Fisetin for Breast Cancer Survivors

Recruiting at 8 trial locations

Overseen By Mina S. Sedrak

Age: Any Age

Sex: Female

Trial Phase: Phase 2

Sponsor: Jonsson Comprehensive Cancer Center

Must not be taking: Senolytics, Anticoagulants, Herbal supplements

Disqualifiers: Active cancer, Surgery, Radiation, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

88 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether fisetin, a natural substance in strawberries, can improve physical function in women recovering from chemotherapy for stage I-III breast cancer. Chemotherapy can cause cells to age and stop dividing, leading to inflammation and harm to other healthy cells. Fisetin might help remove these aged cells, possibly enhancing physical ability. Women who are postmenopausal, have undergone chemotherapy for early-stage breast cancer in the past year, and experience frailty (such as difficulty walking) might be suitable for this trial. Participants will receive either fisetin or a placebo to compare outcomes. As a Phase 2 trial, this research focuses on measuring fisetin's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

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

The trial protocol does not specify if you must stop all current medications. However, you cannot take certain medications with senolytic properties like curcumin or St. John's wort during the trial. Some medications may need to be withheld temporarily during dosing intervals. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that fisetin is likely to be safe for humans?

Research has shown that fisetin, a natural substance found in strawberries and other foods, is generally safe for humans. Studies have found that fisetin offers several benefits, such as reducing inflammation and acting as an antioxidant. It may also help fight cancer.

In cancer-focused trials, researchers have used fisetin without major safety issues. Available studies report no serious side effects linked to fisetin, suggesting it is safe for humans, especially since it comes from natural sources.

Researchers are currently studying fisetin in a trial to see if it can improve physical function in breast cancer survivors. Its presence in a Phase 2 trial indicates that earlier trials found it safe enough to continue studying its benefits. This phase usually focuses more on efficacy, as safety has already been assessed.

Overall, fisetin appears to be a promising and safe option for those considering alternative treatments after chemotherapy. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for breast cancer survivors?

Unlike the standard treatments for breast cancer survivors, which often include hormone therapy, chemotherapy, and radiation, fisetin offers a unique approach. Fisetin is a natural flavonoid found in many fruits and vegetables, known for its antioxidant and anti-inflammatory properties. Researchers are excited about its potential because it might offer a gentler alternative by targeting inflammation and oxidative stress, which are linked to cancer progression, without the harsh side effects typical of conventional therapies. This treatment could provide a novel way to support breast cancer survivors in maintaining their health and preventing recurrence.

What evidence suggests that fisetin might be an effective treatment for improving physical function in breast cancer survivors?

Research has shown that fisetin, a natural substance found in strawberries, offers several health benefits. It possesses antioxidant and anti-inflammatory properties, which can help combat cancer and other diseases. Notably, fisetin can remove senescent cells—old cells that stop dividing but don't die. These cells can accumulate after chemotherapy, causing inflammation and harming healthy cells. Studies have demonstrated that fisetin can reduce the number of these harmful cells, potentially improving physical function in breast cancer survivors. In this trial, participants in Arm A will receive fisetin, while those in Arm B will receive a placebo. Early findings suggest fisetin may enhance physical well-being in individuals who have undergone chemotherapy. ^{1 3 4 6 7}

Who Is on the Research Team?

Mina S. Sedrak

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for postmenopausal women aged 65 or older who have had stage I-III breast cancer treated with chemotherapy within the last year. Participants must be able to walk on their own, even if they use a cane or walker, but have a reduced walking ability (less than 400m in 6 minutes). They should not have had surgery or radiation in the past month and must agree to stop certain natural medications before and during the study.

Inclusion Criteria

I am female.

I finished my chemotherapy less than a year ago.

I was 65 or older when my cancer was diagnosed.

Exclusion Criteria

I am taking herbal medications but can stop them 2 days before and during the study, except for CBD, vitamin C, and D.

I haven't had surgery or radiation in the last 30 days, except for minor procedures like a biopsy.

I have trouble taking pills due to conditions like difficulty swallowing or ongoing nausea.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive fisetin or placebo orally on days 1, 2, and 3, with treatment repeating every 2 weeks for up to 8 weeks. Blood samples are collected throughout the trial.

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up occurring yearly for up to 3 years.

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Fisetin

Trial Overview The TROFFi trial is testing fisetin, a substance found in strawberries that might remove aging cells built up from chemotherapy, which could improve physical function. Women will either receive fisetin or a placebo while also undergoing quality-of-life assessments through questionnaires and biospecimen collection.

How Is the Trial Designed?

Group I: Arm A (fisetin) Experimental Treatment 4 Interventions

Patients receive fisetin PO on days 1, 2, and 3. Treatment repeats every 2 weeks for up to 8 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples throughout the trial.

Group II: Arm B (placebo) Placebo Group 4 Interventions

Patients receive placebo PO on the trial. on days 1, 2, and 3. Treatment repeats every 2 weeks for up to 8 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples throughout the trial.

Who Is Running the Clinical Trial?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

The combination of quercetin/fisetin with naringenin showed a synergistic effect in reducing cell growth and migration in breast cancer cell lines (MCF7 and MDA-MB-231), indicating enhanced anti-cancer properties compared to using these flavonoids individually.

Gene expression analysis revealed that this combination therapy upregulated the tumor suppressor miR-1275 and downregulated the oncogenic miR-27a-3p, suggesting a mechanism of action that promotes apoptosis and inhibits cancer cell proliferation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naringenin in combination with quercetin/fisetin shows synergistic anti-proliferative and migration reduction effects in breast cancer cell lines. Jalalpour Choupanan, M., Shahbazi, S., Reiisi, S.[2023]

Fisetin, a natural flavonoid, showed significant cytotoxic effects on breast cancer cells (MCF-7) while sparing non-cancerous cells (MCF-10A), indicating its potential as a targeted cancer treatment.

The study revealed that fisetin induces a unique form of apoptosis in MCF-7 cells that does not rely on traditional pathways, suggesting it could be an effective new approach for treating breast cancer, especially in cases resistant to conventional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary flavonoid fisetin targets caspase-3-deficient human breast cancer MCF-7 cells by induction of caspase-7-associated apoptosis and inhibition of autophagy. Yang, PM., Tseng, HH., Peng, CW., et al.[2021]

Fisetin has been shown to enhance the effectiveness of radiation therapy in p53-mutant HT-29 human colorectal cancer cells, which are typically resistant to such treatments, indicating its potential as a radiosensitizer.

The study demonstrated that fisetin pretreatment not only increased radiation-induced apoptosis in these cancer cells but also affected key signaling pathways, suggesting a mechanism by which fisetin enhances radiosensitivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhancement of p53-mutant human colorectal cancer cells radiosensitivity by flavonoid fisetin. Chen, WS., Lee, YJ., Yu, YC., et al.[2021]

Fisetin, a flavonol found in various fruits and vegetables, has demonstrated the ability to inhibit cancer cell growth in laboratory studies and in animal models, suggesting its potential as a cancer treatment.

The compound works by targeting key components of cell signaling pathways that regulate cell survival, apoptosis, and tumor growth, highlighting its multifaceted mechanism of action in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The flavonoid fisetin as an anticancer agent targeting the growth signaling pathways. Rengarajan, T., Yaacob, NS.[2021]

Fisetin, a natural flavonoid found in fruits and vegetables, shows promising anticancer effects against female malignancies such as breast, cervical, and ovarian cancer, based on both in vitro and in vivo studies.

The compound has low toxicity and potential for use in cancer treatment, but further large-scale clinical trials are necessary to confirm its effectiveness as a chemotherapeutic agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of Fisetin in Selected Malignant Neoplasms in Women. Markowska, A., Antoszczak, M., Kacprzak, K., et al.[2023]

Fisetin, a natural flavonoid, effectively inhibits cell proliferation, migration, and invasion in triple negative breast cancer (TNBC) cell lines, suggesting its potential as a therapeutic agent against this aggressive cancer type.

The anti-metastatic effects of fisetin are linked to its ability to reverse epithelial to mesenchymal transition (EMT) and modulate the PTEN/Akt/GSK-3β signaling pathway, as demonstrated in both in vitro and in vivo models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fisetin Inhibited Growth and Metastasis of Triple-Negative Breast Cancer by Reversing Epithelial-to-Mesenchymal Transition via PTEN/Akt/GSK3β Signal Pathway. Li, J., Gong, X., Jiang, R., et al.[2020]

Fisetin effectively inhibited the growth of triple-negative breast cancer (TNBC) cells, specifically MDA-MB-468 and MDA-MB-231, while sparing non-malignant cells, indicating its potential as a targeted treatment option.

The mechanism of action involves inducing apoptosis in TNBC cells through mitochondrial membrane permeabilization and activation of caspases, along with inhibition of Aurora B kinase, suggesting that fisetin could enhance the effectiveness of existing chemotherapy agents like cisplatin and 5-fluorouracil.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Dietary Flavonoid Fisetin Causes Cell Cycle Arrest, Caspase-Dependent Apoptosis, and Enhanced Cytotoxicity of Chemotherapeutic Drugs in Triple-Negative Breast Cancer Cells. Smith, ML., Murphy, K., Doucette, CD., et al.[2021]

Fisetin, a natural compound found in fruits and vegetables, significantly inhibits the growth and DNA synthesis of human colon cancer cells (HT-29), with a 79% reduction in cell number observed after 72 hours at a concentration of 60 micromol/L.

The mechanism of action involves disrupting cell cycle progression, particularly causing a G(1) to S phase arrest and a G(2)/M phase block, which is linked to decreased activity of cyclin-dependent kinases (CDK) and changes in retinoblastoma protein phosphorylation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fisetin inhibits the activities of cyclin-dependent kinases leading to cell cycle arrest in HT-29 human colon cancer cells. Lu, X., Jung, Ji., Cho, HJ., et al.[2023]

In a murine xenograft model, fisetin significantly suppressed the growth of CT-26 colon cancer tumors when injected directly, but had minimal effect on HCT116 tumors, indicating its selective efficacy.

When combined with radiation, fisetin enhanced tumor suppression in both murine and human colorectal cancer models, suggesting it could be a valuable adjuvant in chemoradiotherapy, particularly through its ability to downregulate the oncoprotein securin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining fisetin and ionizing radiation suppresses the growth of mammalian colorectal cancers in xenograft tumor models. Leu, JD., Wang, BS., Chiu, SJ., et al.[2020]

Fisetin, a natural polyphenolic compound, shows promise in blocking multiple signaling pathways related to chronic diseases, including cancer, by targeting processes like cell division and inflammation.

Research is ongoing to improve the bioavailability of fisetin when taken orally, which could enhance its effectiveness in preventing and treating various cancers, such as those of the liver, breast, and ovary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fisetin: A bioactive phytochemical with potential for cancer prevention and pharmacotherapy. Kashyap, D., Sharma, A., Sak, K., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05595499?cond=fisetin&aggFilters=status:&viewType=Table&rank=10

Fisetin to Improve Physical Function in Stage I-III Breast ... This phase II trial tests whether fisetin works to improve physical function in women who have received chemotherapy for stage I-III breast ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9961076/

Fisetin in Cancer: Attributes, Developmental Aspects, and ... Fisetin is one such naturally derived flavone that offers numerous pharmacological benefits, ie, antioxidant, anti-inflammatory, antiangiogenic, and anticancer ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06113016

Prevention of Frailty With Fisetin and Exercise in Breast ... This phase II trial tests how well fisetin and exercise works in preventing frailty in breast cancer survivors. Fisetin is a natural substance found in ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10648688/

Role of Fisetin in Selected Malignant Neoplasms in Women In this review, we have summarized the results of studies on the anticancer effects of fisetin on selected female malignancies, both in in vitro and in vivo ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0047637424000952

Fisetin as a senotherapeutic agent: Evidence and ... Fisetin reduced the viability and number of senescent cells in other cell types, including rat NRK-52E rat tubular epithelial cells (Ijima et al., 2022) and ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3689181/

Fisetin: A Dietary Antioxidant for Health Promotion - PMC Dietary flavonoid fisetin targets caspase-3-deficient human breast cancer MCF-7 cells by induction of caspase-7-associated apoptosis and inhibition of ...

7. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/433176

Prevention of Frailty With Fisetin and Exercise in Breast ... 3,3',4',7-tetrahydroxyflavone ... This phase II trial tests how well fisetin and exercise works in preventing frailty in breast cancer survivors.