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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT05636111
Recruitment Status : Not yet recruiting
First Posted : December 5, 2022
Last Update Posted : June 5, 2023
Jazz Pharmaceuticals
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

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

Condition or disease Intervention/treatment Phase
Ovarian Cancer Drug: Paclitaxel Drug: Bevacizumab Drug: Lurbinectedin Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 34 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1b of Lurbinectedin in Combination With Weekly Paclitaxel and Bevacizumab in Platinum-resistant Ovarian Cancer
Estimated Study Start Date : May 31, 2023
Estimated Primary Completion Date : July 31, 2024
Estimated Study Completion Date : July 31, 2026

Arm Intervention/treatment
Experimental: Dose Escalation and Dose Expansion
Pariticipants will be assigned to a dose level of combined paclitaxel, bevacizumab, and lurbinectedin
Drug: Paclitaxel
Given by (IV) vein
Other Name: Taxol

Drug: Bevacizumab
Given by (IV) vein
Other Names:
  • Avastin™
  • Anti-VEGF monoclonal antibody
  • rhuMAb-VEGF

Drug: Lurbinectedin
Given by (IV) vein

Primary Outcome Measures :
  1. Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 [ Time Frame: through study completion; an average of 1 year. ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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 bevacizumab 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 (alone or in combination with chemotherapy or other biological agents) 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 </= 28 days prior to cycle 1 day 1.
  7. Unstable cardiovascular function:

    1. ECG abnormalities requiring treatment, or
    2. congestive heart failure (CHF) of NYHA Class ≥3, or
    3. myocardial infarction (MI) within 3 months.
  8. 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.
  9. Any known history or evidence of hepatitis A, B, or C infection; or known to be positive for HCV RNA or HBsAg (HBV surface antigen); Known to be HIV seropositive
  10. Any underlying condition that would significantly interfere with the absorption of an oral medication.
  11. Grade >2 peripheral neuropathy at baseline (within 14 days prior to cycle 1 day 1).
  12. Serious psychiatric or medical conditions that could interfere with treatment;
  13. Participation in an investigational anti-cancer study within 3 weeks prior to Cycle 1 Day 1
  14. Concurrent therapy with approved or investigational anticancer therapeutic other than steroids.
  15. Patients with coagulation problems and active bleeding within 4 weeks prior to C1D1 (peptic ulcer, epistaxis, spontaneous bleeding)
  16. Patients with symptomatic brain lesions
  17. 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 three months after the last dose of study drug.

Examples of non-hormonal contraceptive methods with a failure rate of <1% per year include bilateral tubal ligation, male sterilization, established, proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.

  • Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation).
  • History of hemoptysis (1/2 teaspoon of bright red blood per episode) within 1 month of study enrollment for any tumor type.
  • Non-healing wound, ulcer or bone fracture.
  • Known hypersensitivity to lurbinectedin, paclitaxel, bevacizumab or excipients.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT05636111

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Contact: Shannon Westin, MD 713-794-4314

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United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Contact: Shannon Westin, MD    713-794-4314   
Principal Investigator: Shannon Westin, MD         
Sponsors and Collaborators
M.D. Anderson Cancer Center
Jazz Pharmaceuticals
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Principal Investigator: Shannon Westin, MD M.D. Anderson Cancer Center
Additional Information:
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Responsible Party: M.D. Anderson Cancer Center Identifier: NCT05636111    
Other Study ID Numbers: 2022-0231
NCI-2022-10037 ( Other Identifier: NCI-CTRP Clinical Trials Registry )
First Posted: December 5, 2022    Key Record Dates
Last Update Posted: June 5, 2023
Last Verified: June 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
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
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Angiogenesis Inhibitors
Angiogenesis Modulating Agents