Bevacizumab and Anetumab Ravtansine or Paclitaxel in Treating Patients With Refractory Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

NCT03587311 | Active Not Recruiting Phase 2 DMC FDA Drug

• 4 other identifiers: NCI-2018-01503PHL-09810150UM1CA186644
• Study Type: interventional
• Target: 96
• Locations: 2 countries
• Sites: 23

Brief Summary

This phase II trial studies the side effects of bevacizumab and anetumab ravtansine or paclitaxel in treating patients with ovarian, fallopian tube, or primary peritoneal cancer that does not respond to treatment (refractory). Bevacizumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Anetumab ravtansine is a drug that targets a protein in the body called mesothelin, which can be found in some ovarian, pancreatic and other tumors. Chemotherapy drugs, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving bevacizumab and anetumab ravtansine or paclitaxel may work better in treating patients with ovarian, fallopian tube, or primary peritoneal cancer.

Conditions

Primary Peritoneal High Grade Serous Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube High Grade Serous Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian High Grade Serous Adenocarcinoma; Platinum-Resistant Fallopian Tube Carcinoma; Platinum-Resistant Ovarian Carcinoma; Platinum-Resistant Primary Peritoneal Carcinoma

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS)

  PFS will be estimated using the Kaplan-Meier method and compared between groups with log rank test. Summary statistics will be provided, such as the median, 6-month and estimates, along with 95% confidence intervals. Plots will also be constructed which show the PFS estimate and 95% confidence intervals.

  From the time of treatment start assessed up to 1 year

Secondary Outcomes (1)

• Response rate assessed using Response Evaluation Criteria in Solid Tumors

  Up to 1 year

Study Arms (2)

GROUP I (anetumab ravtansine, bevacizumab)

EXPERIMENTAL

Patients receive anetumab ravtansine IV over 1 hour on days 1, 8, 15, and 22 and bevacizumab over 30-90 minutes IV on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Biological: Anetumab Ravtansine; Biological: Bevacizumab

GROUP II (paclitaxel, bevacizumab)

EXPERIMENTAL

Patients receive paclitaxel on days 1, 8, 15, and 22 and bevacizumab over 30-90 minutes IV on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Biological: Bevacizumab; Drug: Paclitaxel

Interventions

Anetumab Ravtansine BIOLOGICAL

Given IV

Also known as: BAY 94-9343

GROUP I (anetumab ravtansine, bevacizumab)

Bevacizumab BIOLOGICAL

Given IV

Also known as: ABP 215, ABP-215, ABP215, Alymsys, Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF Monoclonal Antibody SIBP04, Anti-VEGF rhuMAb, Avastin, Avzivi, Aybintio, BAT 1706, BAT-1706, BAT1706, BAT1706 Biosimilar, Bevacizumab awwb, Bevacizumab Biosimilar ABP 215, Bevacizumab Biosimilar BAT1706, Bevacizumab Biosimilar BEVZ92, Bevacizumab Biosimilar BI 695502, Bevacizumab Biosimilar CBT 124, Bevacizumab Biosimilar CT-P16, Bevacizumab Biosimilar FKB238, Bevacizumab Biosimilar GB-222, Bevacizumab Biosimilar HD204, Bevacizumab Biosimilar HLX04, Bevacizumab Biosimilar IBI305, Bevacizumab Biosimilar LY01008, Bevacizumab Biosimilar MB02, Bevacizumab Biosimilar MIL60, Bevacizumab Biosimilar Mvasi, Bevacizumab Biosimilar MYL-1402O, Bevacizumab Biosimilar QL 1101, Bevacizumab Biosimilar QL1101, Bevacizumab Biosimilar RPH-001, Bevacizumab Biosimilar SCT501, Bevacizumab Biosimilar Zirabev, Bevacizumab-adcd, Bevacizumab-awwb, Bevacizumab-aybi, Bevacizumab-bvzr, Bevacizumab-equi, Bevacizumab-maly, Bevacizumab-onbe, Bevacizumab-tnjn, BP102, BP102 Biosimilar, CT P16, CT-P16, CTP16, Equidacent, FKB 238, FKB-238, FKB238, HD204, Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer, MB 02, MB-02, MB02, Mvasi, MYL-1402O, Onbevzi, Oyavas, PF 06439535, PF-06439535, PF06439535, QL1101, Recombinant Humanized Anti-VEGF Monoclonal Antibody, rhuMab-VEGF, SCT501, SIBP 04, SIBP-04, SIBP04, Vegzelma, Zirabev

GROUP I (anetumab ravtansine, bevacizumab); GROUP II (paclitaxel, bevacizumab)

Paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

GROUP II (paclitaxel, bevacizumab)

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically or cytologically confirmed high grade serous or high grade endometrioid ovarian, fallopian tube, primary peritoneal cancer
• Patients must have platinum resistant (platinum-free interval \< 6 months) or platinum refractory disease as per Gynecological Cancer Intergroup (GCIC) criteria
• Patients must have radiologic evidence of disease progression
• Criteria only for the randomized phase 2 part: patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>= 20 mm with conventional techniques or as \>= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• Leukocytes \>= 3 x 10\^9/L
• Absolute neutrophil count \>= 1.5 x 10\^9/L
• Platelets \>= 100 x 10\^9/L
• Total bilirubin =\< upper limit of normal (ULN) (except in Gilbert's syndrome)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal (ULN)
• Serum creatinine =\< 1.5 x ULN OR creatinine clearance \>= 50 mL/min/1.73 m\^2 for patients with creatinine levels above 1.5 x institutional normal (using the Cockcroft Gault formula)
• Urine protein / creatinine ratio (UPCR) =\< 1
• Ongoing prior toxicities related to previous treatments must be recovered to \< grade 2 at the time of registration (with the exception of alopecia, grade 2 peripheral neuropathy or lymphopenia)
• Criteria only for the randomized phase 2 part: mesothelin screen positive determined from archival tumor tissue and to be performed centrally. MSLN-positive is defined as \>= 30% of tumor cells with membrane staining intensities \>= 2+. If an archival tumor specimen is unavailable, or unsuitable for mesothelin testing, a pre-treatment fresh tumor biopsy is required
• For the run-in-phase 1, patients will not be selected based on the mesothelin expression

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
• Patients who are receiving any other investigational agents
• History of severe allergic reactions attributed to compounds of similar chemical or biologic composition to bevacizumab, anetumab ravtansine or paclitaxel
• Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list or medical reference texts such as the Physicians' Desk Reference may also provide this information. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product. Strong inhibitors and inducers of CYP3A4 are prohibited within 2 weeks before the start of and during treatment. Strong inhibitors and inducers of CYP2C8 should be used with caution; the PI of the study is to be consulted regarding their use
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study because of the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother, breastfeeding should be discontinued during the study and for at least 6 months after last dose of study drugs. These potential risks may also apply to other agents used in this study. Women of child-bearing potential who do not agree to use adequate contraceptive measures during study therapy and for at least 6 months after the completion of study therapy will be excluded. Should a patient become pregnant or suspect she is pregnant while she is participating in this study, the patient should inform the treating physician immediately
• Serious or non-healing wound, ulcer or bone fracture
• History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to day 1
• Invasive procedures defined as follows:
• Major surgical procedure or significant traumatic injury within 28 days prior to day 1 therapy, or open biopsy within 7 days prior to day 1 therapy
• Anticipation of need for major surgical procedures during the course of the study
• Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to day 1
• Patients with clinically significant cardiovascular disease are excluded
• Inadequately controlled hypertension (HTN) (systolic blood pressure \[SBP\] \> 160 mmHg and/or diastolic blood pressure \[DBP\] \> 90 mmHg despite antihypertensive medication)
• History of cerebrovascular accident (CVA) within 6 months

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (23)

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

Location

UCHealth University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

UM Sylvester Comprehensive Cancer Center at Coral Gables

Coral Gables, Florida, 33146, United States

Location

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida, 33442, United States

Location

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136, United States

Location

UM Sylvester Comprehensive Cancer Center at Plantation

Plantation, Florida, 33324, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

HaysMed

Hays, Kansas, 67601, United States

Location

The University of Kansas Cancer Center - Olathe

Olathe, Kansas, 66061, United States

Location

Mercy Hospital Pittsburg

Pittsburg, Kansas, 66762, United States

Location

Salina Regional Health Center

Salina, Kansas, 67401, United States

Location

University of Kansas Health System Saint Francis Campus

Topeka, Kansas, 66606, United States

Location

University of Kansas Hospital-Westwood Cancer Center

Westwood, Kansas, 66205, United States

Location

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Weisberg Cancer Treatment Center

Farmington Hills, Michigan, 48334, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States

Location

University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, 53792, United States

Location

University Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Interventions

anetumab ravtansine; Bevacizumab; Immunoglobulin G; Disulfides; Paclitaxel; Taxes

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoglobulin Isotypes; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations

Study Officials

• Stephanie Lheureux

  University Health Network Princess Margaret Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: July 13, 2018
• First Posted: July 16, 2018
• Study Start: October 12, 2018
• Primary Completion (Estimated): October 21, 2026
• Study Completion (Estimated): October 21, 2026
• Last Updated: April 13, 2026

Record last verified: 2026-04

Locations

CA (1); US (22)