Olanzapine for the Management of Cancer Associated Appetite Loss in Patients With Advanced Esophagogastric, Hepatopancreaticobiliary, Colorectal or Lung Cancer

NCT ID: NCT05705492

Last Updated: 2026-01-21

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 66 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-07-17
• Study Completion Date: 2026-12-31

Brief Summary

This phase II trial tests how well olanzapine works in managing cancer cachexia in patients experiencing esophagogastric, hepatopancreaticobiliary, colorectal, or lung cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic) -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 drug that targets key neurotransmitters (a type of molecule in the central nervous system that transmits messages to the rest of the body) that may stimulate appetite, restore caloric intake, minimize weight loss, and improve quality of life (QOL).

Detailed Description

PRIMARY OBJECTIVE:

I. To assess the impact of olanzapine 2.5 mg versus (vs) placebo on the proportion of patients with locally advanced or metastatic EG, HPB, or lung cancers receiving first-line systemic standard-of-care (SOC) therapy with >5% weight gain over 12 weeks. (Part A)

SECONDARY OBJECTIVE:

I. To evaluate the impact of olanzapine 2.5 mg and placebo vs olanzapine 5 mg on the proportion of patients with >5% weight gain over 12 weeks. (Part A) II. To evaluate the impact of olanzapine 2.5 mg vs olanzapine 5 mg vs placebo on additional cancer cachexia-associated endpoints over 12 weeks (anorexia, nutritional status, physical function, patient-reported symptoms, QOL, safety and toxicity, and healthcare utilization) over 12 weeks. (Part A)

OUTLINE:

PART A: Patients are randomized to 1 of 3 arms. All three arms have an optional baseline computed tomography (CT) scan (timed with standard-of-care imaging) at baseline and optional monthly blood sample collections.

ARM I: Patients receive a lower (2.5 mg) dose of olanzapine orally (PO) nightly for 12 weeks in the absence of unacceptable toxicity. Patients may choose to enroll in an additional 12 weeks of treatment (Part B). Patients may choose to participate to undergo CT scan and collection of blood samples on study.

ARM II: Patients receive a higher (5 mg) dose of olanzapine PO nightly for 12 weeks in the absence of unacceptable toxicity. Patients may choose to enroll in an additional 12 weeks of treatment. Patients may choose to participate to undergo CT scan and collection of blood samples on study.

ARM III: Patients receive placebo PO nightly for 12 weeks in the absence of unacceptable toxicity. Patients may choose to enroll in an additional 12 weeks of treatment. Patients may choose to participate to undergo CT scan and collection of blood samples on study.

PART B: All patients receive a lower (2.5mg) dose of olanzapine PO nightly for 12 additional weeks in the absence of unacceptable toxicity. Patients may choose to participate in additional blood sample collections.

After completion of study treatment, patients are followed up at 1 week.

Conditions

Advanced Malignant Solid Neoplasm; Advanced Biliary Tract Carcinoma; Advanced Esophageal Carcinoma; Metastatic Esophageal Carcinoma; Locally Advanced Colorectal Carcinoma; Locally Advanced Esophageal Carcinoma; Locally Advanced Gastric Carcinoma; Metastatic Colorectal Carcinoma (mCRC); Advanced Lung Carcinoma; Locally Advanced Hepatocellular Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: DOUBLE

Study Groups

Arm I (olanzapine, optional biospecimen collection)

Patients receive a lower (2.5mg) dose of olanzapine orally (PO) nightly for 12 weeks in the absence of unacceptable toxicity. Patients may choose to enroll in an additional 12 weeks of treatment. Patients can choose to undergo computed tomography (CT) scan at baseline and monthly blood sample collections on study.

Group Type: EXPERIMENTAL

Olanzapine

Intervention Type: DRUG

Given PO

Questionnaire Administration

Intervention Type: OTHER

Ancillary studies

Arm II

Patients receive a higher dose (5 mg) of olanzapine PO nightly for 12 weeks in the absence of unacceptable toxicity. Patients may choose to enroll in an additional 12 weeks of treatment. Patients undergo an optional baseline CT scan and collections of monthly blood samples on study.

Group Type: EXPERIMENTAL

Olanzapine

Intervention Type: DRUG

Given PO

Questionnaire Administration

Intervention Type: OTHER

Ancillary studies

Arm III

ARM III: Patients receive placebo PO nightly for 12 weeks in the absence of unacceptable toxicity. Patients may choose to enroll in an additional 12 weeks of treatment. Patients undergo CT scan and monthly collection of blood samples on study.

Group Type: PLACEBO_COMPARATOR

Placebo Administration

Intervention Type: DRUG

Given PO

Questionnaire Administration

Intervention Type: OTHER

Ancillary studies

Interventions

Olanzapine

Given PO

Intervention Type: DRUG

Placebo Administration

Given PO

Intervention Type: DRUG

Questionnaire Administration

Ancillary studies

Intervention Type: OTHER

Other Intervention Names

LY 170053; Zyprexa; Zyprexa Zydis

Eligibility Criteria

Inclusion Criteria

• Willingness to provide written informed consent
• Individuals >= 18 years of age
• Histologically confirmed advanced local or metastatic esophogastric, hepatopancreaticobiliary, colorectal, or lung cancer diagnosis within 12 weeks of screening
• Patients with weight loss as defined by international consensus criteria (documented or patient-reported):

• ≥ 5% weight loss over the past 6 months
• ≥ 2% weight loss with body mass index (BMI) <20 kg/m^2 or sarcopenia
• Planned or ongoing first-line palliative antineoplastic therapy (cytotoxic chemotherapy, targeted therapy, immunotherapy, combinations) with or without radiation therapy and have not started the second cycle of first-line palliative antineoplastic therapy. Patients may have received adjuvant antineoplastic therapy at least 6 months prior to screening
• Able to ambulate independently with or without assistive devices (e.g., cane, walker)
• In the case of brain metastases, the individual must be asymptomatic or previously treated with a full cycle of therapy with recovery from any acute effects of radiation therapy or surgery before 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
• 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 principal investigators [PI's] discretion) and thereafter while on the study
• Willingness to comply with restrictions on chest/breastfeeding
• 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 (BL) must be obtained for individuals capable of childbearing

Exclusion Criteria

• Plan for, or history of (within 30 days of enrollment), 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
• Current use of medications or supplements with the goal of enhancing appetite within ≥14 days, including:

• megestrol acetate
• cannabinoids (including, but not limited to dronabinol, medical cannabis, over the counter [OTC] cannabinoid products), and/or
• Corticosteroids (defined as ≥ 5mg of prednisone [or equivalent per day]), except for standard-of-care chemotherapy-induced nausea and vomiting prophylaxis
• Known history of poorly controlled diabetes, defined as fasting morning blood sugars ≥300 mg/dL or recent hemoglobin A1≥ 8. Individuals with diabetes will undergo hemoglobin A1c (HbA1c) blood testing if they do not have HbA1c results 12 weeks prior to enrollment
• Inadequate organ function, which may include, but is not limited to, the following laboratory results within 28 days before signing consent:

• Total bilirubin ≥5x upper limit of normal (ULN), aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SPGT]) ≥5X ULN (unless the participant has documented Gilbert's syndrome, hepatocellular carcinoma, or hepatic metastases)
• Primary investigator (PI) discretion will determine continued eligibility after randomization occurs in the event the liver function test results are above the proposed ULN
• Renal disease requiring dialysis 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
• Tube feeding or parenteral nutrition at the time of screening
• 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 at randomization make the individual unsuitable for the study in the judgment of the 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
• 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 PI's judgment, makes the participant inappropriate for the study

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Oregon Health and Science University

OTHER

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

OHSU Knight Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Eric Roeland, M.D.,FASCO, FAAHPM

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Eric Roeland, M.D., FAAHPM, FASCO

Role: PRINCIPAL_INVESTIGATOR

OHSU Knight Cancer Institute

Locations

OHSU Knight Cancer Institute

Portland, Oregon, United States

Site Status: RECRUITING

Countries

United States

Facility Contacts

Eric Roeland, M.D., FAAHPM, FASCO

Role: primary

roeland@ohsu.edu

503-494-8534

Other Identifiers

P30CA069533

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2022-10209

Identifier Type: REGISTRY

Identifier Source: secondary_id

STUDY00024724

Identifier Type: OTHER

Identifier Source: secondary_id

STUDY00024724

Identifier Type: -

Identifier Source: org_study_id