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

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ClinicalTrials.gov Identifier: NCT03587311
Recruitment Status : Recruiting
First Posted : July 16, 2018
Last Update Posted : August 13, 2019
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This phase II trial studies the side effects of bevacizumab and anetumab ravtansine or paclitaxel in treating participants with ovarian, fallopian tube, or primary peritoneal cancer that does not respond to treatment. Monoclonal antibodies, such as bevacizumab and anetumab ravtansine, may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, 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 participants with ovarian, fallopian tube, or primary peritoneal cancer.

Condition or disease Intervention/treatment Phase
Fallopian Tube Endometrioid Adenocarcinoma High Grade Fallopian Tube Serous Adenocarcinoma High Grade Ovarian Serous Adenocarcinoma Ovarian Endometrioid Adenocarcinoma Platinum-Resistant Ovarian Carcinoma Primary Peritoneal High Grade Serous Adenocarcinoma Refractory Fallopian Tube Carcinoma Refractory Ovarian Carcinoma Refractory Primary Peritoneal Carcinoma Biological: Anetumab Ravtansine Biological: Bevacizumab Drug: Paclitaxel Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To assess the safety and tolerability of the combination of weekly anetumab ravtansine (anetumab) and bi-weekly bevacizumab.

II. To determine whether the progression free survival (PFS) of the combination weekly anetumab and bi-weekly bevacizumab is superior to weekly paclitaxel and bi-weekly bevacizumab.

SECONDARY OBJECTIVES:

I. To determine the overall response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1.

II. To evaluate the pharmacokinetic (PK) profiles of weekly anetumab in serum and in peripheral blood mononuclear cells (PBMCs).

III. To evaluate anti-drug antibody (ADA) titers (only for patients receiving anetumab).

IV. To evaluate mononuclear phagocyte system (MPS) function, Fc-gamma receptors (FcgammaRs), hormone and chemokine mediators.

V. To correlate the expression of CA125 (immunohistochemistry [IHC] & serum) with mesothelin expression in archival tissue and circulating megakaryocyte potentiating factor (MPF).

VI. To investigate blood-based angiome profiling as a potential biomarker. VII. To characterize the molecular profile of archival tumor tissue using the Oncomine panel, and explore whether genomic mutations such as BRCA1/2 and homologous repair deficiency status are associated with clinical outcome.

EXPLORATORY OBJECTIVES:

I. To assess tumor tissue-based VEGF-dependent gene expression signature as a biomarker of response.

OUTLINE:

PHASE I: Participants receive anetumab ravtansine intravenously (IV) over 1 hour on days 1, 8, 15, and 22 and bevacizumab over 30-90 minutes IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

PHASE II: Participants are randomized to 1 of 2 groups.

GROUP I: Participants receive anetumab ravtansine and bevacizumab as in Phase I.

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

After completion of study treatment, participants are followed up at 30-37 days and then every 8 weeks thereafter.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 96 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase 2 Study of Bevacizumab and Either Weekly Anetumab Ravtansine or Weekly Paclitaxel in Platinum-Resistant or Platinum Refractory Ovarian Cancer
Actual Study Start Date : June 29, 2018
Estimated Primary Completion Date : June 30, 2020
Estimated Study Completion Date : June 30, 2020


Arm Intervention/treatment
Experimental: GROUP I (anetumab ravtansine, bevacizumab)
Participants 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. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Biological: Anetumab Ravtansine
Given IV
Other Name: BAY 94-9343

Biological: Bevacizumab
Given IV
Other Names:
  • Anti-VEGF
  • Anti-VEGF Humanized Monoclonal Antibody
  • Anti-VEGF rhuMAb
  • Avastin
  • Bevacizumab awwb
  • Bevacizumab Biosimilar BEVZ92
  • Bevacizumab Biosimilar BI 695502
  • Bevacizumab Biosimilar CBT 124
  • Bevacizumab Biosimilar CT-P16
  • Bevacizumab Biosimilar FKB238
  • Bevacizumab Biosimilar HD204
  • Bevacizumab Biosimilar HLX04
  • Bevacizumab Biosimilar IBI305
  • Bevacizumab Biosimilar LY01008
  • Bevacizumab Biosimilar MIL60
  • Bevacizumab Biosimilar QL 1101
  • Bevacizumab Biosimilar RPH-001
  • Bevacizumab Biosimilar SCT501
  • BP102
  • BP102 Biosimilar
  • 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
  • Recombinant Humanized Anti-VEGF Monoclonal Antibody
  • rhuMab-VEGF
  • SCT501

Experimental: GROUP II (paclitaxel, bevacizumab)
Participants receive paclitaxel on days 1, 8, 15, and 22 and bevacizumab over 30-90 minutes IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Biological: Bevacizumab
Given IV
Other Names:
  • Anti-VEGF
  • Anti-VEGF Humanized Monoclonal Antibody
  • Anti-VEGF rhuMAb
  • Avastin
  • Bevacizumab awwb
  • Bevacizumab Biosimilar BEVZ92
  • Bevacizumab Biosimilar BI 695502
  • Bevacizumab Biosimilar CBT 124
  • Bevacizumab Biosimilar CT-P16
  • Bevacizumab Biosimilar FKB238
  • Bevacizumab Biosimilar HD204
  • Bevacizumab Biosimilar HLX04
  • Bevacizumab Biosimilar IBI305
  • Bevacizumab Biosimilar LY01008
  • Bevacizumab Biosimilar MIL60
  • Bevacizumab Biosimilar QL 1101
  • Bevacizumab Biosimilar RPH-001
  • Bevacizumab Biosimilar SCT501
  • BP102
  • BP102 Biosimilar
  • 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
  • Recombinant Humanized Anti-VEGF Monoclonal Antibody
  • rhuMab-VEGF
  • SCT501

Drug: Paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat




Primary Outcome Measures :
  1. Progression free survival (PFS) [ Time Frame: From the time of treatment start assessed up to 1 year ]
    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.


Secondary Outcome Measures :
  1. Response rate assessed using Response Evaluation Criteria in Solid Tumors [ Time Frame: Up to 1 year ]
    Only one, single, final analysis is planned and statistical significance will be defined at the alpha = 0.05 level. All tests will be two-sided and 95% confidence levels will be constructed for outcomes of interest.



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:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • 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+

    • For the run-in-phase 1, patients will not be selected based on the mesothelin expression
  • Patients with known brain metastases are not excluded from this clinical trial. Patients who received palliative radiation (for brain metastases) are eligible if they have been asymptomatic for at least 4 weeks without use of maintenance steroid therapy, and last received radiation at least 4 weeks prior to proposed start of therapy
  • Ability to understand and the willingness to sign a written informed consent document. Patients with Impaired Decision Making Capacity (IDMC) can have a Legally Authorized Representative sign on their behalf. Documentation, such as a Power of Attorney, must be presented in order for a substitute decision maker to be allowed

Exclusion Criteria:

  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • 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. 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
    • Myocardial infarction or unstable angina within 6 months
    • Serious and inadequately controlled cardiac arrhythmia
    • Significant vascular disease (e.g. aortic aneurysm, history of aortic dissection)
    • Clinically significant peripheral vascular disease
  • Evidence of bleeding diathesis or coagulopathy
  • Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
  • Current symptom of keratitis or retinopathy at >= grade 2
  • Resting electrocardiogram (ECG) with corrected QT interval by Fridericia (QTcF) > 470 msec or family history of long QT syndrome
  • History of bowel obstruction within 28 days from proposed start of treatment
  • History or evidence of arterial thrombotic or hemorrhagic disorders within 3 months before proposed start of treatment, non-healing wound, ulcer, or bone fracture
  • Prior use of weekly paclitaxel or bevacizumab in the platinum resistant (disease progression within 6 months of platinum based chemotherapy)/refractory (disease progression during or following the 3 months of the first line platinum based chemotherapy) setting
  • Known active human immunodeficiency virus (HIV) or hepatitis B or C infection

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 ClinicalTrials.gov identifier (NCT number): NCT03587311


Locations
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United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Site Public Contact    800-600-3606    info@siteman.wustl.edu   
Principal Investigator: Premal H. Thaker         
United States, Ohio
Ohio State University Comprehensive Cancer Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Site Public Contact    800-293-5066    Jamesline@osumc.edu   
Principal Investigator: David M. O'Malley         
United States, Tennessee
Vanderbilt University/Ingram Cancer Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Site Public Contact    800-811-8480      
Principal Investigator: Marta A. Crispens         
Canada, Ontario
University Health Network-Princess Margaret Hospital Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Site Public Contact    416-946-4501    clinical.trials@uhn.on.ca   
Principal Investigator: Stephanie Lheureux         
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Stephanie Lheureux University Health Network Princess Margaret Cancer Center LAO

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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT03587311     History of Changes
Other Study ID Numbers: NCI-2018-01503
NCI-2018-01503 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
10150 ( Other Identifier: University Health Network Princess Margaret Cancer Center LAO )
10150 ( Other Identifier: CTEP )
UM1CA186644 ( U.S. NIH Grant/Contract )
First Posted: July 16, 2018    Key Record Dates
Last Update Posted: August 13, 2019
Last Verified: April 2019

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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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Carcinoma
Adenocarcinoma
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Fallopian Tube Neoplasms
Carcinoma, Endometrioid
Cystadenocarcinoma, Serous
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Fallopian Tube Diseases
Endometrial Neoplasms
Uterine Neoplasms
Cystadenocarcinoma
Neoplasms, Cystic, Mucinous, and Serous
Paclitaxel
Maytansine
Albumin-Bound Paclitaxel
Bevacizumab
Antineoplastic Agents, Immunological
Endothelial Growth Factors