Megestrol Acetate + Pterostilbene for Endometrial Cancer

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Must not be taking: Pterostilbene, Resveratrol

Disqualifiers: Unstable cardiac disease, Thromboembolism, HIV, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 3 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of megestrol acetate, alone or combined with pterostilbene, in treating endometrial cancer in patients undergoing a hysterectomy. Megestrol acetate, a chemotherapy drug, can inhibit tumor cell growth. Pterostilbene, an antioxidant found in foods like blueberries, might help reduce cancer. The trial includes two groups: one receiving only megestrol acetate and the other receiving both megestrol acetate and pterostilbene. It is suitable for women with confirmed endometrial cancer or complex atypical hyperplasia who plan to have a hysterectomy. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Do I need to stop taking my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot take certain supplements like pterostilbene, resveratrol, genistein, and quercetin within 30 days before starting the trial. It's best to discuss your current medications with the trial team to be sure.

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

Research shows that megestrol acetate is generally well-tolerated by patients. Studies indicate that more than half of the patients treated with megestrol acetate for endometrial cancer survived two years after starting treatment, and about a third experienced no worsening of their disease. These findings suggest that the drug is safe for many people.

Pterostilbene, a compound found in blueberries and grapes, is still under investigation for its safety when used with megestrol acetate. Some research shows that this combination can effectively kill cancer cells and slow their growth. However, since pterostilbene is not yet approved for this use, its safety in humans remains unclear.

This trial is in its second phase, indicating that understanding the safety of the pterostilbene-megestrol acetate combination is still in the early stages. More data is needed to confirm how well people tolerate it, but current studies are promising. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of megestrol acetate and pterostilbene for endometrial cancer because it offers a novel approach to treatment. Unlike standard hormonal therapies that primarily involve progesterone analogs like megestrol acetate alone, this treatment adds pterostilbene, a compound found in blueberries with potential anti-cancer properties. Pterostilbene is thought to boost the effectiveness of megestrol acetate by enhancing its ability to inhibit cancer cell growth. This dual-action strategy could potentially lead to more effective management of endometrial cancer, especially for patients who might not respond well to existing hormonal therapies.

What evidence suggests that this trial's treatments could be effective for endometrial cancer?

Studies have shown that megestrol acetate, which participants in this trial may receive, can help treat endometrial cancer, with 20-85% of patients experiencing tumor shrinkage or halted growth. Another treatment arm in this trial adds pterostilbene, a natural antioxidant found in blueberries, to megestrol acetate, potentially enhancing its effectiveness. Research suggests that this combination can reduce cancer cell growth and survival. Additionally, pterostilbene may boost the immune system's ability to fight cancer. These findings indicate that using both megestrol acetate and pterostilbene could be a promising treatment option for endometrial cancer patients. ^{4 6 7 8 9}

Who Is on the Research Team?

Thanh H. Dellinger

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for women with endometrial cancer or complex atypical hyperplasia who are fit enough for surgery (ECOG 0-2) and have normal liver and kidney function. They must be able to swallow pills, not pregnant, without serious heart conditions, infections needing IV treatment, HIV, hepatitis B/C, recent thromboembolism/stroke/MI or taking certain supplements.

Inclusion Criteria

Platelets >= 100,000/mm^3

I am a candidate for a surgery to remove my uterus, and possibly my ovaries and fallopian tubes.

Total bilirubin =< 1.5 X upper limit of normal (ULN)

Exclusion Criteria

Allergic reaction/hypersensitivity to similar agents, excipients

Unstable cardiac disease as defined by one of the following: cardiac events such as myocardial infarction (MI) within the past 6 months, NYHA (New York Heart Association) heart failure class III-IV, uncontrolled atrial fibrillation or hypertensive emergency/urgency (defined as systolic blood pressure >= 180 mmHg and/or diastolic blood pressure >= 120 mmHg), active or history of recent thromboembolism or stroke, within the past 6 months, Cushing's syndrome, acute infection requiring systemic (intravenous) treatment, known history of human immunodeficiency virus (HIV) infection, known active hepatitis B or C infection, inability to swallow tablets/capsules, any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures, e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, social/ psychological issues, etc, prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

I have not taken pterostilbene supplements in the last 30 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive megestrol acetate with or without pterostilbene for 3 weeks

3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Megestrol Acetate
• Pterostilbene

Trial Overview The study is testing the effectiveness of megestrol acetate (a chemotherapy drug) with or without pterostilbene (an antioxidant found in blueberries/grapes) in patients undergoing hysterectomy for endometrial cancer. It aims to determine if adding pterostilbene improves outcomes.

How Is the Trial Designed?

Group I: Arm II (megestrol acetate) Experimental Treatment 1 Intervention

Patients receive megestrol acetate PO BID for 3 weeks in the absence of disease progression or unaccepted toxicity.

Group II: Arm I (pterostilbene, megestrol acetate) Experimental Treatment 2 Interventions

Patients receive pterostilbene PO BID and megestrol acetate PO BID for 3 weeks in the absence of disease progression or unaccepted toxicity.

Megestrol Acetate is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Megace for:

• Breast cancer
• Endometrial cancer
• Prostate cancer
• Appetite stimulation

Approved in European Union as Megestrol for:

• Breast cancer
• Endometrial cancer
• Prostate cancer
• Appetite stimulation

Approved in Canada as Megace for:

• Breast cancer
• Endometrial cancer
• Prostate cancer
• Appetite stimulation

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/19396003/

Efficacy of megestrol acetate (megace) in the treatment of ... Results: Our results showed a response rate of 85.71% (18 patients), and 3 patients underwent hysterectomy. The mean (SD) treatment duration was 8.85 (2.00) ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.5585

Outcomes of recurrent and metastatic endometrial cancer ... Overall response rates have been reported in the range of 20-25% with responses up to 25-35% in ER+/PR+ve tumors. Despite comparative response ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1048891X24026781

Efficacy of Megestrol Acetate (Megace) in the Treatment ... Results: Our results showed a response rate of 85.71% (18 patients), and 3 patients underwent hysterectomy. The mean (SD) treatment duration was 8.85 (2.00) ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04576104

Study Details | NCT04576104 | Megestrol Acetate ... This phase II trial studies the effect of megestrol acetate alone or in combination with metformin in preventing the progression of uterine pre-cancer ...

5. international-journal-of-gynecological-cancer.com international-journal-of-gynecological-cancer.com/article/S1048-891X(24)02678-1/pdf

Efficacy of Megestrol Acetate (Megace) in the Treatment of ... Conservative therapy for adenocarcinoma and atypical endometrial hyperplasia of the endometrium in young women: central pathologic review and treatment outcome.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8581832/

Megestrol acetate drives endometrial carcinoma cell ... This study demonstrates that megestrol acetate could induce irreversible G1 arrest and cellular senescence, affect the survival and growth of endometrial cancer ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12531510/

Enhanced efficacy and safety of combining Aidi injection with ... The combination of Aidi injection and megestrol acetate demonstrates significant clinical efficacy in treating endometrial cancer by synergistically inhibiting ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S1048891X24043470

A Phase 2, Randomized, Open-Label Study of Irosustat ... More than 50% of patients were alive and 31% progressionfree 2 years after the start of treatment with megestrol acetate. This response rate is higher than ...

9. obgyn.onlinelibrary.wiley.com obgyn.onlinelibrary.wiley.com/doi/10.1111/aogs.70028

Long‐term outcomes of fertility‐sparing treatment in ... Fertility-sparing treatment demonstrated a 62.5% recurrence rate at 10 years. Recurrence was more likely in patients initially treated with ...