Olanzapine for the Management of Cancer Associated Appetite Loss in Patients With Advanced and Incurable Solid Tumors
Study Details
Study Description
Brief Summary
This phase II trial tests how well olanzapine may work in managing cancer cachexia in patients experiencing advanced solid tumor cancer-associated appetite loss while receiving non-curative cancer therapy. Loss of appetite ("anorexia") in the setting of cancer is a key feature of "cachexia," a syndrome associated with loss of weight and muscle as well as weakness and fatigue. Olanzapine is a type of drug that targets key neurotransmitters (a type of molecule used by the brain to transmit messages to the rest of the body) that may stimulate appetite, restore caloric intake, minimize weight loss, and improve quality of life.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
PRIMARY OBJECTIVE:
- To assess the effect of olanzapine versus placebo for decreasing cancer-associated anorexia at 2 weeks for patients with advanced cancer receiving systemic therapy.
SECONDARY OBJECTIVE:
- To evaluate the longitudinal impact of olanzapine versus placebo over 6 weeks on food intake, anthropometric measures, physical function, patient-reported symptoms, quality of life, toxicity, and healthcare utilization.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive 5mg of olanzapine orally (PO) nightly for six weeks on study. Patients may also undergo an optional computed tomography (CT) scan and blood sample collection on the study.
ARM II: Patients receive placebo PO nightly for six weeks and then receive 5mg of olanzapine PO nightly for 6 weeks (i.e., wait-list control). Patients may also undergo an optional CT scan and collection of blood samples on the study.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Arm I (olanzapine, optional biospecimen collection) Patients receive olanzapine PO for six weeks on study. Patients may also undergo an optional CT scan and blood sample collection on the study. |
Procedure: Biospecimen Collection
Undergo blood specimen collection
Other Names:
Procedure: Computed Tomography
Undergo a CT scan
Other Names:
Drug: Olanzapine
Given PO
Other Names:
Other: Questionnaire Administration
Ancillary studies
|
| Placebo Comparator: Arm II (placebo, olanzapine, optional biospecimen collection) Patients receive placebo PO for six weeks and then receive olanzapine PO for 6 weeks. Patients also undergo an optional CT scan and collection of blood samples on study. |
Procedure: Biospecimen Collection
Undergo blood specimen collection
Other Names:
Procedure: Computed Tomography
Undergo a CT scan
Other Names:
Drug: Olanzapine
Given PO
Other Names:
Drug: Placebo Administration
Given PO
Other: Questionnaire Administration
Ancillary studies
|
Outcome Measures
Primary Outcome Measures
- Change in self-reported severity of anorexia [Baseline to 2 weeks]
Measured using the 5-item Functional Assessment of Anorexia-Cachexia Therapy (FAACT) assessment. Numerical scale goes from 0-20, with higher scores indicate less anorexia/cachexia.
Secondary Outcome Measures
- Food intake [At to 2, 4, and 6 weeks from baseline]
Measured using Ingesta score. The Ingesta food intake scoring tool is and 11-point numerical scale over 24 hours going 0 (eating nothing at all) to 10 (eating as usual).
- Anthropometric measures: weight (kg) [At 2, 4, and 6 weeks from baseline]
Weight will be captured using the same properly calibrated scale at the same time of day without shoes.
- Anthropometric measures: body mass index (kg/m^2) [At 2, 4, and 6 weeks from baseline]
Weight will be captured using the same properly calibrated scale at the same time of day without shoes.
- Physical function: performance status [At 2, 4, and 6 weeks from baseline]
Measured using Eastern Cooperative Oncology Group (ECOG) performance status. ECOG is a clinician's assessment of physical function rated on numerical scale going from 0 (fully active) to 5 (dead).
- Physical function: short physical battery assessment [At 2, 4, and 6 weeks from baseline]
Measured using a Short Physical Performance Battery assessment (SPPB), a physical function assessment consisting of 3 timed measures and scored 0 to 12. Scores of 2 or lower indicate mobility disability and 10 or higher indicate no mobility disability / robustness.
- Physical function: handgrip strength [At 2, 4, and 6 weeks from baseline]
Handgrip strength (HGS) will be measured in kilograms (kg) by handgrip dynamometry to assess arm strength.
- Patient-reported symptoms and quality of life: FACT-G [At 2, 4, and 6 weeks from baseline]
Measured using Functional Assessment of Cancer Therapy - General (FACT-G) Scores go from 0-108, higher scores indicate better QOL, including physical (0-28), social (0-28), emotional (0-24), and functional (0-28).
- Patient-reported symptoms and quality of life: FAACT [At 2, 4, and 6 weeks from baseline]
Measured using the longitudinal changes on the Functional Assessment of Anorexia-Cachexia Therapy (FAACT). Scale goes from 0-20, with higher scores indicate less anorexia/cachexia
- Patient-reported symptoms and quality of life: PRO-CTCAE [At 2, 4, and 6 weeks from baseline]
Measured using Patient Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Scores go from 0-4 for each item, higher scores indicate more severity, specifically none (0), mild (1), moderate (2), severe (3), and very severe (4).
- Patient-reported symptoms and quality of life: PGI-C [At 2, 4, and 6 weeks from baseline]
Measured using Patient Global Impression of Change (PGI-C) assessments. This measure patient belief about the overall treatment efficacy. Scores go from 0-14, higher scores indicate greater global improvement.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Willingness to provide written informed consent. For decisional impairment or conditions that render the individual unable to independently provide consent, a legally authorized representative must be available or designated in conjunction with the study consent process
-
Individuals >= 18 years of age of all races, ethnicities, sexual orientations, gender identities, and abilities may be screened for enrollment without bias
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Histologically confirmed advanced and incurable solid tumor cancer diagnosis within 12 weeks of screening. Cancer diagnoses will include those for which standard curative measures do not exist or are no longer effective
-
Planned or ongoing standard of care (SOC) systemic antineoplastic therapy without curative intent (concurrent to this study)
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Able to ambulate independently with or without assistive devices (e.g., cane, walker).
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In the case of brain metastases, the individual must be asymptomatic or previously treated with a full cycle of therapy such that recovery from any acute effects of radiation therapy or surgery has occurred before the screening. Such individuals must have discontinued corticosteroid treatment and be neurologically stable for at least 4 weeks before screening
-
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
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Able and willing to discontinue the use of any drug or over-the-counter (OTC) product that may interact with the study drug (within a period sufficient for wash-out per the investigator's discretion) and thereafter while on the study
-
Willingness to comply with restrictions on chest/breastfeeding
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Individuals capable of childbearing and contributing viable sperm must be willing to comply with contraception requirements and not donate ova or sperm while on the study and for 1 month after that
-
A negative pregnancy test at baseline must be obtained for individuals capable of childbearing
Exclusion Criteria:
-
Plan for, or history of (within 30 days of registration), the use of an antipsychotic drug, including, but not limited to risperidone, quetiapine, clozapine, phenothiazine, or butyrophenone. This limitation does not include prochlorperazine and other phenothiazines as antiemetic therapy. The use of antipsychotics concurrent with protocol therapy will not be allowed
-
Previous or current use of megestrol acetate, cannabinoids (including, but not limited to dronabinol, medical cannabis, over the counter [OTC] cannabinoids products), and/or corticosteroids (defined as >= 5mg of prednisone or equivalent per day, except for standard chemotherapy-induced nausea and vomiting [CINV] prophylaxis) during the proceeding >=14 days
-
Known history of poorly controlled diabetes, defined as fasting morning blood sugars > 300 mg/dL or recent hemoglobin A1c >= 8
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Inadequate organ function, which may include, but is not limited to, the following laboratory results within 28 days before signing consent:
-
Total bilirubin > upper limit of normal (ULN), aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SPGT]) > 2.5 ULN (unless the participant has documented Gilbert's syndrome, hepatocellular carcinoma, or hepatic metastases)
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Serum creatinine > 2.0 mg/dL or calculated glomerular filtration rate (GFR) >= 30 mL/minute/1.73 m^2 as calculated by the modification of diet in renal disease (MDRD) equation
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NOTE: Investigator discretion will determine continued eligibility after randomization occurs in the event the liver function test results are greater than (>) the proposed upper limit of normal
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Tube feeding or parenteral nutrition at the time of screening
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Any condition that may negatively impact oral absorption of the study drug (including, but not limited to dysphagia, mucositis, gastrectomy, colitis, bowel obstruction, high output ileostomy) or any plan to undergo an intervention that will render such a condition
-
Recurrent ascites unresponsive to medical interventions and requires therapeutic paracentesis
-
Uncontrolled symptoms (including, but not limited to, pain and nausea) at randomization make the individual unsuitable for the study in the judgment of the principal investigator (PI). If uncontrolled symptoms can be effectively palliated for
= 1 week prior, enrollment may be considered at the discretion of the PI
-
Uncontrolled infection, including coronavirus disease 2019 (COVID-19), at time of randomization. Individuals with the uncontrolled infection will not be eligible as the symptomology of infection may obscure the outcomes of this study
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Other medical or psychiatric condition, including recent (within 1 year) or active suicidal ideation/behavior or laboratory abnormality, may increase the risk of study participation or, in the investigator's judgment, makes the participant inappropriate for the study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | OHSU Knight Cancer Institute | Portland | Oregon | United States | 97239 |
Sponsors and Collaborators
- OHSU Knight Cancer Institute
- Oregon Health and Science University
Investigators
- Principal Investigator: Eric Roeland, M.D., FAAHPM, OHSU Knight Cancer Institute
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- STUDY00024724
- NCI-2022-10209
- STUDY00024724