Phase 1b of Lurbinectedin in Combination With Weekly Paclitaxel and Bevacizumab in Platinum-resistant Ovarian Cancer
To learn if adding lurbinectedin to the combination of paclitaxel and bevacizumab can help to control advanced cancer.
• Ability to provide signed informed consent in accordance with federal, local, and institutional guidelines.
• Age ≥ 18 years at time of study entry
• Willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
• Histologically confirmed and documented ovarian, fallopian tube or peritoneal carcinoma: Patients with platinum refractory\* or platinum resistant\*\* disease are allowed. Prior anti-VEGF targeted therapy (e.g. bevacizumab, VEGF TKI's) is allowed.
‣ Platinum refractory is defined as progression during platinum-containing therapy or within 4 weeks of last dose.
⁃ Platinum resistant is defined as relapse-free interval 1-6 months of a platinum-containing therapy
• Prior Therapy: Unlimited prior systemic therapies are allowed.
• ECOG performance status of 0-1 (Appendix A)
• Adequate normal organ and marrow function as defined below.
∙ Hemoglobin ≥9.0 g/dL.
‣ Absolute neutrophil count (ANC) \> 1500/mm3.
‣ Platelet count ≥100 x 109/L
‣ Serum bilirubin ≤1.5 x ULN. This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.
‣ AST (SGOT)/ALT (SGPT) ≤2.5 x ULN unless liver metastases are present, in which case it must be ≤5x ULN.
‣ Measured creatinine clearance (CL) \>40 mL/min or Calculated creatinine CL\>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:
• Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 72 x serum creatinine (mg/dL)
• Evidence of post-menopausal status or negative urine or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
∙ Women \<50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
‣ Female patients of child-bearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test at screening, and male patients must use an effective barrier method of contraception if sexually active with a female of child-bearing potential. Acceptable methods of contraception are condoms with contraceptive foam, oral, implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is surgically sterilized or post-menopausal. For both male and female patients, effective methods of contraception must be used throughout the study and for three months following the last dose.
‣ Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \>1 year ago, had chemotherapy-induced menopause with last menses \>1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy).
• Measurable disease by RECIST v1.1