Olanzapine Versus Megestrol Acetate for the Treatment of Loss of Appetite Among Advanced Cancer Patients

Sponsor

Alliance for Clinical Trials in Oncology (Other)

Overall Status

Recruiting

CT.gov ID

NCT04939090

Collaborator

National Cancer Institute (NCI) (NIH)

360

Enrollment

Locations

Arms

25.5

Anticipated Duration (Months)

5.3

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This phase III trial compares the effects of olanzapine versus megestrol acetate in treating loss of appetite in patients with cancer that has spread to other places in the body (advanced). Olanzapine may stimulate and increase appetite. This study aims to find out if olanzapine is better than the usual approach (megestrol acetate) for stimulating appetite and preventing weight loss.

Condition or Disease	Intervention/Treatment	Phase
Advanced Malignant Solid Neoplasm Anorexia Hematopoietic and Lymphoid Cell Neoplasm	Drug: Olanzapine Drug: Megestrol Acetate Other: Questionnaire Administration	Phase 3

Detailed Description

The primary and secondary objectives of the study:

PRIMARY OBJECTIVE:

To determine whether olanzapine leads to greater appetite improvement from baseline in cancer patients suffering from anorexia compared to megestrol acetate using the 0-10 numerical rating scale (NRS).

SECONDARY OBJECTIVES:

To determine whether olanzapine leads to a greater proportion of patients who report a 5% or greater weight gain from baseline compared to megestrol acetate.
To compare change in cachexia/anorexia symptoms with olanzapine compared to megestrol acetate using the Functional Assessment of Anorexia/Cachexia Treatment (FAACT)-Anorexia/Cachexia Subscale (A/CS) instrument.

OUTLINE: Patient are randomized to 1 of 2 arms.

ARM I: Patients receive olanzapine orally (PO) once daily (QD) for up to 4 weeks in the absence of consent withdrawal or unacceptable toxicity.

ARM II: Patients receive megestrol acetate PO QD for up to 4 weeks in the absence of consent withdrawal or unacceptable toxicity.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

360 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Supportive Care

Official Title:

A Randomized Phase III Trial of Olanzapine Versus Megestrol Acetate for Cancer-Associated Anorexia

Actual Study Start Date :

Oct 15, 2021

Anticipated Primary Completion Date :

Apr 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (olanzapine) Patients receive olanzapine PO QD for up to 4 weeks in the absence of disease progression or unacceptable toxicity.	Drug: Olanzapine Given PO Other: Questionnaire Administration Ancillary studies
Active Comparator: Arm II (megestrol acetate) Patients receive megestrol acetate PO QD for up to 4 weeks in the absence of disease progression or unacceptable toxicity.	Drug: Megestrol Acetate Given PO Other: Questionnaire Administration Ancillary studies

Arm

Intervention/Treatment

Experimental: Arm I (olanzapine)

Patients receive olanzapine PO QD for up to 4 weeks in the absence of disease progression or unacceptable toxicity.

Drug: Olanzapine

Given PO

Other: Questionnaire Administration

Ancillary studies

Active Comparator: Arm II (megestrol acetate)

Patients receive megestrol acetate PO QD for up to 4 weeks in the absence of disease progression or unacceptable toxicity.

Drug: Megestrol Acetate

Given PO

Other: Questionnaire Administration

Ancillary studies

Outcome Measures

Primary Outcome Measures

Change in appetite [Baseline up to 4 weeks]
Will be compared between the two study groups (olanzapine versus megestrol acetate) using a 0-10 numerical rating scale. Will be summarized by mean (standard deviation [SD]) and median (range) by treatment arm. The difference in appetite change from baseline to 4 weeks of treatment between arms will be estimated along with a 95% confidence interval and will be compared using a t-test or Wilcoxon rank-sum test as appropriate.

Secondary Outcome Measures

Proportion of patients who report a 5% or greater weight gain [Baseline up to 4 weeks]
The proportion of patients with a 5% or greater weight gain from baseline will be calculated for each arm. The difference in proportion of patients with 5% or greater weight gain between the arms will be estimated along with a 95% confidence interval using a normal approximation of the binomial distribution and will be compared using a Chi-squared test.
Change in well-being status and cachexia/anorexia symptoms [Baseline up to 4 weeks]
Responses to the Functional Assessment of Anorexia/Cachexia Treatment (FAACT)-Anorexia/Cachexia Subscale (A/CS) questionnaire will be scored according to the established algorithm. The total score of the FAACT-A/CS will be summarized weekly and the change from baseline to 4 weeks will be compared between the treatment arms using the same methods described for the primary endpoint.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Women and men of reproductive potential should agree to use an appropriate method of birth control throughout their participation in this study due to the teratogenic potential of the therapy utilized in this trial. Appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives or double barrier method (diaphragm plus condom)
Diagnosis of advanced cancer
Patient-reported 2-month weight loss of at least 5 pounds (2.3 kilograms) and/or physician-estimated caloric intake of less than 20 calories/kilogram of body weight per day
The patient must perceive loss of appetite and/or weight as a problem; and have an appetite score of 4 or worse on the "Please rate your appetite…." question that requires a patient response on a 0-10 numeric rating scale
Not receiving ongoing tube feedings or parenteral nutrition at the time of registration
Not currently using systemic adrenal steroids (with the exception of short-term dexamethasone within 3 days of chemotherapy for control of chemotherapy side effects)
No use of androgens, progesterone analogs, or other appetite stimulants within the past month
Patient should not have poorly controlled hypertension or congestive heart failure at registration
Patient should not have an obstruction of the alimentary canal, malabsorption, or intractable vomiting (defined as vomiting more than 3 times per day over the preceding week)
Not currently using olanzapine for another medical condition or had previously used olanzapine for chronic nausea or for any pre-existing psychotic disorder
Patient should not have had a previous blood clot at any time in the past
No history of poorly controlled diabetes
No symptomatic leptomeningeal disease or known brain metastases as these patients may have difficulty taking oral medications
No history of hypersensitivity to olanzapine or megestrol acetate
No COVID-19 infection in the past that, in the opinion of the treating physician, had left patients with compromised taste, which has not resolved at the time of registration
Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown. Therefore, for women of childbearing potential only, a negative urine or serum pregnancy test done =< 14 days prior to registration is required
Age >= 18 years
Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
Estimated life expectancy of 3 months or longer
Serum creatinine =< 2.0 mg/dL
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 3 x upper limit of normal (ULN)
Fasting glucose > 1410 mg/dl
Granulocytes > 1000/hpf
No treatment with another antipsychotic agent, such as risperidone, quetiapine, clozapine, butyrophenone within 30 days of enrollment
In order to complete the mandatory patient-completed measures, participants must be able to speak and/or read English or Spanish. Sites seeking to enroll Spanish-speaking patients should have access to Spanish speaking staff on site or through the use of a translation service to be able to conduct the informed consent discussion in Spanish, and to conduct the weekly phone calls

Exclusion Criteria:

Psychiatric illness which would prevent the patient from giving informed consent
Medical condition such as uncontrolled infection (including human immunodeficiency virus [HIV]), uncontrolled diabetes mellitus or cardiac disease which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient
Patients who cannot swallow oral formulations of the agents
Patients with impaired decision-making capacity (such as with a diagnosis of dementia or memory loss) are not eligible for this study
No presence of a hormone-sensitive tumor, such as breast, endometrial, or prostate cancer (this exclusion criterion is intended to circumvent any confounding antineoplastic effects of megestrol acetate)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mountain Blue Cancer Care Center - Swedish	Englewood	Colorado	United States	80113
2	Rocky Mountain Cancer Centers-Lakewood	Lakewood	Colorado	United States	80228
3	Rocky Mountain Cancer Centers-Sky Ridge	Lone Tree	Colorado	United States	80124
4	Rocky Mountain Cancer Centers-Thornton	Thornton	Colorado	United States	80260
5	Rush - Copley Medical Center	Aurora	Illinois	United States	60504
6	Illinois CancerCare-Bloomington	Bloomington	Illinois	United States	61704
7	Illinois CancerCare-Canton	Canton	Illinois	United States	61520
8	Illinois CancerCare-Carthage	Carthage	Illinois	United States	62321
9	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois	United States	62526
10	Illinois CancerCare-Dixon	Dixon	Illinois	United States	61021
11	Crossroads Cancer Center	Effingham	Illinois	United States	62401
12	Illinois CancerCare-Eureka	Eureka	Illinois	United States	61530
13	Illinois CancerCare-Galesburg	Galesburg	Illinois	United States	61401
14	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois	United States	61443
15	Illinois CancerCare-Macomb	Macomb	Illinois	United States	61455
16	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois	United States	61350
17	Illinois CancerCare-Pekin	Pekin	Illinois	United States	61554
18	Illinois CancerCare-Peoria	Peoria	Illinois	United States	61615
19	Illinois CancerCare-Peru	Peru	Illinois	United States	61354
20	Illinois CancerCare-Princeton	Princeton	Illinois	United States	61356
21	West Suburban Medical Center	River Forest	Illinois	United States	60305
22	Southern Illinois University School of Medicine	Springfield	Illinois	United States	62702
23	Springfield Clinic	Springfield	Illinois	United States	62702
24	Illinois CancerCare - Washington	Washington	Illinois	United States	61571
25	Rush-Copley Healthcare Center	Yorkville	Illinois	United States	60560
26	Mary Greeley Medical Center	Ames	Iowa	United States	50010
27	McFarland Clinic PC - Ames	Ames	Iowa	United States	50010
28	McFarland Clinic PC-Boone	Boone	Iowa	United States	50036
29	Oncology Associates at Mercy Medical Center	Cedar Rapids	Iowa	United States	52403
30	Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
31	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa	United States	50309
32	Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
33	McFarland Clinic PC-Trinity Cancer Center	Fort Dodge	Iowa	United States	50501
34	McFarland Clinic PC-Jefferson	Jefferson	Iowa	United States	50129
35	McFarland Clinic PC-Marshalltown	Marshalltown	Iowa	United States	50158
36	Saint Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106
37	IHA Hematology Oncology Consultants-Brighton	Brighton	Michigan	United States	48114
38	Saint Joseph Mercy Brighton	Brighton	Michigan	United States	48114
39	IHA Hematology Oncology Consultants-Canton	Canton	Michigan	United States	48188
40	Saint Joseph Mercy Canton	Canton	Michigan	United States	48188
41	IHA Hematology Oncology Consultants-Chelsea	Chelsea	Michigan	United States	48118
42	Saint Joseph Mercy Chelsea	Chelsea	Michigan	United States	48118
43	Saint Mary Mercy Hospital	Livonia	Michigan	United States	48154
44	Huron Gastroenterology PC	Ypsilanti	Michigan	United States	48106
45	IHA Hematology Oncology Consultants-Ann Arbor	Ypsilanti	Michigan	United States	48197
46	Sanford Joe Lueken Cancer Center	Bemidji	Minnesota	United States	56601
47	Sanford Thief River Falls Medical Center	Thief River Falls	Minnesota	United States	56701
48	Sanford Cancer Center Worthington	Worthington	Minnesota	United States	56187
49	Saint Francis Medical Center	Cape Girardeau	Missouri	United States	63703
50	Parkland Health Center - Farmington	Farmington	Missouri	United States	63640
51	Missouri Baptist Medical Center	Saint Louis	Missouri	United States	63131
52	Mercy Hospital Saint Louis	Saint Louis	Missouri	United States	63141
53	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri	United States	63670
54	Missouri Baptist Sullivan Hospital	Sullivan	Missouri	United States	63080
55	Missouri Baptist Outpatient Center-Sunset Hills	Sunset Hills	Missouri	United States	63127
56	Sanford Bismarck Medical Center	Bismarck	North Dakota	United States	58501
57	Sanford Broadway Medical Center	Fargo	North Dakota	United States	58122
58	Sanford Roger Maris Cancer Center	Fargo	North Dakota	United States	58122
59	Altru Cancer Center	Grand Forks	North Dakota	United States	58201
60	Prisma Health Cancer Institute - Spartanburg	Boiling Springs	South Carolina	United States	29316
61	Prisma Health Cancer Institute - Easley	Easley	South Carolina	United States	29640
62	Prisma Health Cancer Institute - Butternut	Greenville	South Carolina	United States	29605
63	Prisma Health Cancer Institute - Faris	Greenville	South Carolina	United States	29605
64	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina	United States	29615
65	Prisma Health Cancer Institute - Greer	Greer	South Carolina	United States	29650
66	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina	United States	29672
67	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota	United States	57104
68	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota	United States	57117-5134

Sponsors and Collaborators

Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)

Investigators

Study Chair: Aminah Jatoi, MD, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Alliance for Clinical Trials in Oncology

ClinicalTrials.gov Identifier:

NCT04939090

Other Study ID Numbers:

A222004
NCI-2021-03303
UG1CA189823

First Posted:

Jun 25, 2021

Last Update Posted:

Jan 13, 2022

Last Verified:

Jan 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Study Results

No Results Posted as of Jan 13, 2022