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

• ClinicalTrials.gov Identifier: NCT05705492
• Recruitment Status: Recruiting
• First Posted: January 30, 2023
• Last Update Posted: May 2, 2024
• Sponsor: OHSU Knight Cancer Institute
• Collaborators: Oregon Health and Science University; National Cancer Institute (NCI)
• Information provided by (Responsible Party): Eric Roeland, M.D., FAAHPM, FASCO, OHSU Knight Cancer Institute

Tracking Information

• First Submitted Date: January 6, 2023
• First Posted Date: January 30, 2023
• Last Update Posted Date: May 2, 2024
• Estimated Study Start Date: May 1, 2024
• Estimated Primary Completion Date: June 1, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 30, 2024)

Change in weight [ Time Frame: Baseline to 12 weeks from baseline ]

>5% weight gain comparing olanzapine 2.5mg (Arm 1) vs. placebo (Arm 3)

Original Primary Outcome Measures (submitted: January 27, 2023)

Change in self-reported severity of anorexia [ Time Frame: 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.

Current Secondary Outcome Measures (submitted: April 30, 2024)

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

Original Secondary Outcome Measures (submitted: January 27, 2023)

• Food intake [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Olanzapine for the Management of Cancer Associated Appetite Loss in Patients With Advanced and Incurable Solid Tumors
• Official Title: ACTO: A Phase II, Randomized, Placebo-Controlled Study Evaluating Olanzapine in the Management of Cancer Cachexia
• Brief 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).

Detailed 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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Supportive Care
• Condition: Advanced Malignant Solid Neoplasm

Intervention

• Procedure: Biospecimen Collection
  Undergo blood specimen collection
  Other Names:

  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
• Procedure: Computed Tomography
  Undergo a CT scan
  Other Names:

  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT
  • CT Scan
  • tomography
• Drug: Olanzapine
  Given PO
  Other Names:

  • LY 170053
  • Zyprexa
  • Zyprexa Zydis
• Drug: Placebo Administration
  Given PO
• Other: Questionnaire Administration
  Ancillary studies

Study Arms

• Experimental: 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.
  Interventions:

  • Procedure: Biospecimen Collection
  • Procedure: Computed Tomography
  • Drug: Olanzapine
  • Other: Questionnaire Administration
• Experimental: 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.
  Interventions:

  • Procedure: Biospecimen Collection
  • Procedure: Computed Tomography
  • Drug: Olanzapine
  • Other: Questionnaire Administration
• Placebo Comparator: 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.
  Interventions:

  • Procedure: Biospecimen Collection
  • Procedure: Computed Tomography
  • Drug: Placebo Administration
  • Other: Questionnaire Administration

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 30, 2024): 66
• Original Estimated Enrollment (submitted: January 27, 2023): 44
• Estimated Study Completion Date: December 31, 2025
• Estimated Primary Completion Date: June 1, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05705492
• Other Study ID Numbers: STUDY00024724; NCI-2022-10209 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); STUDY00024724 ( Other Identifier: OHSU Knight Cancer Institute ); P30CA069533 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Eric Roeland, M.D., FAAHPM, FASCO, OHSU Knight Cancer Institute
• Original Responsible Party: Eric Roeland, M.D., FAAHPM, OHSU Knight Cancer Institute, Principal Investigator
• Current Study Sponsor: OHSU Knight Cancer Institute
• Original Study Sponsor: Same as current

Collaborators

• Oregon Health and Science University
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Eric Roeland, M.D., FAAHPM, FASCO; OHSU Knight Cancer Institute

• PRS Account: OHSU Knight Cancer Institute
• Verification Date: April 2024