Evaluation of Weekly Ixabepilone With or Without Biweekly Bevacizumab

NCT03093155 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 2000020232
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 2

Brief Summary

This is a randomized, two-arm, open-label Phase II multicenter study designed to examine the effects of adding bevacizumab to ixabepilone for the treatment of patients who have recurrent or persistent platinum-resistant/refractory epithelial (non-mucinous) ovarian, fallopian tube, or primary peritoneal cancer. Its primary objective is to assess whether adding bevacizumab to ixabepilone improves progression-free survival in its target population. Study participants will be stratified by (a) study site and (b) previous receipt of bevacizumab prior to randomization.

Conditions

Epithelial Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS) Differences Between Ixabepilone Alone and Ixabepilone + Bevacizumab

  Progression-free survival (PFS), the primary endpoint, will be defined as the length of time from randomization to disease recurrence, disease progression, or death for any reason. The timeframe was updated upon results entry.

  Up to 37 months

Secondary Outcomes (5)

• Objective Response Rate (ORR)

  Up to 37 months

• Overall Survival (OS) Differences Between Ixabepilone Alone and Ixabepilone + Bevacizumab

  Up to 37 months

• Number of Participants With Treatment Related SAEs

  Up to 37 months

• Differences in Response to the Combination of Ixabepilone and Bevacizumab in Relationship to Previous Treatment With Bevacizumab and Taxanes

  Up to 41 months

• Durable Disease Control Rate (DDCR) Differences Between Ixabepilone Alone and Ixabepilone + Bevacizumab

  5 Years

Study Arms (2)

Ixabepilone

ACTIVE COMPARATOR

Ixabepilone 20 mg/m2 days 1, 8, 15 Q 28 days

Drug: Ixabepilone

Ixabepilone + Bevacizumab

EXPERIMENTAL

Ixabepilone 20 mg/m2 days 1, 8, 15 \+ Bevacizumab 10 mg/kg days 1, 15 Q 28 days

Drug: Ixabepilone; Drug: Bevacizumab

Interventions

Ixabepilone DRUG

Ixabepilone will be administered at 20 mg/m2 intravenously days 1, 8, 15 of a 28-day cycle over one hour. Treatment will continue until progression, death, or prohibitive side effects. If any patient has a complete response, patient may stop treatment after 2 additional consolidation cycles following documented complete response

Also known as: Ixempra

Ixabepilone; Ixabepilone + Bevacizumab

Bevacizumab DRUG

Bevacizumab will be administered at 10 mg/kg intravenously days 1, 15 of a 28-day cycle over one hour. Bevacizumab will be infused after ixabepilone. The first dose of bevacizumab will be administered intravenously over 90 minutes; the second dose may be administered over 60 minutes if no prior reaction to previous infusion; subsequent doses may be administered over 30 minutes if no prior reaction to previous infusion. Treatment will continue until progression, death, or prohibitive side effects. If any patient has a complete response, patient may stop treatment after 2 additional consolidation cycles following documented complete response.

Also known as: Avastin

Ixabepilone + Bevacizumab

Eligibility Criteria

• Age: 18 Years - 100 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have platinum-resistant/refractory (i.e., platinum-free interval \<6 months) recurrent or persistent histologically confirmed epithelial (non-mucinous) ovarian, fallopian tube, or primary peritoneal cancer.
• Patients may have serous, endometrioid, clear cell, carcinosarcoma, or transitional cell/malignant Brenner, mixed, or undifferentiated histologies.
• Patients must have specimen available for immunohistochemistry for class III β-tubulin status; recurrent tumor specimen is preferred, though this may be performed on primary tumor if no recurrent tumor is available.
• All patients must have measurable disease. Measurable disease is defined as lesions that can be measured by physical examination or by means of medical imaging techniques. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded). Each lesion must be ≥ 20 mm when measured by conventional techniques, including palpation or plain x-ray, or ≥ 10 mm when measured by spiral CT and/or MRI. Ascites and pleural effusions are not to be considered measurable disease.
• Patients must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST v1.1 Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy.
• At the time of initial surgery, patients may have been optimally (\<1 cm diameter residual disease) or sub-optimally (≥1 cm diameter of residual disease) debulked.
• Patients with measurable recurrent disease of any previous stage (I-IV) are eligible to enrollment.
• The diagnosis must be histologically confirmed by a gynecologic pathologist.
• Patients must have adequate bone marrow, kidney, and liver function:
• Absolute neutrophil count greater than or equal to 1500 cells/mm3
• Platelets greater than or equal to 100,000/uL
• Renal function: creatinine less than or equal to 2.0 mg/dL
• Hepatic function: Bilirubin ≤ 1.5 X laboratory normal
• SGOT/SGPT ≤ 3 X laboratory normal.
• Patients must have an ECOG performance status of 0-2.

You may not qualify if:

• Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancers, are excluded if there is any evidence of other malignancy present within the last five years. Patients are also excluded if their previous cancer treatment contraindicates this protocol therapy.
• Patients who have a significant history of cardiac disease, i.e., uncontrolled hypertension, unstable angina, uncontrolled congestive heart failure, or uncontrolled arrhythmias within 6 months of registration (NYHA classification III-IV).
• Patients with any unstable medical issue (including cardiac issues as above, active treatment for symptomatic pulmonary embolism, CVA, renal or hepatic insufficiency, active infection/sepsis requiring intravenous antibiotics). In patients who have undergone surgery, 28 days should elapse before initiation and the surgical site should be adequately healed.
• Known brain/leptomeningeal involvement of the disease, active neurological disease such as uncontrolled seizure disorder or moderate to severe dementia.
• Patients who have received prior therapy with any covalent irreversible anti-angiogenic tyrosine kinase inhibitor (e.g., vandetanib).
• Patients known to be seropositive for human immunodeficiency virus (HIV) and active hepatitis, even if liver function studies are in the eligible range.
• Known hemorrhagic diathesis or active bleeding disorder, including platelet count \<100,000/uL, or inadequate granulocytes, including an absolute neutrophil count \<1500 cells/mm.
• Any hypersensitivity to Cremophor® EL or polyoxyethylated castor oil.
• CTCAE grade 2 or higher peripheral neuropathy.

Sponsors & Collaborators

• Yale University: lead
• R-Pharm US LLC.: collaborator

Study Sites (2)

Smilow Cancer Hospital at Yale New Haven

New Haven, Connecticut, 06510, United States

Location

Marlene & Stewart Greenebaum Comprehensive Cancer Center, University of Maryland

Baltimore, Maryland, 21201, United States

Location

Related Publications (3)

• Roque DM, Siegel ER, Buza N, Bellone S, Silasi DA, Huang GS, Andikyan V, Clark M, Azodi M, Schwartz PE, Rao GG, Reader JC, Hui P, Tymon-Rosario JR, Harold J, Mauricio D, Zeybek B, Menderes G, Altwerger G, Ratner E, Santin AD. Randomised phase II trial of weekly ixabepilone +/- biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer. Br J Cancer. 2022 Jun;126(12):1695-1703. doi: 10.1038/s41416-022-01717-6. Epub 2022 Feb 11.

  PMID: 35149854 RESULT

• Roque DM, Siegel ER, Buza N, Bellone S, Huang GS, Altwerger G, Andikyan V, Clark M, Azodi M, Schwartz PE, Rao GG, Ratner E, Santin AD. Randomized phase II trial of weekly ixabepilone +/- biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer (NCT03093155): Updated survival and subgroup analyses. BJC Rep. 2024 Jun 20;2(1):43. doi: 10.1038/s44276-024-00067-5.

  PMID: 39516558 DERIVED

• Gaitskell K, Rogozinska E, Platt S, Chen Y, Abd El Aziz M, Tattersall A, Morrison J. Angiogenesis inhibitors for the treatment of epithelial ovarian cancer. Cochrane Database Syst Rev. 2023 Apr 18;4(4):CD007930. doi: 10.1002/14651858.CD007930.pub3.

  PMID: 37185961 DERIVED

MeSH Terms

Conditions

Carcinoma, Ovarian Epithelial; Fallopian Tube Neoplasms

Interventions

ixabepilone; Bevacizumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Ovarian Neoplasms; 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; Fallopian Tube Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Alessandro Santin, MD
• Organization: Yale School of Medicine/Yale Cancer Center

alessandro.santin@yale.edu

(203) 737-4450

Study Officials

• Alessandro D. Santin, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2017
• First Posted: March 28, 2017
• Study Start: April 3, 2017
• Primary Completion: December 29, 2022
• Study Completion: December 29, 2022
• Last Updated: May 14, 2024
• Results First Posted: May 14, 2024

Record last verified: 2024-04

Locations

US (2)