rate of toxicities-unrelated, possibly- or probably- related to the symptom management regimen (regardless of causality)
II, Quality of Life (QOL) scores:
- With particular attention to nausea, vomiting, appetite, loss, swallowing, pain; and Special attention to sleep;
- Opiate use, hospitalization rate, feeding tube use, chemotherapy delays, and additional olanzapine prescriptions.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive standard of care symptom management on study per the discretion of the treating institution.
ARM II: 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.
After completion of study treatment, patients are followed up at 5 weeks.
- Conditions
- Cancer-Associated Anorexia, Head and Neck Squamous Cell Carcinoma, Neck Squamous Cell Carcinoma of Unknown Primary
- Being tested
- Best Practice, Olanzapine, Questionnaire Administration
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Best PracticeOther
Also called standard of care, standard therapy
Given standard of care symptom management
OlanzapineDrug
Also called LY 170053, Zyprexa, Zyprexa Zydis
Given PO
Questionnaire AdministrationOther
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Arm I (standard of care) | Active comparator | Patients receive standard of care symptom management on study per the discretion of the treating institution. Receives: 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. Receives: Other: Best Practice; Drug: Olanzapine; Other: Questionnaire Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Will be defined as >= 10% body weight loss. Will be summarized by study arm and compared by the Fisher exact test or chi-squared test as appropriate.
Measured: 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
Will be assessed using the Cancer Therapy Evaluation Program National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Will be summarized by attribution and grade using frequencies and relative frequencies. Differences in CTCAE rates (grade 2 or higher) will be compared between groups using the Fisher exact Test or chi-Squared test as appropriate.
Measured: Up to 5 weeks after last dose of study treatment
Change in quality of life (QOL) scores
Will be assessed using the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) . The Oral Mucositis Weekly Questionnaire-Head and Neck Cancer will be used to describe the short-term effects of radiation on QOL during treatment. Scores will be assessed by comparing the within-patient change. The treatment effect will be estimated with a generalized linear mixed model, describing the continuous EORTC quality of life outcomes as a function of a random patient effect, and fixed effects for treatment assignment, time, the stratification factor, the treatment assignment and the treatment/time interaction. The magnitude, direction and 95% confidence interval for the adjusted interaction term estimate will be used to describe the effect of olanzapine in improving different QOL domains. An interaction p-value < 0.05 will be considered statistically significant.
Measured: Baseline up to 5 weeks after last dose of study treatment
Change in Quality of Life
Will be assessed using the EORTC QLQ-H\&N43 module questionnaire. Mean change from
Measured: Up to 5 weeks after last dose of study treatment
Changes in sleep
Will be assessed using the Insomnia Severity Index (ISI) score and the ISI category. Differences between treatment arms for categorical or binary end points will be compared using the chi-square test or Fisher's exact test as appropriate. Differences between treatment arms for continuous variables will be compared using the Mann-Whitney U test. Differences between treatment arms for time-to-event end points will be compared using Kaplan-Meier estimates and the log-rank test.
Measured: Baseline up to 5 weeks after last dose of study treatment
Opiate use
Will be defined as proportion of patients requiring opiate prescription during CRT, time to first opiate in days, and total opiate use in morphine milligram equivalents. Differences between treatment arms for categorical or binary end points will be compared using the chi-square test or Fisher's exact test as appropriate. Differences between treatment arms for continuous variables will be compared using the Mann-Whitney U test. Differences between treatment arms for time-to-event end points will be compared using Kaplan-Meier estimates and the log-rank test.
Measured: Up to 5 weeks after last dose of study treatment
Hospitalization rate
Will be defined as proportion of patients requiring inpatient hospital admission for any reason during CRT. Differences between treatment arms for categorical or binary end points will be compared using the chi-square test or Fisher's exact test as appropriate. Differences between treatment arms for continuous variables will be compared using the Mann-Whitney U test. Differences between treatment arms for time-to-event end points will be compared using Kaplan-Meier estimates and the log-rank test.
Measured: Up to 5 weeks after last dose of study treatment
Feeding tube use
Will be defined as the proportion of patients requiring feeding tube insertion during CRT. Differences between treatment arms for categorical or binary end points will be compared using the chi-square test or Fisher's exact test as appropriate. Differences between treatment arms for continuous variables will be compared using the Mann-Whitney U test. Differences between treatment arms for time-to-event end points will be compared using Kaplan-Meier estimates and the log-rank test.
Measured: Up to 5 weeks after last dose of study treatment
Chemotherapy delays
Will be defined as the proportion of patients requiring delays in chemotherapy during CRT. Differences between treatment arms for categorical or binary end points will be compared using the chi-square test or Fisher's exact test as appropriate. Differences between treatment arms for continuous variables will be compared using the Mann-Whitney U test. Differences between treatment arms for time-to-event end points will be compared using Kaplan-Meier estimates and the log-rank test.
Measured: Up to 5 weeks after last dose of study treatment
Additional olanzapine prescriptions
Will be defined as the proportion of patients prescribed olanzapine for intractable nausea during CRT.
Measured: Up to 5 weeks after last dose of study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2025
- Study start24 Dec 2025
- Primary completion15 Nov 2030 (estimated)
- Study completion15 Nov 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cancer-Associated AnorexiaStudies of the same condition, open and under way.
- More trials run by Roswell Park Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 66 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Roswell Park Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Anurag K Singh, Principal investigator, Roswell Park Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06995508
- Sponsor's protocol ID
- I 3757323
- Other IDs
- NCI-2025-03335, I 3757323
- Status last verified
- Aug 2026
- First submitted
- 12 May 2025
- Last updated
- 18 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Managing Anorexia During Chemoradiation With Olanzapine (MACRO)
- ClinicalTrials.gov ID
- NCT06995508
- Acronym / sponsor ID
- I 3757323
- Conditions
- Cancer-Associated Anorexia, Head and Neck Squamous Cell Carcinoma, Neck Squamous Cell Carcinoma of Unknown Primary
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 66 participants (estimated)
- Lead sponsor
- Roswell Park Cancer InstituteUniversity, hospital or other
- Study start
- 24 Dec 2025 (actual)
- Primary completion
- 15 Nov 2030 (estimated)
- Study completion
- 15 Nov 2031 (estimated)
- First posted
- 29 May 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVE:
- To assess the effect of adding olanzapine to standard symptom management on preventing weight loss during chemoradiation.
SECONDARY OBJECTIVES:
- To assess the effect of olanzapine on:
- Preventing severe weight loss;
- The rate of toxicities-unrelated, possibly- or probably- related to the symptom management regimen (regardless of causality)
II, Quality of Life (QOL) scores:
- With particular attention to nausea, vomiting, appetite, loss, swallowing, pain; and Special attention to sleep;
- Opiate use, hospitalization rate, feeding tube use, chemotherapy delays, and additional olanzapine prescriptions.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive standard of care symptom management on study per the discretion of the treating institution.
ARM II: 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.
After completion of study treatment, patients are followed up at 5 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (standard of care) | Active comparator | Other: Best Practice, Other: Questionnaire AdministrationPatients receive standard of care symptom management on study per the discretion of the treating institution. |
| Arm II (olanzapine, standard of care) | Experimental | Other: Best Practice, Drug: Olanzapine, Other: Questionnaire AdministrationStarting 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (11 listed)
- Eligible for palliative-intent radiation therapy only
- Patients with a feeding tube
- Regular systemic steroid use
- Atypical antipsychotic use
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Best PracticeAlso: standard of care, standard therapyGiven standard of care symptom management | Other | Arm I (standard of care), Arm II (olanzapine, standard of care) |
| OlanzapineAlso: LY 170053, Zyprexa, Zyprexa ZydisGiven PO | Drug | Arm II (olanzapine, standard of care) |
| Questionnaire AdministrationAncillary studies | Other | Arm I (standard of care), Arm II (olanzapine, standard of care) |
Primary outcome
Average change in weight
Time frame: From baseline to patient lowest weight during chemoradiation therapy (CRT) treatment, assessed up to 5 weeks after last dose of study treatment
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.
10 secondary outcomes
Proportion of patients with severe weight loss
Time frame: 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
Time frame: Up to 5 weeks after last dose of study treatment
Change in quality of life (QOL) scores
Time frame: Baseline up to 5 weeks after last dose of study treatment
Change in Quality of Life
Time frame: Up to 5 weeks after last dose of study treatment
Changes in sleep
Time frame: Baseline up to 5 weeks after last dose of study treatment
Opiate use
Time frame: Up to 5 weeks after last dose of study treatment
Hospitalization rate
Time frame: Up to 5 weeks after last dose of study treatment
Feeding tube use
Time frame: Up to 5 weeks after last dose of study treatment
Chemotherapy delays
Time frame: Up to 5 weeks after last dose of study treatment
Additional olanzapine prescriptions
Time frame: Up to 5 weeks after last dose of study treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Anurag K Singh principal investigator
Roswell Park Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Best Practice, Olanzapine and Questionnaire Administration in people with Cancer-Associated Anorexia and Head and Neck Squamous Cell Carcinoma, run by Roswell Park Cancer Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 18 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Average change in weight (time frame: From baseline to patient lowest weight during chemoradiation therapy (CRT) treatment, assessed up to 5 weeks after last dose of study treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Aug 2026.