Paclitaxel and Bevacizumab With or Without Emactuzumab in Treating Patients With Platinum-Resistant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

NCT02923739 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2015-0647NCI-2016-01593
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 8

Brief Summary

This randomized phase II trial studies the side effects of paclitaxel and bevacizumab with or without emactuzumab and how well they work in treating patients with ovarian, fallopian tube, or primary peritoneal cancer that has come back after treatment with platinum chemotherapy. Monoclonal antibodies, such as emactuzumab, block tumor growth in different ways by targeting certain cells. 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. Bevacizumab may prevent the growth of new blood vessels that tumors need to grow. Giving emactuzumab with paclitaxel and bevacizumab may work better in treating ovarian, fallopian tube, or primary peritoneal cancer.

Conditions

Fallopian Tube Adenocarcinoma; Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Fallopian Tube Undifferentiated Carcinoma; Malignant Ovarian Brenner Tumor; Ovarian Adenocarcinoma; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Ovarian Undifferentiated Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma

Outcome Measures

Primary Outcomes (2)

• Part 1: To Evaluate the Safety of Administration of Paclitaxel, Bevacizumab and Emactuzumab Over 4 Weeks.

  Safety is defined as no required dose alterations during the first cycle (4 weeks) of therapy due to a grade 3 or greater related adverse event.

  Up to 4 weeks

• Part 2B: To Compare the Progression-free Survival (PFS) of Patients With Stable Disease Following Part 2A Randomized to Paclitaxel Plus Bevacizumab or to Paclitaxel, Bevacizumab Plus Emactuzumab.

  Will use a log-rank test.

  At 32 weeks

Study Arms (2)

Arm I (paclitaxel, bevacizumab)

ACTIVE COMPARATOR

Patients receive paclitaxel IV over 60 minutes on days 1, 8, 15, and 22 and bevacizumab IV over 90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Biological: Bevacizumab; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel

Arm II (paclitaxel, bevacizumab, emactuzumab)

EXPERIMENTAL

Patients receive paclitaxel and bevacizumab as in Arm I. Patients also receive emactuzumab IV over 30 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Biological: Bevacizumab; Biological: Emactuzumab; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel; Other: Pharmacological Study

Interventions

Bevacizumab BIOLOGICAL

Given IV

Also known as: Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin, Bevacizumab Biosimilar BEVZ92, Bevacizumab Biosimilar BI 695502, Bevacizumab Biosimilar CBT 124, Bevacizumab Biosimilar FKB238, Bevacizumab Biosimilar MIL60, Bevacizumab Biosimilar QL 1101, BEVACIZUMAB, LICENSE HOLDER UNSPECIFIED, 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

Arm I (paclitaxel, bevacizumab); Arm II (paclitaxel, bevacizumab, emactuzumab)

Emactuzumab BIOLOGICAL

Given IV

Also known as: RG-7155, RG7155, RO-5509554, RO5509554

Arm II (paclitaxel, bevacizumab, emactuzumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (paclitaxel, bevacizumab); Arm II (paclitaxel, bevacizumab, emactuzumab)

Paclitaxel DRUG

Given IV

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

Arm I (paclitaxel, bevacizumab); Arm II (paclitaxel, bevacizumab, emactuzumab)

Pharmacological Study OTHER

Correlative studies

Arm II (paclitaxel, bevacizumab, emactuzumab)

Eligibility Criteria

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

You may qualify if:

• Signed informed consent obtained prior to initiation of any study-specific procedures and treatment as confirmation of the patient's awareness and willingness to comply with the study requirements (inclusive of 2 biopsies, one at baseline and if they qualify, one pre-randomization for part 2B)
• Women 18 years of age or older
• Histologically confirmed and documented disease to include: adenocarcinoma NOS (not otherwise specified), clear cell adenocarcinoma, endometrioid adenocarcinoma, malignant Brenner's tumor, mixed epithelial carcinoma, mucinous adenocarcinoma, serous adenocarcinoma, transitional cell carcinoma, and undifferentiated carcinoma
• Patients must have platinum-resistant disease, (defined as progression within \< 6 months from completion of a minimum of 4 platinum therapy cycles (+ 7 days); the date should be calculated from the last administered dose of platinum therapy)
• Patients must have disease that is measurable according to RECIST 1.1 or assessable according to the GCIG CA-125 criteria and require chemotherapy treatment; part 1: patients must have one or more measurable target lesion; part 2: patients must have two or more measurable target lesions; measurable disease is defined at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded); each 'target' lesion must be \>= 20 mm when measured by conventional techniques, including palpation, plain x-ray, computed tomography (CT), and magnetic resonance imaging (MRI), or \>= 10 mm when measured by spiral CT
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
• Newly obtained core or excisional biopsy of a tumor lesion for part 2A and if they qualify, one pre-randomization biopsy for part 2B
• Absolute neutrophil count \>= 1,500/mcL
• Platelets \>= 100,000/mcL
• Hemoglobin \>=9 g/dL or \>= 5.6 mmol/L
• Creatinine clearance \>= 60 mL/min for subject with creatinine levels \> 1.5 X institutional upper limit of normal (ULN)
• Total bilirubin =\< 1.5 X ULN OR direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 ULN
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGOT\]) =\< 2.5 X ULN OR =\< 5 X ULN for subjects with liver metastases
• International normalized ratio (INR)/prothrombin time (PT) =\< 1.5 X ULN (unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time \[PTT\] is within therapeutic range of intended use of anticoagulants)
• PTT =\< 1.5 X ULN (unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants)

You may not qualify if:

• Patients who have disease progression prior to completion of intended frontline therapy, including patients demonstrating disease progression after interval cytoreduction
• Non-epithelial, including malignant mixed Mullerian tumors
• Ovarian tumors with low malignant potential (i.e. borderline tumors)
• For part 2 patients only: History of other clinically active malignancy within 5 years of enrollment, except for tumors with a negligible risk for metastasis or death, such as adequately controlled basal-cell carcinoma or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix or breast, or early stage endometrial cancer (stage IA/B, grade 1 or 2, endometrioid histology)
• Previous treatment with \> 2 anticancer regimens for ovarian cancer
• Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 3 weeks prior to initiation of study treatment, with the following exceptions: hormone-replacement therapy or oral contraceptives; tyrosine kinase inhibitors (TKIs) that have been discontinued \> 7 days prior to cycle 1, day 1; screening scans must be obtained after discontinuation of prior TKIs
• Any prior radiotherapy to the pelvis or abdomen
• Surgical procedure (including open biopsy, surgical resection, wound revision, or any other major surgery involving entry into a body cavity) or significant traumatic injury within 28 days prior to study enrollment, or anticipation of need for major surgical procedure during the course of the study; minor surgical procedures including placement of a vascular access device, within 2 days of the first study treatment
• Previous exposure to murine CA-125 antibody (only applicable to those patients with non-measurable disease by RECIST)
• Current or recent (within 10 days prior to the first study drug dose) chronic daily treatment with aspirin (\> 325 mg/day)
• Current or recent treatment with another investigational drug within 30 days of first study treatment dosing or earlier participation in this study
• Treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF agents within 2 weeks prior to cycle 1, day 1; patients who have received acute and/or lowrolment, or anticipation of need for major surgical, a one-time dose of dexamethasone for nausea or chronic use of =\< 10 mg/day of prednisone or dose-equivalent corticosteroid) may be enrolled in the study after discussion with and approval by the medical monitor; the use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) is allowed; prior corticosteroids as anti-cancer therapy within a minimum of 14 days of first receipt of study drug
• Received therapeutic oral or IV antibiotics within 2 weeks prior to cycle 1, day 1; patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible
• Patients with urine dipstick for proteinuria \> 2+; patients with \>= 2+ proteinuria on baseline dipstick analysis should undergo a 24-hour urine collection and must demonstrate =\< 1 g of protein in the 24-hour urine; alternatively, proteinuria testing can be performed according to local standards
• Patients with known auto-immune disease

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (8)

MD Anderson Cancer Center at Cooper-Voorhees

Voorhees Township, New Jersey, 08043, United States

Location

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, 75390, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

The Woman's Hospital of Texas

Houston, Texas, 77054, United States

Location

MD Anderson Regional Care Center-Katy

Houston, Texas, 77094, United States

Location

MD Anderson Regional Care Center-Bay Area

Nassau Bay, Texas, 77058, United States

Location

MD Anderson Regional Care Center-Sugar Land

Sugar Land, Texas, 77478, United States

Location

MD Anderson Regional Care Center-The Woodlands

The Woodlands, Texas, 77384, United States

Location

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Brenner Tumor; Fallopian Tube Neoplasms; Ovarian Neoplasms

Interventions

Bevacizumab; Immunoglobulin G; Disulfides; emactuzumab; Paclitaxel; Taxes

Condition Hierarchy (Ancestors)

Neoplasms, Fibroepithelial; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; 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; Gonadal Disorders; Endocrine System Diseases; Neoplasms by Site; Fallopian Tube Diseases; Endocrine Gland Neoplasms

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

Results Point of Contact

• Title: Dr. Anil Sood
• Organization: M D Anderson Cancer Center

asood@mdanderson.org

713-745-5266

Study Officials

• Anil K. Sood, MD

  M.D. Anderson Cancer Center

  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: September 30, 2016
• First Posted: October 5, 2016
• Study Start: May 5, 2017
• Primary Completion: September 27, 2022
• Study Completion: September 27, 2022
• Last Updated: March 13, 2024
• Results First Posted: October 10, 2023

Record last verified: 2024-03

Locations

US (8)