Olanzapine vs Megestrol Acetate for Cancer-Related Anorexia

Recruiting at 276 trial locations

Overseen By Steven E. Sckolnik

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Alliance for Clinical Trials in Oncology

Must not be taking: Antipsychotics, Appetite stimulants

Disqualifiers: Uncontrolled infection, Diabetes, Cardiac disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

360 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests whether olanzapine or megestrol acetate is better at increasing appetite in patients with advanced cancer. These patients often struggle with eating and weight loss. Both medications aim to make them feel hungrier, helping them eat more and gain weight. Megestrol acetate is known for its effectiveness in increasing appetite in patients with cancer.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use certain medications like systemic adrenal steroids, androgens, progesterone analogs, or other appetite stimulants within the past month. You also cannot be on other antipsychotic medications like risperidone or quetiapine within 30 days of enrollment.

What data supports the effectiveness of the drugs olanzapine and megestrol acetate for cancer-related anorexia?

Research shows that megestrol acetate can improve appetite and lead to weight gain in patients with cancer-related anorexia. Additionally, olanzapine has been found to stimulate appetite and improve weight gain in patients undergoing chemotherapy. ^{1 2 3 4 5}

Is the combination of Olanzapine and Megestrol Acetate safe for treating cancer-related anorexia?

Megestrol Acetate is generally well-tolerated but has a clear risk of blood clots, especially at higher doses. Olanzapine is not specifically mentioned in the safety data provided, but it is commonly used for other conditions and generally considered safe with known side effects like weight gain and drowsiness. ^{2 3 5 6 7}

How does the drug olanzapine differ from other treatments for cancer-related anorexia?

Olanzapine is unique in treating cancer-related anorexia because it is primarily an antipsychotic medication, which may help improve appetite by affecting brain chemicals differently than traditional treatments like megestrol acetate, a hormone derivative. This novel approach could offer an alternative for patients who do not respond well to existing options. ^{2 3 5 7 8}

Research Team

Aminah Jatoi, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

Adults with advanced cancer experiencing loss of appetite or weight loss, who haven't used olanzapine for other conditions or certain appetite stimulants recently. Participants must not have severe diabetes, heart failure, hypertension, a history of blood clots, brain metastases causing symptoms, digestive obstructions or persistent vomiting. They should be able to swallow pills and not have infections like HIV that could complicate the trial.

Inclusion Criteria

I can speak and/or read English or Spanish.

I am not pregnant or nursing and, if capable of becoming pregnant, I have a recent negative pregnancy test.

I do not have brain metastases or leptomeningeal disease.

Exclusion Criteria

I am capable of making my own health decisions.

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either olanzapine or megestrol acetate orally once daily for up to 4 weeks

4 weeks

Weekly assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Megestrol Acetate
• Olanzapine

Trial Overview This phase III trial is testing whether olanzapine is more effective than megestrol acetate in increasing appetite and preventing weight loss in patients with advanced cancer. Patients will either receive olanzapine or megestrol acetate and their appetites will be monitored through questionnaires.

Participant Groups

Group I: Arm I (olanzapine) Experimental Treatment 2 Interventions

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

Group II: Arm II (megestrol acetate) Active Control 2 Interventions

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

Olanzapine is already approved in United States, European Union for the following indications:

Approved in United States as Zyprexa for:

• Schizophrenia
• Bipolar disorder
• Depression
• Nausea and vomiting associated with chemotherapy
• Off-label use for cancer cachexia and anorexia

Approved in European Union as Zyprexa for:

• Schizophrenia
• Bipolar disorder
• Depression
• Nausea and vomiting associated with chemotherapy

Who Is Running the Clinical Trial?

Alliance for Clinical Trials in Oncology

Lead Sponsor

Trials

521

Recruited

224,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 124 patients with advanced cancers receiving chemotherapy, those treated with low-dose olanzapine showed a significant increase in weight gain (>5%) compared to the placebo group (60% vs. 9%).

Olanzapine also improved appetite and quality of life, with minimal side effects, making it a safe and effective option for managing anorexia in cancer patients undergoing chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Double-Blind Placebo-Controlled Study of Olanzapine for Chemotherapy-Related Anorexia in Patients With Locally Advanced or Metastatic Gastric, Hepatopancreaticobiliary, and Lung Cancer. Sandhya, L., Devi Sreenivasan, N., Goenka, L., et al.[2023]

In a study of 80 patients with advanced gastrointestinal or lung cancer, the combination of megestrol acetate (MA) and olanzapine (OLN) significantly improved weight gain and appetite compared to MA alone, with 33 out of 39 patients in the combination group gaining at least 5% of their weight.

Both treatments were well-tolerated, with no severe treatment-related toxicities reported, indicating that the combination therapy is a safe and effective option for managing cancer-related anorexia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of cancer-related anorexia with olanzapine and megestrol acetate: a randomized trial. Navari, RM., Brenner, MC.[2022]

In a study of 28 breast cancer patients treated with high doses of oral megestrol acetate (480 to 1600 mg/d), 27 patients experienced significant weight gain (median of 5.1 kg), indicating its potential effectiveness in addressing weight loss and anorexia associated with cancer.

The weight gain occurred regardless of factors like initial weight or extent of disease, suggesting that megestrol acetate may improve the quality of life for patients suffering from cachexia, although further research is needed to understand its mechanism and clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose megestrol acetate. A possible treatment for cachexia. Tchekmedyian, NS., Tait, N., Moody, M., et al.[2016]

Megestrol acetate has been shown to improve appetite and food intake in patients with anorexia due to advanced cancer, leading to weight gain in some individuals, based on results from randomized, placebo-controlled trials.

The drug likely works through both behavioral and metabolic mechanisms, and ongoing trials aim to determine the optimal dosage and further clarify how it promotes weight gain in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of anorexia and weight loss with megestrol acetate in patients with cancer or acquired immunodeficiency syndrome. Tchekmedyian, NS., Hickman, M., Heber, D.[2018]

Megestrol acetate has been observed to effectively increase appetite and promote weight gain in patients with advanced cancer, making it a potential palliative treatment for cancer-related anorexia.

Numerous clinical trials have been conducted to evaluate the efficacy of megestrol acetate in addressing the anorexia and weight loss syndrome associated with cancer, providing a basis for its practical use in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Megestrol acetate for the palliation of anorexia in advanced, incurable cancer patients. Mateen, F., Jatoi, A.[2013]

A meta-analysis of 23 clinical trials found that megestrol acetate (MA) did not significantly improve weight in cancer patients with anorexia/cachexia, with an overall mean weight change of only 0.75 kg, indicating limited efficacy.

While MA was generally well-tolerated, it posed a clear risk of thromboembolic events, particularly at higher doses, highlighting safety concerns associated with its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review and Meta-Analysis of the Clinical Use of Megestrol Acetate for Cancer-Related Anorexia/Cachexia. Lim, YL., Teoh, SE., Yaow, CYL., et al.[2023]

Megestrol acetate (MA) has been shown to significantly improve appetite and promote weight gain in cancer patients, based on a review of 30 trials involving 4123 participants.

However, the evidence for its effectiveness in patients with AIDS or other conditions is inconclusive due to methodological issues and insufficient data, preventing a clear recommendation for those populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Megestrol acetate for the treatment of anorexia-cachexia syndrome. Berenstein, EG., Ortiz, Z.[2018]

Megestrol acetate has been shown to effectively increase appetite, food intake, and weight in patients with advanced cancers and AIDS, based on randomized, placebo-controlled trials.

While megestrol acetate is generally well tolerated and may improve symptoms of anorexia and weight loss, it has not been shown to significantly impact survival rates in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of anorexia with megestrol acetate. Tchekmedyian, NS.[2017]

References

1. United States pubmed.ncbi.nlm.nih.gov

Randomized Double-Blind Placebo-Controlled Study of Olanzapine for Chemotherapy-Related Anorexia in Patients With Locally Advanced or Metastatic Gastric, Hepatopancreaticobiliary, and Lung Cancer. [2023]

2. Germany pubmed.ncbi.nlm.nih.gov

Treatment of cancer-related anorexia with olanzapine and megestrol acetate: a randomized trial. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

High-dose megestrol acetate. A possible treatment for cachexia. [2016]

4. United States pubmed.ncbi.nlm.nih.gov

Treatment of anorexia and weight loss with megestrol acetate in patients with cancer or acquired immunodeficiency syndrome. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Megestrol acetate for the palliation of anorexia in advanced, incurable cancer patients. [2013]

6. Switzerland pubmed.ncbi.nlm.nih.gov

A Systematic Review and Meta-Analysis of the Clinical Use of Megestrol Acetate for Cancer-Related Anorexia/Cachexia. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Megestrol acetate for the treatment of anorexia-cachexia syndrome. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Treatment of anorexia with megestrol acetate. [2017]