Trial Title:
Olanzapine for the Management of Cancer Associated Appetite Loss in Patients With Advanced Solid or or Metastatic Esophagogastric, Hepatopancreaticobiliary, or Lung Cancer
NCT ID:
NCT05705492
Condition:
Advanced Malignant Solid Neoplasm
Advanced Biliary Tract Carcinoma
Advanced Esophageal Carcinoma
Metastatic Esophageal Carcinoma
Conditions: Official terms:
Carcinoma
Esophageal Neoplasms
Olanzapine
Conditions: Keywords:
cancer
cachexia
weight loss
loss of appetite
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Supportive Care
Masking:
Double (Participant, Investigator)
Intervention:
Intervention type:
Drug
Intervention name:
Olanzapine
Description:
Given PO
Arm group label:
Arm I (olanzapine, optional biospecimen collection)
Arm group label:
Arm II
Other name:
LY 170053
Other name:
Zyprexa
Other name:
Zyprexa Zydis
Intervention type:
Drug
Intervention name:
Placebo Administration
Description:
Given PO
Arm group label:
Arm III
Intervention type:
Other
Intervention name:
Questionnaire Administration
Description:
Ancillary studies
Arm group label:
Arm I (olanzapine, optional biospecimen collection)
Arm group label:
Arm II
Arm group label:
Arm III
Summary:
This phase II trial tests how well olanzapine works in managing cancer cachexia in
patients experiencing esophagogastric (EG), hepatopancreaticobiliary (HPB) 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 type of drug that targets key
neurotransmitters (a type of molecule that is used by the central nervous system to
transmit messages to the rest of the body) that may stimulate appetite, restore caloric
intake, minimize weight loss, and improve quality of life.
Detailed description:
PRIMARY OBJECTIVE:
I. To assess the impact of olanzapine 2.5 mg verses (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 and quality of life (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). Patients may choose to participate 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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Willingness to provide written informed consent.
- Individuals ≥ 18 years of age
- Histologically confirmed locally advanced or metastatic EG, HPB, 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 SOC, first-line systemic antineoplastic therapy (cytotoxic
chemotherapy, targeted therapy, immunotherapy, combinations) with or without
radiation therapy and have not started the second cycle of antineoplastic therapy
- 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 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 (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 SOC chemotherapy-induced nausea and vomiting (CINV) 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 > 5 upper limit of normal (ULN), aspartate aminotransferase
(AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine
aminotransferase (ALT) (serum glutamic pyruvic transaminase [SPGT]) > 5 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 >
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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
OHSU Knight Cancer Institute
Address:
City:
Portland
Zip:
97239
Country:
United States
Status:
Recruiting
Contact:
Last name:
Eric Roeland, M.D., FAAHPM, FASCO
Phone:
503-494-8534
Email:
roeland@ohsu.edu
Investigator:
Last name:
Eric Roeland, M.D., FAAHPM, FASCO
Email:
Principal Investigator
Start date:
July 17, 2024
Completion date:
December 31, 2025
Lead sponsor:
Agency:
OHSU Knight Cancer Institute
Agency class:
Other
Collaborator:
Agency:
Oregon Health and Science University
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
OHSU Knight Cancer Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05705492
