TAME: A Pilot Study of Weekly Paclitaxel, Bevacizumab, and Tumor Associated Macrophage Targeted Therapy (Zoledronic Acid) in Women With Recurrent, Platinum-resistant, Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer

Participants are excluded from the study if any of the following criteria apply within 28 days of starting study treatment.

1. Nonepithelial tumors including carcinosarcomas. Mucinous ovarian cancers. Ovarian tumors with low malignant potential or low-grade epithelial tumors.

2. Patients who have received anti-VEGF targeted therapy (alone or in combination with chemotherapy or other biological agents) for recurrent disease and have progressed on that therapy or within 6 months of discontinuation of that therapy. Prior bevacizumab in the upfront setting is permitted.

3. History of other clinically active malignancy within 5 years of enrollment, except for tumors with a negligible risk for metastasis or death, such as adequately controlled basal-cell carcinoma or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix or breast, or early stage endometrial cancer (stage IA/B, Grade 1 or 2, endometrioid histology).

4. Patients with known or suspected conditions likely to increase gastrointestinal toxicity, such as, inflammatory bowel disease, bowel obstruction, history of bowel obstruction or overt bowel involvement by tumor.

5. History of bowel obstruction, including sub-occlusive disease, related to the underlying disease and history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess. Evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction.

6. Patients who are pregnant or lactating.

7. Radiation, chemotherapy, or immunotherapy or any other anticancer therapy ≤2 weeks prior to cycle 1 day 1.

8. Major surgery (including open biopsy, surgical resection, wound revision, or any other major surgery involving entry into a body cavity) or significant traumatic injury within four weeks before Day 1.

9. Unstable cardiovascular function:

* ECG abnormalities requiring treatment, or

* congestive heart failure (CHF) of NYHA Class ≥3, or

* myocardial infarction (MI) within 3 months.

10. Uncontrolled infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose; patients with controlled infection or on prophylactic antibiotics are permitted in the study.

11. Known active hepatitis A, B, or C infection; or known to be positive for HCV RNA or HBsAg (HBV surface antigen); Known to be HIV seropositive

12. Any underlying condition that would significantly interfere with the absorption of an oral medication.

13. Grade \>2 peripheral neuropathy at baseline (within 14 days prior to cycle 1 day 1).

14. Patients with urine dipstick for proteinuria \>2+. Patients with ≥2+ proteinuria on baseline dipstick analysis should undergo a 24-hour urine collection and must demonstrate ≤1 g of protein in the 24-hour urine. Alternatively, proteinuria testing can be performed according to local standards.

15. Serious psychiatric or medical conditions that could interfere with treatment;

16. Participation in an investigational anti-cancer study within 3 weeks prior to Cycle 1 Day 1

17. Concurrent therapy with approved or investigational anticancer therapeutic other than steroids.

18. Patients with coagulation problems and active bleeding within 4 weeks prior to C1D1 (peptic ulcer, epistaxis, spontaneous bleeding)

19. Patients with symptomatic brain lesions

20. For women who are not postmenopausal (\<12 months of non therapy-induced amenorrhea, with no identified cause other than menopause) and have not undergone surgical sterilization (removal of ovaries and/or uterus): agreement to remain abstinent (refrain from heterosexual intercourse) or use two adequate non hormonal methods of contraception, including at least one method with a failure rate of \<1% per year, during the treatment period and for at least 4 months after the last dose of study drug

What this study is about