Ashwagandha + DOXIL for Ovarian Cancer

Overseen By Whitney Goldsberry, MD

Age: 18+

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: Sham Sunder Kakar

Must be taking: Liposomal doxorubicin

Must not be taking: Other anticancer drugs

Disqualifiers: Brain metastases, Active infection, Heart failure, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 14

72 Participants Needed

Trial Summary

What is the purpose of this trial?

The proposed study "combination therapy with liposomal doxorubicin and withaferin A (Ashwagandha, ASWD) in recurrent ovarian cancer" is focused to determine the feasibility and maximum tolerance dose of Ashwagandha with liposomal doxorubicin (DOXIL) in recurrent ovarian cancer patients. The study contains two parts. In part 1 (phase I), 18 patients with recurrent ovarian cancer eligible for DOXIL therapy will be recruited and three doses of Ashwagandha (2.0 g, 4.0 g and 8.0 g) in the form of tablets along with DOXIL will be evaluated for feasibility and tolerance of ASWD. In part 2 (phase II), 54 patients with recurrent ovarian cancer will be recruited and treated with DOXIL and Ashwagandha (dose determined from part 1) to evaluate the complete response (CR), partial response (PR), and stable disease (SD).

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it does require that you discontinue all prior cancer therapies at least 4 weeks before starting the study treatment.

What data supports the effectiveness of the drug Ashwagandha + DOXIL for ovarian cancer?

Research shows that DOXIL, a form of doxorubicin, is effective in treating recurrent ovarian cancer and has a unique ability to target tumor sites due to its formulation. While Ashwagandha's specific role in this combination isn't detailed, DOXIL's established effectiveness in ovarian cancer provides a basis for its use in this trial. ^{1 2 3 4 5}

Is the combination of Ashwagandha and DOXIL safe for treating ovarian cancer?

DOXIL, a form of the chemotherapy drug doxorubicin, has been shown to have a different safety profile compared to traditional doxorubicin, with less heart-related side effects and more skin and mouth-related side effects. It is approved for use in recurrent ovarian cancer and has been studied for safety in various cancers. However, specific safety data for the combination of Ashwagandha and DOXIL is not available. ^{1 2 3 4 6}

What makes the drug Ashwagandha + DOXIL unique for treating ovarian cancer?

The drug Ashwagandha + DOXIL is unique for treating ovarian cancer because DOXIL is a pegylated liposomal formulation of doxorubicin, which allows it to circulate longer in the bloodstream and target tumor sites more effectively, reducing toxicity compared to traditional doxorubicin. This formulation is specifically designed to enhance therapeutic efficacy and minimize side effects, making it a novel approach in ovarian cancer treatment. ^{1 2 3 7 8}

Research Team

Whitney Goldsberry, MD

Principal Investigator

Brown Cancer Center at University of Louisville

Eligibility Criteria

This trial is for women over 18 with recurrent ovarian cancer, including various subtypes, who've had at least two prior chemotherapy treatments (one platinum-based) and haven't been treated with liposomal doxorubicin. They should understand the study's experimental nature, have a life expectancy over six months, and measurable disease or elevated CA 125 levels.

Inclusion Criteria

My cancer has come back, confirmed by tests or high CA 125 levels.

My cancer can be measured or seen on tests.

I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

I am mostly bedridden due to my health condition.

I have a serious heart lining condition.

I have been treated with liposomal doxorubicin before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase I

Feasibility and tolerability evaluation with dose escalation of Ashwagandha in combination with DOXIL

16 weeks

4 visits (in-person, every 4 weeks)

Treatment Phase II

Evaluation of overall survival and response rate with maximum tolerable dose of Ashwagandha and DOXIL

Up to 2 years

10 visits (in-person, every 4 weeks)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 years

Treatment Details

Interventions

• Ashwagandha
• DOXIL
• Withaferin A

Trial Overview The study tests combining Ashwagandha (ASWD) in tablet form at different doses (2g, 4g, 8g) with DOXIL to find the safest high dose of ASWD. It will then assess how well this combination works to improve outcomes like complete response or stable disease in patients.

Participant Groups

Group I: Combination of DOXIL and Ashwagandha Experimental Treatment 4 Interventions

The study contains two parts. In part 1 (Phase I), 18 patients with recurrent ovarian cancer will be recruited and administered IV with liposomal doxorubicin (DOXIL) 40 mg/m2 on day 1 of 28 days cycle for 4 cycles. Ashwagandha will be administered on daily basis for 2 years. Three doses of Ashwagandha (2 g, 4 g or 8.0 g) will be administered orally with water every day for two years to evaluate a tolerable dose of Ashwagandha. Six patients will be recruited for each dose. In part 2 Phase II), 54 additional patients with recurrent ovarian cancer will be recruited and administered with DOXIL IV (40 mg/m2) and maximum tolerable dose of Ashwagandha (determined from part 1) in the form tables orally with water on daily basis for two years. The survival rate (SR), complete response (CR) and partial response (PR) will be evaluated.

DOXIL is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Doxil for:

• Ovarian cancer
• AIDS-related Kaposi's sarcoma
• Multiple myeloma

Approved in European Union as Caelyx for:

• Ovarian cancer
• AIDS-related Kaposi's sarcoma
• Multiple myeloma
• Breast cancer

Approved in Canada as Liposomal Doxorubicin for:

• Ovarian cancer
• AIDS-related Kaposi's sarcoma
• Multiple myeloma

Approved in Japan as Doxorubicin Hydrochloride Liposome Injection for:

• Ovarian cancer
• AIDS-related Kaposi's sarcoma

Who Is Running the Clinical Trial?

Sham Sunder Kakar

Lead Sponsor

Trials

1

Recruited

70+

University of Louisville Health Care

Collaborator

Trials

1

Recruited

70+

Findings from Research

Caelyx/Doxil, a pegylated liposomal formulation of doxorubicin, has a unique pharmacokinetic profile that allows it to effectively target tumor sites while reducing toxicity compared to traditional doxorubicin.

It has been approved by the FDA and EMEA for treating AIDS-related Kaposi's sarcoma and recurrent epithelial ovarian cancer, and is being investigated for use in various other cancers, indicating its potential as a versatile treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Caelyx/Doxil for the treatment of metastatic ovarian and breast cancer. Tejada-Berges, T., Granai, CO., Gordinier, M., et al.[2022]

Pegylated liposomal doxorubicin (Doxil) has a unique toxicity profile compared to conventional doxorubicin, showing less cardiac toxicity and minimal hair loss, while primarily causing mucocutaneous toxicities and mild myelosuppression.

Doxil is particularly effective in treating AIDS-related Kaposi's sarcoma and recurrent ovarian cancer, with ongoing research exploring its potential in other cancers and in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegylated liposomal doxorubicin: metamorphosis of an old drug into a new form of chemotherapy. Gabizon, AA.[2022]

In a phase II study involving 63 patients with ovarian cancer, pegylated liposomal doxorubicin (Doxil) showed a response rate of 19% in patients with measurable disease and a median overall survival of 10 months, indicating its efficacy in a heavily pretreated population.

Doxil was well tolerated, with manageable side effects; serious toxicities were relatively low, and nausea and vomiting were uncommon, suggesting a favorable safety profile compared to traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of liposomal doxorubicin in advanced gynecologic cancers. Israel, VP., Garcia, AA., Roman, L., et al.[2013]

The study found that the generic doxorubicin liposome injection developed by Sun Pharmaceuticals (SPIL) has a plasma and tissue distribution profile that is generally comparable to the reference product, Caelyx®, in murine models.

Minor differences in tissue distribution were noted, but these variations were likely due to biological differences rather than significant discrepancies between the two formulations, suggesting that SPIL's product may offer a similar benefit-risk profile as Caelyx®.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative plasma and tissue distribution of Sun Pharma's generic doxorubicin HCl liposome injection versus Caelyx® (doxorubicin HCl liposome injection) in syngeneic fibrosarcoma-bearing BALB/c mice and Sprague-Dawley rats. Burade, V., Bhowmick, S., Maiti, K., et al.[2018]

A modified regimen of liposomal doxorubicin at 40 mg/m² every 4 weeks resulted in significantly less toxicity compared to the standard dose, with only 12% of patients experiencing grade 2 hand-foot syndrome and 8% experiencing stomatitis.

Despite the reduced toxicity, the treatment showed limited antineoplastic activity, with 9% of evaluable patients demonstrating an objective response in a group of 49 patients with platinum/paclitaxel-refractory ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 trial of liposomal doxorubicin (40 mg/m(2)) in platinum/paclitaxel-refractory ovarian and fallopian tube cancers and primary carcinoma of the peritoneum. Markman, M., Kennedy, A., Webster, K., et al.[2022]

In a study of 42 patients receiving cumulative doses of pegylated liposomal doxorubicin (doxil) exceeding 500 mg/m2, none developed clinical congestive heart failure, indicating a favorable safety profile for higher doses compared to traditional doxorubicin.

While five patients experienced a drop in left ventricular ejection fraction (LVEF), the overall risk of cardiomyopathy appears significantly lower with doxil, even in patients previously treated with doxorubicin, suggesting that doxil may be a safer option for patients with solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegylated liposomal doxorubicin (doxil): reduced clinical cardiotoxicity in patients reaching or exceeding cumulative doses of 500 mg/m2. Safra, T., Muggia, F., Jeffers, S., et al.[2022]

Doxil-liposomal topotecan (Topophore C) combinations showed promising synergistic effects in treating ovarian cancer, particularly in the ES-2 and OVCAR-3 cell lines, indicating enhanced therapeutic potential compared to individual drugs.

In animal models, the combination of Topophore C and Doxil significantly increased median survival time to 52 days, compared to 18 days for untreated animals and 40 days for Topophore C alone, demonstrating the efficacy of this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topotecan and doxorubicin combination to treat recurrent ovarian cancer: the influence of drug exposure time and delivery systems to achieve optimum therapeutic activity. Patankar, NA., Pritchard, J., van Grinsven, M., et al.[2018]

The study developed a nano-liposomal formulation that effectively co-delivers cisplatin and doxorubicin, achieving high entrapment efficiencies of 85.29% and 73.62%, respectively, which helps to overcome chemotherapy resistance in ovarian cancer.

Cisplatin and doxorubicin-loaded liposomes demonstrated enhanced cytotoxicity against ovarian cancer cells (A2780) compared to free drug combinations, while also showing improved biocompatibility with normal cells, indicating a promising strategy for reducing toxicity and improving treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preparation, characterization, and Co-delivery of cisplatin and doxorubicin-loaded liposomes to enhance anticancer Activities. Bahrami Parsa, M., Tafvizi, F., Chaleshi, V., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Caelyx/Doxil for the treatment of metastatic ovarian and breast cancer. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Pegylated liposomal doxorubicin: metamorphosis of an old drug into a new form of chemotherapy. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Phase II study of liposomal doxorubicin in advanced gynecologic cancers. [2013]

4. Germany pubmed.ncbi.nlm.nih.gov

Comparative plasma and tissue distribution of Sun Pharma's generic doxorubicin HCl liposome injection versus Caelyx® (doxorubicin HCl liposome injection) in syngeneic fibrosarcoma-bearing BALB/c mice and Sprague-Dawley rats. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Phase 2 trial of liposomal doxorubicin (40 mg/m(2)) in platinum/paclitaxel-refractory ovarian and fallopian tube cancers and primary carcinoma of the peritoneum. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Pegylated liposomal doxorubicin (doxil): reduced clinical cardiotoxicity in patients reaching or exceeding cumulative doses of 500 mg/m2. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Topotecan and doxorubicin combination to treat recurrent ovarian cancer: the influence of drug exposure time and delivery systems to achieve optimum therapeutic activity. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Preparation, characterization, and Co-delivery of cisplatin and doxorubicin-loaded liposomes to enhance anticancer Activities. [2023]