Phase 1b of Lurbinectedin in Combination With Weekly Paclitaxel and Bevacizumab in Platinum-resistant Ovarian Cancer

Trial Title: Phase 1b of Lurbinectedin in Combination With Weekly Paclitaxel and Bevacizumab in Platinum-resistant Ovarian Cancer

NCT ID: NCT05636111

Condition: Ovarian Cancer

Conditions: Official terms:
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Paclitaxel
Bevacizumab

Study type: Interventional

Study phase: Phase 1

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Paclitaxel
Description: Given by (IV) vein
Arm group label: Dose Escalation and Dose Expansion

Other name: Taxol

Intervention type: Drug
Intervention name: Bevacizumab
Description: Given by (IV) vein
Arm group label: Dose Escalation and Dose Expansion

Other name: Avastin™

Other name: Anti-VEGF monoclonal antibody

Other name: rhuMAb-VEGF

Intervention type: Drug
Intervention name: Lurbinectedin
Description: Given by (IV) vein
Arm group label: Dose Escalation and Dose Expansion

Summary: To learn if adding lurbinectedin to the combination of paclitaxel and bevacizumab can help to control advanced cancer.

Detailed description: Primary Objectives: - To identify dose-limiting toxicities (DLTs) and recommended phase 2 dose (RP2D) of the combination of paclitaxel/bevacizumab/lurbinectedin in women with platinum resistant ovarian cancer. - To assess macrophage counts by image cytometry in women with platinum resistant ovarian cancer treated with weekly paclitaxel/bevacizumab/lurbinectedin. Secondary Objectives: - To assess objective response (OR) and duration of response (DOR). - To assess clinical benefit rate (CBR), defined as proportion of patients with OR or stable disease (SD) > 4 months. - To estimate progression free survival (PFS) and overall survival (OS) for at least 12 months Exploratory Objectives: --To assess differential effects from baseline, within and between patient treatment cohorts, on macrophage and hypoxia markers, CSF1/R and MHCII, plasma biomarker (VEGF, VEGFR, IL6, IL8, FGF, PDGFAA), tumor and macrophage-derived exosomes, resident macrophage populations in tissue pre-enrollment and after induction bevacizumab (CD11b +CD68, CD11b +CD14/CD15/CD33, CD11b +CD11c, MHCII, CD168+, CD4/CD8, NK, Treg) by multicolor tissue cytometry, as well as serial changes in vivo imaging such as tumor size, macrophage-specific imaging, ADC for cellularity, and DCE for vasculature.

Criteria for eligibility:
Criteria:
Inclusion Criteria: Inclusion criteria will be assessed within 28 days of starting study treatment: 1. Ability to provide signed informed consent in accordance with federal, local, and institutional guidelines. 2. Age ≥ 18 years at time of study entry 3. 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. 4. Histologically confirmed and documented ovarian, fallopian tube or peritoneal carcinoma: both platinum refractory* and platinum resistant** patients. Anti-VEGF targeted therapy (e.g. bevacizumab, VEGF TKI's) is allowed as part of initial therapy and/or maintenance. No prior anti-VEGF in combination with chemotherapy for treatment of platinum-resistant/platinum-refractory disease. 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 5. Prior Therapy: Unlimited prior systemic therapies are allowed. 6. ECOG performance status of 0-1 (Appendix A) 7. Adequate normal organ and marrow function as defined below. 1. Hemoglobin ≥9.0 g/dL. 2. Absolute neutrophil count (ANC) > 1500/mm3. 3. Platelet count ≥100 x 109/L 4. 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. 5. AST (SGOT)/ALT (SGPT) ≤2.5 x ULN unless liver metastases are present, in which case it must be ≤5x ULN. 6. 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) 8. 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: 1. 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). 2. 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. 3. 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). Exclusion Criteria: Exclusion criteria will be assessed within 28 days of starting study treatment. Patients meeting any of the following exclusion criteria are not eligible to enroll in this study. 1. Patients who have received anti-VEGF targeted therapy (in combination with chemotherapy) for platinum-resistant/platinum-refractory recurrent disease. 2. Radiation, chemotherapy, or immunotherapy or any other anticancer therapy ≤2 weeks prior to cycle 1 day 1. 3. Use of an anti-cancer treatment drug or investigational drug during the last 28 days or 5 half-lives (whichever is shorter) prior to cycle 1 day 1. A minimum of 10 days between termination of prior treatment and administration of study treatment is required. 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. Patients who are pregnant or lactating. 6. Major surgery 2 peripheral neuropathy at baseline (within 14 days prior to cycle 1 day 1). 11. Serious psychiatric or medical conditions that could interfere with treatment; 12. Participation in an investigational anti-cancer study within 3 weeks prior to Cycle 1 Day 1 13. Concurrent therapy with approved or investigational anticancer therapeutic other than steroids. 14. Patients with coagulation problems and active bleeding within 4 weeks prior to C1D1 (peptic ulcer, epistaxis, spontaneous bleeding) 15. Patients with symptomatic brain lesions 16. Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation). 17. History of hemoptysis (1/2 teaspoon of bright red blood per episode) within 1 month of study enrollment for any tumor type. 18. Non-healing wound, ulcer or bone fracture. 19. Known hypersensitivity to lurbinectedin, paclitaxel, bevacizumab or excipients.

Gender: Female

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: M D Anderson Cancer Center

Address:
City: Houston
Zip: 77030
Country: United States

Status: Recruiting

Contact:
Last name: Shannon Westin, MD

Phone: 713-794-4314
Email: swestin@mdanderson.org

Investigator:
Last name: Shannon Westin, MD
Email: Principal Investigator

Start date: July 12, 2023

Completion date: July 31, 2026

Lead sponsor:
Agency: M.D. Anderson Cancer Center
Agency class: Other

Collaborator:
Agency: Jazz Pharmaceuticals
Agency class: Industry

Source: M.D. Anderson Cancer Center

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05636111
http://www.mdanderson.org