Grape Seed Extract for Early Stage Lung Cancer

No longer recruiting at 1 trial location

Overseen By Jenny T Mao, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: VA Office of Research and Development

Must not be taking: CYP3A4 modulators, Investigational agents

Disqualifiers: Cognitive impairment, Respiratory disease, Angina, 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: 4

Duration: 2-3 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a treatment using grape seed extract, specifically leucoselect phytosome, for individuals with early-stage lung cancer. Researchers aim to determine if this extract can aid in treating lung cancer before surgery, potentially improving cure rates and reducing recurrence. Suitable candidates for this trial include those diagnosed with early-stage lung cancer that can be surgically removed and who have no severe other health issues. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you stop taking medications that affect cytochrome P450 3A4 unless an alternative can be provided. If you are on such medications, you may need to switch to a different one.

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

Research has shown that Leucoselect Phytosome, a special type of grape seed extract, was safe in earlier studies. Participants did not report any serious side effects, and it was generally well-tolerated for short periods.

Grape seed extracts, such as Leucoselect Phytosome, have been studied for their potential to fight cancer. They seem to slow the growth of cancer cells without harming healthy cells. Overall, participants in earlier studies experienced positive outcomes with few negative effects.

This extract is currently being tested specifically for lung cancer. Its current stage of testing indicates it has been deemed safe enough for broader trials. However, researchers will continue to monitor for any side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for early-stage lung cancer, which often include surgery, radiation, and chemotherapy, Leucoselect Phytosome offers a unique approach by using grape seed extract. Researchers are excited about this treatment because it takes advantage of the natural antioxidant properties of grape seed extract, which may help in fighting cancer cells with potentially fewer side effects. This could offer a gentler alternative to traditional therapies, making it particularly appealing for patients looking for less aggressive treatment options. Additionally, its oral administration makes it user-friendly and potentially easier to incorporate into daily life.

What evidence suggests that Leucoselect Phytosome might be an effective treatment for early stage lung cancer?

Research has shown that Leucoselect Phytosome, a special form of grape seed extract, can reduce signs of cancer in lung cells. Studies on mice found that grape seed extract slows lung cancer cell growth by blocking signals that promote cell growth. Early research suggests this extract might help prevent lung cancer. These promising results offer hope that Leucoselect Phytosome, which participants in this trial will receive, could effectively treat early-stage lung cancer in humans, possibly slowing cancer cell growth before surgery. ^{1 2 4 5 6}

Who Is on the Research Team?

Jenny T Mao, MD

Principal Investigator

VA San Diego Healthcare System, San Diego, CA

Are You a Good Fit for This Trial?

This trial is for early stage lung cancer patients who can consent, have a good performance status (0-1), normal blood counts and liver function, and lesions likely to be lung cancer. They must not have advanced respiratory disease, be pregnant or breastfeeding, take certain drugs affecting the liver enzyme P450 3A4, or consume more than one glass of wine daily.

Inclusion Criteria

I have suspicious lung lesions.

I am fully active or can carry out light work.

Your complete blood count (CBC) is normal.

Exclusion Criteria

You are currently breastfeeding.

I am taking medication that affects liver enzyme levels and cannot switch.

My lung function is strong enough for surgery.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive 2-3 weeks of oral LP treatment before surgical resection

2-3 weeks

Weekly phone follow-up

Surgery

Surgical resection of tumors with collection of post-treatment samples

Follow-up

Post-surgery follow-up to monitor safety and effectiveness

4 years

Phone follow-up at 3-4 weeks, 6 months, and annually

What Are the Treatments Tested in This Trial?

Interventions

• Leucoselect Phytosome

Trial Overview The study tests leucoselect phytosome (LP), a grape seed extract with enhanced absorption as pre-surgical treatment for early stage lung cancer. It's based on promising earlier results suggesting LP might improve outcomes and reduce recurrence in these patients.

How Is the Trial Designed?

Group I: Intervention Experimental Treatment 1 Intervention

All qualified participants meeting entry criteria that are enrolled will receive 2-3 weeks of oral LP treatment.

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Published Research Related to This Trial

Grape seed procyanidin extract (GSE) has shown potential as an anti-cancer agent by inhibiting pathways related to inflammation and cell proliferation in lung cancer cells, specifically through the modulation of prostacyclin (PGI2) and 15-hydroxyeicosatetraenoic acid (15-HETE).

In a lung cancer chemoprevention trial, GSE not only increased the production of PGI2 and 15-HETE but also demonstrated significant antiproliferative effects on lung premalignant and malignant cells, suggesting its efficacy as a chemopreventive agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Grape Seed Procyanidin Extract Mediates Antineoplastic Effects against Lung Cancer via Modulations of Prostacyclin and 15-HETE Eicosanoid Pathways. Mao, JT., Smoake, J., Park, HK., et al.[2021]

The combination of grape seed procyanidin extract (GSE) and milk thistle silymarin extract (MTE) significantly inhibited the growth of lung cancer cells in both cell lines and mouse models, demonstrating their potential as an effective treatment against lung cancer.

The study found that GSE and MTE were well-tolerated in mice without causing toxicity, and they worked together to enhance the expression of tumor suppressors miR-663a and FHIT, which are important for their anti-cancer effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combinations of grape seed procyanidin extract and milk thistle silymarin extract against lung cancer - The role of MiR-663a and FHIT. Mao, JT., Xue, B., Lu, QY., et al.[2023]

Grape seed extract (GSE) induces significant morphological changes in prostate cancer PC-3 cells, including cell shrinkage and membrane damage, indicating its potential effectiveness in cancer treatment.

The study demonstrated that GSE can lead to necrosis and apoptosis in PC-3 cells after 24, 48, and 72 hours of treatment, suggesting it may be a promising natural therapeutic agent against prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Grape seed extract induces morphological changes of prostate cancer PC-3 cells]. Shang, XJ., Yin, HL., Ge, JP., et al.[2009]

Liofenol™, a natural extract from red wine, significantly reduced the proliferation of colon cancer cells (HCT116) by activating key cell cycle regulators (p53 and p21) and increasing specific sphingolipid mediators, suggesting a potential mechanism for its anti-cancer effects.

The extract also enhanced the antioxidant response through the activation of the Nrf2 transcription factor, promoting differentiation of cancer cells without affecting their sensitivity to chemotherapy, indicating its potential as a supportive dietary intervention in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Natural grape extracts regulate colon cancer cells malignancy. Signorelli, P., Fabiani, C., Brizzolari, A., et al.[2015]

Grape seed extract (GSE) effectively inhibits the growth of prostate cancer PC-3 cells in a concentration- and time-dependent manner, suggesting its potential as a treatment for prostate cancer.

In contrast, GSE showed only a mild inhibitory effect on normal kidney cells, indicating a degree of safety for normal tissues while targeting cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Grape seed extract inhibits the growth of prostate cancer PC-3 cells]. Huang, TT., Shang, XJ., Yao, GH., et al.[2008]

A clinical study involving heavy active and former smokers showed that leucoselect phytosome, a grape seed procyanidin extract, significantly reduced bronchial cell proliferation, indicating its potential as a chemopreventive agent against lung cancer.

Treatment with leucoselect phytosome also improved serum levels of beneficial omega-3 fatty acids and their metabolites, which correlated with reduced cell proliferation in lung cancer cell lines, suggesting both cardiovascular and anti-cancer benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Leucoselect Phytosome Modulates Serum Eicosapentaenoic Acid, Docosahexaenoic Acid, and Prostaglandin E3 in a Phase I Lung Cancer Chemoprevention Study. Mao, JT., Xue, B., Fan, S., et al.[2022]

A clinical study involving 8 participants (ages 46-68) found that leucoselect phytosome (LP), a grape seed procyanidin extract, was well tolerated over 3 months, with no dose adjustments needed, indicating its safety for use in heavy smokers.

Treatment with LP resulted in a significant 55% reduction in bronchial Ki-67 labeling index, a marker of cell proliferation, suggesting its potential effectiveness as a chemopreventive agent against lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Pilot Study of a Grape Seed Procyanidin Extract for Lung Cancer Chemoprevention. Mao, JT., Lu, QY., Xue, B., et al.[2023]

High concentrations of grape seed extract (GSE) (50-400 μg/ml) significantly inhibited the growth of oral cancer cells (Ca9-22) and induced apoptosis, while low concentrations (1-10 μg/ml) had only a mild effect.

The study found that higher GSE concentrations increased reactive oxygen species (ROS) production and mitochondrial dysfunction, leading to greater DNA damage in cancer cells, suggesting that GSE's antiproliferative effects are concentration-dependent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concentration effects of grape seed extracts in anti-oral cancer cells involving differential apoptosis, oxidative stress, and DNA damage. Yen, CY., Hou, MF., Yang, ZW., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8225569/

LEUCOSELECT PHYTOSOME MODULATES SERUM ... Grape seed procyanidin extract (GSE) has been shown to exert antineoplastic properties in preclinical studies. Recently we reported findings from a modified ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04515004

Study Details | NCT04515004 | Leucoselect Phytosome for ... The investigators will conduct a phase IIa, single arm study using 2-3 weeks of oral LP treatment for 30 early stage I and II lung cancer patients before ...

3. withpower.com withpower.com/trial/phase-3-lung-neoplasms-10-2021-3082e

Grape Seed Extract for Early Stage Lung Cancer Research shows that Leucoselect Phytosome, a grape seed extract combined with soy phospholipids, can reduce cell growth markers in the lungs and increase ...

4. aacrjournals.org aacrjournals.org/cancerpreventionresearch/article/9/12/925/50505/Grape-Seed-Procyanidin-Extract-Mediates

Grape Seed Procyanidin Extract Mediates Antineoplastic ... Recently, preclinical studies have shown that GSE inhibited human non–small cell lung cancer (NSCLC) xenografts growth in mice, in part, through the inhibition ...

5. reporter.nih.gov reporter.nih.gov/search/V7Psp3mky0KB-sMpn0B2PQ/project-details/10729099

Leucoselect Phytosome for Neoadjuvant Treatment of Early Stage ... Ample preclinical data suggests that grape seed procyanidin extract (GSE) possesses multi-faceted anticancer properties. GSE has been shown to favorably ...

6. reporter.nih.gov reporter.nih.gov/search/t_kbDTVMR0KOnhtdmsXJ0w/project-details/10729099

Leucoselect Phytosome for Neoadjuvant Treatment of Early ... Ample preclinical data suggests that grape seed procyanidin extract (GSE) possesses multi-faceted anticancer properties. GSE has been shown to favorably ...