Fisetin + Exercise for Breast Cancer

(PROFFi Trial)

Recruiting at 5 trial locations

Overseen By Kelly Synold

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

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: 5

Duration: 16 weeks

164 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether fisetin, a natural supplement found in strawberries, combined with exercise, can prevent frailty in breast cancer survivors. Fisetin may help remove old cells that stop dividing but don't die, which can otherwise cause harm. Participants will either take fisetin or a placebo and follow an exercise plan to determine which approach is most effective. Women who have completed treatment for early-stage breast cancer and feel less energetic might be suitable for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, providing participants an opportunity to contribute to important findings.

Will I have to stop taking my current medications?

The trial requires you to stop taking certain medications, especially those with senolytic properties like curcumin or St. John's wort, 2 days before and during the study. Some medications may need to be temporarily adjusted, and others are prohibited, so it's best to discuss your current medications with the study team.

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

Research has shown that fisetin, a natural substance found in strawberries and other foods, is generally safe for people. Studies indicate that fisetin offers health benefits by reducing inflammation and acting as an antioxidant. Although researchers are still studying fisetin's effects on cancer patients, it has shown potential in reducing inflammation without significant side effects.

Exercise, the other part of the trial, is well-known for its safety and benefits, especially for breast cancer survivors. Regular physical activity can lower the risk of cancer recurrence and improve quality of life. It also enhances overall well-being and fitness.

This trial explores whether combining fisetin and exercise can help prevent frailty in breast cancer survivors. Current research suggests that these treatments are safe, with minimal risks for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for breast cancer because they combine fisetin, a natural compound found in fruits like strawberries, with exercise to potentially enhance cancer treatment. Unlike standard treatments that primarily focus on chemotherapy or hormonal therapy, this approach leverages the anti-inflammatory and antioxidant properties of fisetin, which may help inhibit cancer growth. Additionally, the inclusion of tailored exercise programs could improve overall patient health, reduce treatment side effects, and boost the immune system, offering a holistic approach to cancer care. This combination aims to provide a dual benefit by directly targeting cancer cells and strengthening the body's natural defenses.

What evidence suggests that this trial's treatments could be effective for preventing frailty in breast cancer survivors?

Research shows that fisetin, a natural substance in strawberries, may help fight cancer cells. It reduces harmful cell activity and inflammation. Studies have also found that it might slow cancer cell growth and help destroy them. In this trial, some participants will receive fisetin with a physical activity handout, while others will receive fisetin combined with tailored exercise training.

Exercise greatly benefits cancer survivors by improving their quality of life, physical abilities, and energy levels. Regular physical activity is linked to lower chances of cancer returning and reduced death rates in breast cancer patients. In this trial, some participants will receive tailored exercise training with either fisetin or a placebo, while others will receive a physical activity handout with either fisetin or a placebo. Combining fisetin with exercise might enhance these benefits and help reduce frailty in survivors. ^{3 6 7 8 9}

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 who have had early-stage breast cancer treated with chemotherapy within the last year. They should be in a pre-frail state but without active cancer or serious chronic illnesses. Participants must be able to swallow pills, not on certain medications, and not involved in other similar studies.

Inclusion Criteria

I am a woman treated for early-stage breast cancer with chemotherapy in the last 12 months.

I don't have active breast cancer or other serious long-term illnesses.

I can walk between 400 to 480 meters in 6 minutes.

Exclusion Criteria

I am not taking any medications that are not allowed in the study.

I am taking herbal medications that I cannot stop for the study, except for CBD, vitamins, probiotics, and fish oil.

I am on blood thinners like warfarin or heparin.

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 1-3 of each cycle, with treatment repeating every 14 days for 8 cycles. Exercise training or physical activity handouts are provided depending on the arm.

16 weeks

3 visits per week for exercise training (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up visits on days 120 and 180, and then annually for up to 3 years.

3 years

2 visits (in-person) initially, then annual visits

What Are the Treatments Tested in This Trial?

Interventions

• Exercise Intervention
• Fisetin

Trial Overview

The PROFFi trial is testing if fisetin (a natural substance) combined with exercise can prevent frailty in breast cancer survivors by eliminating aged cells that may damage healthy ones. The study includes physical tests, biospecimen collection, educational sessions, and quality-of-life assessments.

How Is the Trial Designed?

Group I: Arm AB (fisetin, tailored exercise training) Experimental Treatment 6 Interventions

Patients receive fisetin PO on days 1-3 of each cycle. Treatment repeats every 14 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive individually tailored supervised exercise training consisting of 30-45 minutes of aerobic training and 20-30 minutes of resistance training three times a week over 16 weeks. Patients undergo collection of blood samples on study.

Group II: Arm A (fisetin, physical activity handout) Active Control 6 Interventions

Patients receive fisetin PO on days 1-3 of each cycle. Treatment repeats every 14 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive handout on the importance of physical activity during baseline. Patients undergo collection of blood samples on study.

Group III: Arm B (placebo, tailored exercise training) Active Control 6 Interventions

Patients receive placebo PO on days 1-3 of each cycle. Treatment repeats every 14 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive individually tailored supervised exercise training consisting of 30-45 minutes of aerobic training and 20-30 minutes of resistance training three times a week over 16 weeks. Patients undergo collection of blood samples on study.

Group IV: Arm C (placebo, physical activity handout) Active Control 6 Interventions

Patients receive placebo PO on days 1-3 of each cycle. Treatment repeats every 14 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive handout on the importance of physical activity during baseline. Patients undergo collection of blood samples on study.

Who Is Running the Clinical Trial?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Rising Tide Foundation

Collaborator

Trials

17

Recruited

6,200+

Published Research Related to This Trial

A six-week exercise intervention combining high-intensity interval endurance and strength training significantly improved endurance (12% increase in VO2 peak) and strength (26% increase in cumulative load) in 15 breast cancer patients, while no adverse events were reported.

The intervention also enhanced the quality of life for participants, suggesting that this type of exercise can be safely integrated into the treatment plan for breast cancer patients, especially during medical treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility and effects of a combined adjuvant high-intensity interval/strength training in breast cancer patients: a single-center pilot study. Schulz, SVW., Laszlo, R., Otto, S., et al.[2018]

The Adapted Physical Activity and Diet (APAD) intervention, involving exercise and dietary counseling, significantly reduced fatigue and improved quality of life in 143 women with early breast cancer during chemotherapy and radiotherapy, with benefits lasting up to 12 months post-intervention.

Participants in the APAD group also experienced decreases in body mass index and fat mass, along with improvements in muscle endurance and cognitive flexibility, highlighting the multifaceted benefits of integrating diet and exercise into cancer treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short- and long-term impact of adapted physical activity and diet counseling during adjuvant breast cancer therapy: the "APAD1" randomized controlled trial. Carayol, M., Ninot, G., Senesse, P., et al.[2020]

Breast cancer patients, especially those with HER2+ tumors, face treatment-induced cardiotoxicity from standard therapies, making physical activity crucial for heart health during treatment.

Aerobic exercise may help protect against this cardiotoxicity, but there is a lack of standardized guidelines for exercise programs tailored to cancer patients, highlighting the need for further research to develop effective recommendations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment-Induced Cardiotoxicity in Breast Cancer: A Review of the Interest of Practicing a Physical Activity. Ginzac, A., Passildas, J., Gadéa, E., et al.[2019]

In a study involving 240 women undergoing chemotherapy for breast cancer, 16 weeks of concurrent resistance and high-intensity interval training (RT-HIIT) significantly improved muscle strength and reduced pain sensitivity compared to usual care.

Both RT-HIIT and moderate-intensity aerobic plus high-intensity interval training (AT-HIIT) effectively prevented declines in cardiorespiratory fitness and limited increases in body mass, demonstrating that these exercise programs are safe and beneficial during chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Highly favorable physiological responses to concurrent resistance and high-intensity interval training during chemotherapy: the OptiTrain breast cancer trial. Mijwel, S., Backman, M., Bolam, KA., et al.[2019]

In a study of 301 breast cancer patients undergoing chemotherapy, overall adherence to supervised exercise sessions was 73%, with significant predictors including location, fewer endocrine symptoms, and the type of exercise prescribed.

Patients with earlier stages of cancer (I/IIa) adhered well to all exercise types, while those with more advanced stages (IIb/III) showed better adherence to a standard dose of aerobic exercise, indicating that exercise prescription should be tailored based on disease stage and individual characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of adherence to different types and doses of supervised exercise during breast cancer chemotherapy. Courneya, KS., Segal, RJ., Gelmon, K., et al.[2021]

The CARE Trial, involving 301 breast cancer patients undergoing chemotherapy, found that a combined exercise program of aerobic and resistance training led to better long-term patient-reported outcomes, such as improved sleep quality and overall quality of life, compared to standard aerobic exercise alone.

Participants who engaged in the combined exercise regimen also showed superior health-related fitness, particularly in upper body muscular endurance, highlighting the benefits of incorporating resistance training during chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of exercise dose and type during breast cancer chemotherapy on longer-term patient-reported outcomes and health-related fitness: A randomized controlled trial. An, KY., Morielli, AR., Kang, DW., et al.[2020]

In a study involving 577 participants undergoing cancer treatment, exercise was found to be safe, with 20% of adverse events (AEs) reported by coaches and 28% by participants, mostly being minor musculoskeletal issues.

High-intensity exercise was associated with a higher likelihood of AEs compared to low-to-moderate exercise, but both forms of exercise are recommended for patients if there are no medical contraindications, as serious complications like lymphedema and PICC issues were low and not significantly different across exercise intensities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is it safe to exercise during oncological treatment? A study of adverse events during endurance and resistance training - data from the Phys-Can study. Henriksson, A., Johansson, B., Radu, C., et al.[2021]

In a pilot trial involving 10 breast cancer patients undergoing neoadjuvant chemotherapy, adding a supervised exercise program resulted in a significant decrease in body mass index (BMI) compared to those receiving chemotherapy alone (28.0 vs. 35.8, P = 0.03).

While the exercise group showed a trend towards lower Ki-67 levels (7% vs. 29%, P = 0.14), indicating potential benefits in tumor proliferation rates, the difference was not statistically significant, suggesting further research is needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bootcamp during neoadjuvant chemotherapy for breast cancer: a randomized pilot trial. Rao, R., Cruz, V., Peng, Y., et al.[2021]

High-intensity interval training (HIIT) has been shown to significantly improve cardiorespiratory fitness in breast cancer survivors, based on a review of 13 randomized controlled trials.

All HIIT interventions were supervised and lab-based, indicating a need for further research into the feasibility and effectiveness of home-based or unsupervised HIIT programs for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-intensity interval training in breast cancer survivors: a systematic review. Tsuji, K., Matsuoka, YJ., Ochi, E.[2021]

Exercise, including low-intensity activities like walking and Tai Chi, significantly reduces fatigue and improves overall quality of life for cancer patients during treatment, as shown in a systematic review of existing research.

While exercise benefits are well-documented, most studies focus on women with early-stage breast cancer, suggesting that more research is needed to understand its effects on other cancer populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise and cancer recovery. Visovsky, C., Dvorak, C.[2018]

In a pilot study involving breast cancer survivors, a 12-week home-based aerobic exercise program significantly reduced fatigue levels, indicating its effectiveness in managing cancer-related fatigue.

The resistance exercise program improved functional capacity, as shown by a significant increase in the distance walked during a 6-minute test, suggesting it is a viable strategy for enhancing physical function in breast cancer survivors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Home-based exercise to alleviate fatigue and improve functional capacity among breast cancer survivors. Yuen, HK., Sword, D.[2022]

In a study of 88 women undergoing chemotherapy, those who participated in high-intensity exercise programs showed lower levels of the biomarker Nt-pro-BNP one year after treatment compared to those who received usual care, suggesting a potential cardioprotective effect of exercise.

While plasma troponin-T levels increased in all groups immediately after treatment, fewer patients in the resistance and high-intensity interval training group met biomarker risk criteria at follow-up, indicating that high-intensity exercise may help mitigate cardiac risks associated with chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High intensity exercise during breast cancer chemotherapy - effects on long-term myocardial damage and physical capacity - data from the OptiTrain RCT. Ansund, J., Mijwel, S., Bolam, KA., et al.[2021]

A 3-week moderate intensity aerobic training program significantly improved aerobic capacity (VO2max) in 18 female breast cancer survivors, with increases of 11.86% in one group and 17.72% in another group.

The study demonstrated that both a predefined workload based on VO2max and a subjective exertion level led to similar improvements in aerobic capacity, indicating flexibility in training approaches for breast cancer survivors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of a short-term differently dosed aerobic exercise on maximum aerobic capacity in breast cancer survivors: a pilot study. Brdareski, Z., Djurović, A., Susnjar, S., et al.[2022]

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