Combination therapy for recurrent ovarian cancer using doxorubicin and Ashwagandha

Inclusion Criteria:

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:

1. Signed approved informed consent document stating that they understand the investigational nature of the treatment program before entering study
2. Female patients, age ≥ 18 years
3. 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.
4. 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.
5. 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.
6. Recurrent disease confirmed by biopsy, radiologic imaging, and/or elevated CA 125
7. Patients may have received radiation therapy
8. Life expectancy \> 6 months
9. Part 1: Have evaluable disease by radiologic measurements (See 11) or CA 125
10. 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).
11. 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
12. 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.
    * Patients of reproductive potential must test negative for pregnancy at screening, prior to each cycle, and must agree to use a reliable method of birth control during the study period and 6 months following completion of treatment.
13. The patient is willing and able to comply with the study visit schedule and procedures and has geographical proximity (Investigator's discretion) that allows follow-up specified by the protocol
14. For Part 1: Patients have discontinued all prior chemotherapies, biological therapies, and other investigational therapies for cancer for at least 4 weeks prior to study treatment and have recovered from the acute effects of therapy
15. ECOG performance status of 0, 1, or 2
16. Adequate ejection fraction determined by transthoracic echo or MUGA of at least 55%
17. Patients may have received prior anthracycline or anthracenedione therapy. In this scenario, the use of prior treatments will be incorporated into the cumulative dose calculations when applicable, given a known increased risk of cardiomyopathy to 11% when the cumulative dose of liposomal doxorubicin was between 450 mg/m2 to 550 mg/m2.

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Exclusion Criteria:

Patients will be excluded from the study if they meet any of the following criteria:

1. ECOG performance status 3 or 4
2. Pregnant or breastfeeding
3. 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
4. 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
5. Patients with known pericardial effusion
6. Patients with active infection or serious concomitant systemic disorder (for example, heart failure) incompatible with the study (at the discretion of the Investigator)
7. 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
8. Presence of an underlying disease state associated with active bleeding
9. Concurrent treatment with other anticancer drugs
10. Planned concomitant participation in another clinical trial of an experimental agent, vaccine, or device
11. 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
12. Patients with known septicemia, severe infection, or acute hepatitis
13. Patients with known congestive heart failure or unstable angina or those who had a myocardial infarction within the past 6 months
14. Patients with known clinically significant pericardial disease
15. Patients taking medications known to affect the cardiac conduction system
16. Allergy to WFA/ASWD
17. Previous treatment with liposomal doxorubicin
18. Prior use of other anthracyclines or anthracenediones -