Combination Therapy for Recurrent Ovarian Cancer

NCT05610735 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 22.0392
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Recurrent Ovarian Cancer

Keywords

DOXIL; Withaferin A; Ashwagandha; Recurrent Ovarian Cancer; Combination therapy

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  Will be presented by Kaplan Meier methods.

  From study entry to time of progression or death, whichever occurs first, assessed up to 4 years.

Secondary Outcomes (4)

• Incidence of adverse events (AE)

  From study entry, up to 4 years.

• Objective response rate (ORR)

  From the start of the treatment until disease progression/recurrence, assessed up to 4 years

• Duration of response

  From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 4 years.

• Overall survival

  Time from study entry to date of death from any cause, assessed up to 4 years

Study Arms (1)

Combination of DOXIL and Ashwagandha

EXPERIMENTAL

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.

Drug: DOXIL; Drug: Withaferin A; Drug: Ashwagandha; Drug: Combination of ASWD and DOXIL

Interventions

Withaferin A DRUG

Ashwagandha in the form of tablets will be administered orally on daily basis.

Also known as: Ashwagandha

Combination of DOXIL and Ashwagandha

Ashwagandha DRUG

Administered orally on daily basis twice a day

Also known as: ASWD

Combination of DOXIL and Ashwagandha

DOXIL DRUG

DOXIL will be administered IV as 40 mg/m2 IV every four weeks for 4 cycles or until disease progression and/or unacceptable toxicity, whichever comes first to a maximum of 10 cycles.

Also known as: Liposomal doxorubicin

Combination of DOXIL and Ashwagandha

Combination of ASWD and DOXIL DRUG

DOXIL administered IV once every four weeks. ASWD administered orally on daily basis, twice a day.

Also known as: ASWD and DOXIL

Combination of DOXIL and Ashwagandha

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Pathological confirmed ovarian, fallopian tube, or primary peritoneal carcinoma with the one of the following histologic types: high grade papillary serous carcinoma, low grade papillary serous carcinoma, high grade mucinous carcinoma, low grade mucinous carcinoma, clear cell carcinoma, high grade endometrioid carcinoma, undifferentiated carcinoma, mixed epithelial carcinoma, and adenocarcinomas not otherwise specified
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with recurrent ovarian/fallopian tube/primary peritoneal cancer for whom liposomal Doxorubicin would be an acceptable therapeutic option will be recruited. Patients are eligible if they have received first line chemotherapy containing platinum and have become platinum resistance or have refractory disease. The patient must also meet all the following criteria:
• Signed approved informed consent document stating that they understand the investigational nature of the treatment program before entering study
• Female patients, age ≥ 18 years
• Pathological confirmed ovarian, fallopian tube, or primary peritoneal carcinoma with the one of the following histologic types: high grade papillary serous carcinoma, low grade papillary serous carcinoma, high grade mucinous carcinoma, low grade mucinous carcinoma, clear cell carcinoma, high grade endometrioid carcinoma.
• Received at least one line chemotherapy, which must be a platinum containing regimen and develop platinum resistance. Patients may have not received previous liposomal doxorubicin therapy, and must be considered to be eligible for single agent liposomal doxorubicin treatment.
• Patients may have undergone surgical cytoreduction at the time of primary diagnosis or following neoadjuvant chemotherapy. Patients who had optimal (\<1 cm residual disease) or suboptimal (\>1 cm residual disease) following surgical cytoreduction will be included.
• Patients who did not undergo surgical cytoreduction will also be included.
• Recurrent disease confirmed by biopsy, radiologic imaging, and/or elevated CA 125
• Patients may have received radiation therapy
• Life expectancy \> 6 months
• Part 1: Have evaluable disease by radiologic measurements (See 11) or CA 125
• Part 2: Have measurable disease, defined as at least 1 lesion that can be accurately measured in at least 1 dimension (longest diameter to be recorded) as \> 1 cm on cross-sectional imaging (where the CT slice thickness is no greater than 5 mm) or at least 2 cm by standard techniques; positron emissions tomography (PET\] and ultrasound are not permitted methods for tumor measurements under this protocol. Consult RECIST 1.1 guidance for additional information (Appendix C and Eisenhauer et al., 2009; Ref 61).
• Adequate organ function within 14 days prior to first WFA/ASWD dose or liposomal doxorubicin whichever occurs first, including the following: absolute neutrophil count (ANC) ≥ 1.5 x 103/L, platelet count ≥ 100 x 103/L, hemoglobin ≥ 9 g/dL (≥ 5.6 mmol/L), patients may receive packed RBC transfusion to achieve this level at the discretion of the investigator, total bilirubin \< 1.5 x upper limit of normal (ULN) unless elevated secondary to conditions such as Gilbert's Disease, aspartate aminotransferase (AST) \< 3 x ULN (\< 5 x ULN in the presence of hepatic metastases), alanine aminotransferase (ALT) \< 3 x ULN (\< 5 x ULN in the presence of hepatic metastases), alkaline phosphatase \< 3.0 x ULN, calculated creatinine clearance ≥ 60 mL/min per Cockcroft and Gault formula
• Satisfy one of the following:
• Females: non-pregnant and non-lactating; surgically sterile, post- menopausal, or patient/partner compliant with a reliable contraceptive regimen, as determined by the investigator, for 4 weeks prior to screening.

You may not qualify if:

• Patients will be excluded from the study if they meet any of the following criteria:
• ECOG performance status 3 or 4
• Pregnant or breastfeeding
• Treatment with another investigational drug, biological agent, or device within 4 weeks (6 weeks for biological agents) before screening or 5 half-lives of study agent, whichever is longer
• Patients with treated or untreated parenchymal brain metastases or leptomeningeal disease. Brain imaging is required for symptomatic patients to rule out brain metastases, but is not required in asymptomatic patients
• Patients with known pericardial effusion
• Patients with active infection or serious concomitant systemic disorder (for example, heart failure) incompatible with the study (at the discretion of the Investigator)
• Presence or history of malignancy other than ovarian cancer that does not include carcinoma in situ of the cervix, or non-melanoma skin cancer. In the case of other malignancies, patients may be considered for participation if the prior malignancies were diagnosed and definitively treated at least two years previously with no subsequent evidence of recurrence
• Presence of an underlying disease state associated with active bleeding
• Concurrent treatment with other anticancer drugs
• Planned concomitant participation in another clinical trial of an experimental agent, vaccine, or device
• Patients with any other medical conditions that, in the opinion of the Investigator, would make the patient unsuitable for enrollment, or could interfere with the patient participating in or completing the study
• Patients with known septicemia, severe infection, or acute hepatitis
• Patients with known congestive heart failure or unstable angina or those who had a myocardial infarction within the past 6 months
• Patients with known clinically significant pericardial disease

Sponsors & Collaborators

• Sham Sunder Kakar: lead
• University of Louisville: collaborator

Study Sites (1)

UofL Health Brown Cancer Center

Louisville, Kentucky, 40202, United States

RECRUITING

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

liposomal doxorubicin; withaferin A; Ashwagandha

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Study Officials

• Whitney Goldsberry, MD

  Brown Cancer Center at University of Louisville

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sham Kakar, PhD

CONTACT

(502) 931-1485; sham.kakar@louisville.edu

Whitney Goldsberry, MD

CONTACT

502-562-4370; Whitney.Goldsberry@uoflhealth.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: Recurrent Ovarian Cancer Participants treated with combination of DOXIL and Ashwagandha

Study Record Dates

• First Submitted: September 26, 2022
• First Posted: November 9, 2022
• Study Start: September 25, 2024
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): November 30, 2028
• Last Updated: March 19, 2026

Record last verified: 2026-03

Locations

US (1)