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

NCT05705492 | Recruiting Phase 2 FDA Drug

• 3 other identifiers: STUDY00024724P30CA069533NCI-2022-10209
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

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).

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

Keywords

cancer; cachexia; weight loss; loss of appetite

Outcome Measures

Primary Outcomes (1)

• Proportion of patients exhibiting weight gain greater 5%

  \>5% weight gain comparing olanzapine 2.5mg (Arm I) vs. placebo (Arm III)

  Baseline to 12 weeks from baseline

Secondary Outcomes (14)

• Change in Weight

  Baseline to 12 weeks from baseline

• Anorexia

  At 12 weeks from baseline]

• Appetite

  Baseline up to 12 weeks from baseline

• Nutrition

  At baseline and at 4, 8, 12 weeks from baseline

• Physical Function

  At baseline and at 4, 8, and12 weeks from baseline

Study Arms (3)

Arm I (olanzapine, optional biospecimen collection)

EXPERIMENTAL

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.

Drug: Olanzapine; Other: Questionnaire Administration

Arm II

EXPERIMENTAL

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.

Drug: Olanzapine; Other: Questionnaire Administration

Arm III

PLACEBO COMPARATOR

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.

Drug: Placebo Administration; Other: Questionnaire Administration

Interventions

Questionnaire Administration OTHER

Ancillary studies

Arm I (olanzapine, optional biospecimen collection); Arm II; Arm III

Olanzapine DRUG

Given PO

Also known as: LY 170053, Zyprexa, Zyprexa Zydis

Arm I (olanzapine, optional biospecimen collection); Arm II

Placebo Administration DRUG

Given PO

Arm III

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• National Cancer Institute (NCI): collaborator
• Oregon Health and Science University: collaborator

Study Sites (1)

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

RECRUITING

MeSH Terms

Conditions

Esophageal Neoplasms; Colorectal Neoplasms; Neoplasms; Cachexia; Weight Loss; Anorexia

Interventions

Olanzapine

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Thinness; Signs and Symptoms, Digestive

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Eric Roeland, M.D., FAAHPM, FASCO

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 6, 2023
• First Posted: January 30, 2023
• Study Start: July 17, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 21, 2026

Record last verified: 2026-01

Locations

US (1)