Olanzapine vs Megestrol Acetate for Cancer-Related Anorexia

Recruiting at 314 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether olanzapine (Zyprexa) is more effective than megestrol acetate (Megace) in boosting appetite in people with advanced cancer. Olanzapine may help increase appetite and prevent weight loss. Participants will receive one of these treatments for up to four weeks. Those who have lost at least 5 pounds in the last two months and find their loss of appetite problematic might be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that olanzapine is generally well-tolerated by patients. Some studies indicate that even at low doses, like 2.5 mg daily, it can significantly help cancer patients gain weight. One study found that olanzapine's side effects were similar to those of a placebo, suggesting it is quite safe.

For megestrol acetate, evidence shows it can also help cancer patients gain weight. However, it might not improve appetite or quality of life as much as expected. Interestingly, research has found no significant difference in side effects when using megestrol acetate compared to not using it, suggesting that side effects are not a major concern with this treatment.

Both treatments are under study to assess their effectiveness for cancer-related appetite loss. Current research suggests both have a good safety profile. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for cancer-related anorexia, like megestrol acetate, work by stimulating appetite. However, olanzapine is unique because it targets the brain's neurotransmitters, potentially addressing both appetite and the psychological components of anorexia, such as anxiety or nausea. Researchers are excited about olanzapine because it offers a dual-action approach, which might provide more comprehensive symptom relief compared to standard appetite stimulants.

What evidence suggests that this trial's treatments could be effective for cancer-related anorexia?

Research has shown that olanzapine, one of the treatments in this trial, can help increase appetite in patients with incurable cancer. Studies have found that even small doses, like 2.5 mg daily, lead to noticeable weight gain and improved appetite. Specifically, one study found that taking 5 mg daily for a short time significantly reduced loss of appetite in patients with cancer and weight loss. Overall, olanzapine appears promising in boosting appetite and helping cancer patients gain weight. Meanwhile, researchers are also studying megestrol acetate, the other treatment option in this trial, for its effects on cancer-related anorexia. ^{6 7 8 9 10}

Who Is on the Research Team?

Aminah Jatoi, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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 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]

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 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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40738139/

Olanzapine for Anorexia in Patients With Incurable Cancer ... Conclusions: A short course of olanzapine 5 mg daily significantly reduces anorexia in patients with incurable cancer and cachexia. Further ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10893239/

A Review of Olanzapine in the Treatment of Cancer ... Olanzapine doses as low as 2.5 mg once daily have been shown to produce significant weight gain in a randomized controlled trial.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06517199

Olanzapine for Cancer Related Anorexia-cachexia Syndrome Olanzapine has been demonstrated to reduce chemotherapy-induced anorexia. However, there is scarce information regarding olanzapine as a treatment of cancer ...

4. jnccn.org jnccn.org/view/journals/jnccn/23/9/article-p385.xml?print

Olanzapine for Anorexia in Patients With Incurable Cancer ... In that study, olanzapine 2.5 mg daily for 12 weeks resulted in significant improvement of chemotherapy-associated anorexia and weight gain.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05243251

NCT05243251 | Olanzapine Anorexia Cachexia Primary outcome. o Change in loss of appetite score from day 0 to day 7 of treatment with olanzapine 5 mg orally once daily at night: on the loss of appetite ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9267332/

A Systematic Review and Meta-Analysis of the Clinical Use of ... The present meta-analysis provides us with greater surety in recommending against the use of megestrol acetate for the symptomatic improvement of anorexia/ ...

7. mypcnow.org mypcnow.org/fast-fact/megestrol-acetate-for-cancer-anorexia-cachexia/?print=print

Megestrol Acetate for Cancer Anorexia/Cachexia Outcome Data Overall, data suggests that approximately one in four patients ... megestrol acetate for patients with cancer-related anorexia/cachexia syndrome.

8. ascopubs.org ascopubs.org/doi/10.1200/jco.2008.26.15_suppl.9576

Treatment of cancer-related anorexia with olanzapine and ... The use of megestrol acetate (MA) has resulted in weight gain in some CRA patients, but MA has had less effect on improving appetite and quality of life (QOL).

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5989756/

Megestrol acetate for cachexia–anorexia syndrome. A ... We found two trials with 101 cancer participants.28 , 46 The results showed no differences in adverse events (RR 0.90, 95% CI [0.39, 2.08]). We judged the ...

10. clinicaltrials.gov clinicaltrials.gov/study/NCT00637806?intr=%22Megestrol%22&viewType=Table&rank=9

Treatment of Cancer-associated Anorexia Using Megestrol ... Fair, poor, or very poor appetite. Cancer-associated anorexia/cachexia (documented weight loss of 2% over the prior week, or at least 5% within past 30 days, ...