ACTO: A Phase II, Randomized, Placebo-Controlled Study Evaluating Olanzapine in the Management of Cancer Cachexia
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 66
- 试验地点
- 1
- 主要终点
- Proportion of patients exhibiting weight gain greater 5%
研究概览
简要总结
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).
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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≥
- •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
研究组 & 干预措施
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.
干预措施: Placebo Administration (Drug)
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.
干预措施: Olanzapine (Drug)
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.
干预措施: Olanzapine (Drug)
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.
干预措施: Questionnaire Administration (Other)
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.
干预措施: Questionnaire Administration (Other)
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.
干预措施: Questionnaire Administration (Other)
结局指标
主要结局
Proportion of patients exhibiting weight gain greater 5%
时间窗: Baseline to 12 weeks from baseline
\>5% weight gain comparing olanzapine 2.5mg (Arm I) vs. placebo (Arm III)
次要结局
- Change in Weight(Baseline to 12 weeks from baseline)
- Patient Reported Quality of Life(Baseline to 12 weeks from baseline)
- Patient-reported impression of change(At 12 weeks from baseline)
- Patient Reported Symptoms(At 4, 8, and 12 weeks from baseline)
- Incidence of adverse events(At 4, 8, and 12 weeks from baseline)
- Proportion of patients with ≥1 unplanned hospitalization(From baseline to 12 weeks)
- Proportion of patients with ≥1 emergency department visit(At baseline and at 4, 8, and 12 weeks from baseline)
- Appetite(Baseline up to 12 weeks from baseline)
- Nutrition(At baseline and at 4, 8, 12 weeks from baseline)
- Anorexia(At 12 weeks from baseline])
- Physical Function(At baseline and at 4, 8, and12 weeks from baseline)
- Proportion of patients with ≥1 unplanned hospitalization(At baseline and at 4, 8, and 12 weeks from baseline)
研究者
Eric Roeland, M.D.,FASCO, FAAHPM
Principal Investigator
OHSU Knight Cancer Institute