Olanzapine for the Management of Cancer Associated Appetite Loss in Patients With Advanced and Incurable Solid Tumors

Advanced Malignant Solid Neoplasm Clinical Trial

Official title:

ACTO: A Phase II, Randomized, Placebo-Controlled Study Evaluating Olanzapine in the Management of Cancer Cachexia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05705492
• Other study ID #: STUDY00024724
• Secondary ID: NCI-2022-10209ST
• Status: Recruiting
• Phase: Phase 2
• Start date: May 1, 2024
• Est. completion date: December 31, 2025

Study information

• Verified date: April 2024
• Source: OHSU Knight Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II trial tests how well olanzapine may work in managing cancer cachexia in patients living with gastric, hepatopancreaticobiliary 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) 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 (QOL).

Description:

PRIMARY OBJECTIVE:

I. To assess the impact of olanzapine 2.5 mg verses placebo on the proportion of patients with locally advanced or metastatic cancers receiving first-line systemic therapy with > 5% weight gain over 12 weeks. (Part A)

SECONDARY OBJECTIVE:

I. To evaluate the impact of olanzapine 2.5 mg and placebo versus (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 and 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 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).

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 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 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 66
• Est. completion date: December 31, 2025
• Est. primary completion date: June 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Willingness to provide written informed consent.

• Individuals >= 18 years of age of all races, ethnicities, sexual orientations, gender identities, and abilities may be screened for enrollment without bias

• Histologically confirmed locally advanced or metastatic gastric, hepatopancreaticobiliary (HPB), and lung cancers 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), first-line systemic antineoplastic therapy without curative intent (concurrent to this study)

• Able to ambulate independently with or without assistive devices (e.g., cane, walker).

• 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 investigator'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 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

• 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 (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

Related Conditions & MeSH terms

• Advanced Malignant Solid Neoplasm
• Cachexia

Intervention

Procedure:
• Biospecimen Collection
Undergo blood specimen collection
• Computed Tomography
Undergo a CT scan

Drug:
• Olanzapine
Given PO
• Placebo Administration
Given PO

Other:
• Questionnaire Administration
Ancillary studies

Locations

Country	Name	City	State
United States	OHSU Knight Cancer Institute	Portland	Oregon

Sponsors (3)

Lead Sponsor	Collaborator
OHSU Knight Cancer Institute	National Cancer Institute (NCI), Oregon Health and Science University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in weight	>5% weight gain comparing olanzapine 2.5mg (Arm 1) vs. placebo (Arm 3)	Baseline to 12 weeks from baseline
Secondary	>5% weight gain comparing olanzapine 2.5mg vs. olanzapine 5mg vs. placebo	Weight	At baseline, 12 weeks from baseline
Secondary	Patient-reported anorexia comparing olanzapine 2.5mg vs. olanzapine 5mg vs. placebo	Functional Assessment of Anorexia-Cachexia Therapy (FAACT) =37 Visual analog scale	At baseline and 4, 8, 12 and 12 weeks from baseline
Secondary	Nutrition	Patient-Generated Subjective Global Assessment Short Form (PG-SGA-SF)	At baseline and 12 weeks from baseline
Secondary	Physical function: performance status	Eastern Cooperative Oncology Group (ECOG) performance status	At baseline, 4, 8, and 12 weeks from baseline
Secondary	Patient-reported quality of life	Functional Assessment of Cancer Therapy - General (FACT-G)	At baseline and at 4, 8, and12 weeks from baseline
Secondary	Patient-reported symptoms and quality of life	Patient Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)	At 2, 4, and 6 weeks from baseline
Secondary	Incidence of adverse events	National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.	At baseline, 4, 8, and 12 weeks from baseline
Secondary	Health Care Utilization	Emergency department visits and unplanned hospitalizations	At 4, 8, and 12 weeks from baseline
Secondary	CT scan (optional)	Body composition analysis	At baseline, if available per standard of care
Secondary	Serum Biomarkers (optional)	C-reactive protein (CRP), interleukin-6 (IL-6), lpocalin-2 (LCN2), growth differentiation factor 15 (GDF-15)	At baseline and at 4, 8, and 12 weeks from baseline