Intensity-Modulated Radiation Therapy, Cisplatin, and Bevacizumab Followed by Carboplatin and Paclitaxel in Treating Patients Who Have Undergone Surgery for Endometrial Cancer

NCT ID: NCT01005329

Last Updated: 2018-03-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-11-06
• Study Completion Date: 2013-09-22

Brief Summary

This phase II trial studies the side effects of giving intensity-modulated radiation therapy together with cisplatin and bevacizumab followed by carboplatin and cisplatin and to see how well they work in treating patients who have undergone surgery for high-risk endometrial cancer. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy, such as cisplatin, carboplatin, and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block the ability of tumor cells to grow and spread. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving intensity-modulated radiation therapy together with chemotherapy and bevacizumab after surgery may kill any tumor cells that remain after surgery.

Detailed Description

PRIMARY OBJECTIVE:

I. To assess the treatment-related, grade 3+, non-hematologic adverse-event rate within 90 days from the start of treatment with concurrent intensity-modulated radiotherapy, cisplatin, and bevacizumab followed by carboplatin and paclitaxel in patients with high-risk endometrial cancer.

SECONDARY OBJECTIVES:

I. To evaluate treatment-related adverse events occurring within 1 year from the start of treatment.

II. To evaluate all treatment-related adverse events. III. To evaluate disease-free and overall survival. IV. To evaluate local, regional, and distant failure.

OUTLINE:

Patients undergo pelvic intensity-modulated radiotherapy (IMRT) once daily, 5 days a week, for 5 weeks. Patients may also undergo optional nodal boost radiotherapy and/or vaginal brachytherapy boost. Patients also receive concurrent cisplatin intravenously (IV) over 1 hour on days 1 and 29 and bevacizumab IV over 30-90 minutes on days 1, 15, and 29. Beginning 4-6 weeks after completing IMRT, cisplatin, and bevacizumab, patients receive carboplatin IV over 1 hour and paclitaxel IV over 3 hours on day 1. Treatment with carboplatin and paclitaxel repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

Conditions

Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Serous Adenocarcinoma; Stage IA Uterine Corpus Cancer AJCC v7; Stage IB Uterine Corpus Cancer AJCC v7; Stage II Uterine Corpus Cancer AJCC v7; Stage IIIA Uterine Corpus Cancer AJCC v7; Stage IIIB Uterine Corpus Cancer AJCC v7; Stage IIIC Uterine Corpus Cancer AJCC v7; Stage IVA Uterine Corpus Cancer AJCC v7; Stage IVB Uterine Corpus Cancer AJCC v7

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (IMRT, cisplatin,bevacizumab,carboplatin,paclitaxel)

Patients undergo pelvic IMRT once daily, 5 days a week, for 5 weeks. Patients may also undergo optional nodal boost radiotherapy and/or vaginal brachytherapy boost. Patients also receive concurrent cisplatin IV over 1 hour on days 1 and 29 and bevacizumab IV over 30-90 minutes on days 1, 15, and 29. Beginning 4-6 weeks after completing IMRT, cisplatin, and bevacizumab, patients receive carboplatin IV over 1 hour and paclitaxel IV over 3 hours on day 1. Treatment with carboplatin and paclitaxel repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

Bevacizumab

Intervention Type: BIOLOGICAL

Given IV

Carboplatin

Intervention Type: DRUG

Given IV

Cisplatin

Intervention Type: DRUG

Given IV

Intensity-Modulated Radiation Therapy

Intervention Type: RADIATION

Undergo IMRT

Paclitaxel

Intervention Type: DRUG

Given IV

Interventions

Bevacizumab

Given IV

Intervention Type: BIOLOGICAL

Carboplatin

Given IV

Intervention Type: DRUG

Cisplatin

Given IV

Intervention Type: DRUG

Intensity-Modulated Radiation Therapy

Undergo IMRT

Intervention Type: RADIATION

Paclitaxel

Given IV

Intervention Type: DRUG

Other Intervention Names

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, 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; Blastocarb; Carboplat; Carboplatin Hexal; Carboplatino; Carbosin; Carbosol; Carbotec; CBDCA; Displata; Ercar; JM-8; Nealorin; Novoplatinum; Paraplatin; Paraplatin AQ; Paraplatine; Platinwas; Ribocarbo; Abiplatin; Blastolem; Briplatin; CDDP; Cis-diammine-dichloroplatinum; Cis-diamminedichloridoplatinum; Cis-diamminedichloro Platinum (II); Cis-diamminedichloroplatinum; Cis-dichloroammine Platinum (II); Cis-platinous Diamine Dichloride; Cis-platinum; Cis-platinum II; Cis-platinum II Diamine Dichloride; Cismaplat; Cisplatina; Cisplatinum; Cisplatyl; Citoplatino; Citosin; Cysplatyna; DDP; Lederplatin; Metaplatin; Neoplatin; Peyrone's Chloride; Peyrone's Salt; Placis; Plastistil; Platamine; Platiblastin; Platiblastin-S; Platinex; Platinol; Platinol- AQ; Platinol-AQ; Platinol-AQ VHA Plus; Platinoxan; Platinum; Platinum Diamminodichloride; Platiran; Platistin; Platosin; IMRT; Intensity Modulated RT; Intensity-Modulated Radiotherapy; Anzatax; Asotax; Bristaxol; Praxel; Taxol; Taxol Konzentrat

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed endometrial cancer, including 1 of the following cellular types:

• Endometrioid endometrial adenocarcinoma
• Clear cell carcinoma
• Papillary serous adenocarcinoma
• Adenosquamous cell carcinoma
• Other adenocarcinoma variant
• No carcinosarcoma
• Meets 1 of the following criteria:

• Grade 3 carcinoma with > 50% myometrial invasion (stage IC or IIA) (all papillary serous or clear cell carcinoma will be considered grade 3)
• Grade 2 or 3 carcinoma with any cervical stromal invasion (stage IIB)
• Known extra-uterine disease confined to the pelvis (stage III or IVA)

• Patients with stage III or IVA disease must have undergone computed tomography (CT) scan or positron emission tomography (PET)/CT scan of the abdomen and pelvis within the past 56 days
• Has undergone hysterectomy (i.e., total abdominal, vaginal, robotic-assisted, radical, or laparoscopic-assisted vaginal hysterectomy) and bilateral salpingo-oophorectomy within the past 56 days
• No positive common iliac or positive para-aortic nodal disease (defined as lymph nodes ? 2 cm in any dimension on CT scan or biopsy) or positive peritoneal cytology
• No evidence of metastatic extrauterine disease, gross or residual disease (not including pelvic nodal disease), or distant metastases
• Zubrod performance status 0-1
• Absolute neutrophil count (ANC) ? 1,500/mm^3 (without growth factor support)
• Platelet count ? 100,000/mm^3
• Hemoglobin ? 10 g/dL (transfusion allowed)
• Total bilirubin ? 1.5 times upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ? 2 times ULN
• Serum creatinine ? 1.5 mg/dL
• Urine protein:creatinine ratio ? 0.5 OR urine protein < 1,000 mg on 24-hour urine collection
• International normalized ratio (INR) < 1.5 (for patients treated with warfarin within the past 14 days)
• Not nursing
• No neuropathy ? Common Terminology Criteria for Adverse Events (CTCAE) grade 1
• No ototoxicity > CTCAE grade 2
• No serious, active comorbidity, including any of the following:

• Unstable angina and/or New York Heart Association (NYHA) class II-IV congestive heart failure requiring hospitalization within the past 12 months
• Transmural myocardial infarction within the past 12 months
• Acute bacterial or fungal infection requiring IV antibiotics
• Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy
• Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
• Acquired immune deficiency syndrome (AIDS) based upon current Center for Disease Control (CDC) definition (human immunodeficiency virus [HIV] testing is not required)
• Active gastrointestinal (GI) ulcers, GI bleeding, inflammatory bowel disease, or GI obstruction
• Inadequately controlled hypertension, defined as systolic blood pressure (BP) > 150 mm Hg and/or diastolic BP > 90 mm Hg on antihypertensive medications
• Significant vascular disease, including aortic aneurysm, aortic dissection, or arteriovenous malformation within the past 12 months
• Serious cardiac arrhythmia on medication (well-controlled atrial fibrillation on medication allowed)
• Serious non-healing wound, ulcer, or bone fracture
• No history of hypertensive crisis or hypertensive encephalopathy
• No stroke/cerebrovascular event within the past 12 months
• No arterial thromboembolic events, including transient ischemic attack or clinically symptomatic peripheral artery disease within the past 12 months
• No abdominal fistula, GI perforation, or intra-abdominal abscess within the past 6 months
• No other invasive malignancies within the past 3 years other than nonmelanomatous skin cancer
• No significant trauma within the past 28 days
• No mental status changes or bladder problems that would preclude the ability to comply with bladder-filling instructions
• No mental or psychiatric illness that would preclude giving informed consent
• No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
• No prior allergic reaction to bevacizumab, cisplatin, carboplatin, or paclitaxel
• No concurrent erythropoietin, St. John's wort, therapeutic anticoagulants, aminoglycoside antibiotics, or amifostine
• No prior organ transplantation
• No prior external-beam radiotherapy to the pelvis resulting in overlapping of radiotherapy fields
• No prior systemic chemotherapy for uterine cancer

• Prior chemotherapy for a different cancer is allowed
• No prior therapy with anti-vascular endothelial growth factor (VEGF) compounds
• More than 28 days since prior major surgical procedure requiring open biopsy incision
• No concurrent surgery (except for vascular access device placement or procedures that do not require significant incision)
• No concurrent warfarin at doses > 1 mg/day

• Concurrent prophylactic low molecular weight heparin allowed

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Radiation Therapy Oncology Group

NETWORK

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Akila Viswanathan

Role: PRINCIPAL_INVESTIGATOR

Radiation Therapy Oncology Group

Locations

Alta Bates Summit Medical Center-Herrick Campus

Berkeley, California, United States

John Muir Medical Center-Walnut Creek

Walnut Creek, California, United States

Penrose-Saint Francis Healthcare

Colorado Springs, Colorado, United States

Poudre Valley Hospital

Fort Collins, Colorado, United States

Christiana Care Health System-Christiana Hospital

Newark, Delaware, United States

Baptist MD Anderson Cancer Center

Jacksonville, Florida, United States

Integrated Community Oncology Network-Southside Cancer Center

Jacksonville, Florida, United States

University of Florida Health Science Center - Jacksonville

Jacksonville, Florida, United States

Baptist Medical Center South

Jacksonville, Florida, United States

Integrated Community Oncology Network-Florida Cancer Center Beaches

Jacksonville Beach, Florida, United States

21st Century Oncology-Orange Park

Orange Park, Florida, United States

21st Century Oncology-Palatka

Palatka, Florida, United States

Bay Medical Center

Panama City, Florida, United States

Integrated Community Oncology Network-Flager Cancer Center

Saint Augustine, Florida, United States

Northwestern University

Chicago, Illinois, United States

John H Stroger Jr Hospital of Cook County

Chicago, Illinois, United States

Saint Vincent Anderson Regional Hospital/Cancer Center

Anderson, Indiana, United States

Saint Vincent Hospital and Health Care Center

Indianapolis, Indiana, United States

Kansas City NCI Community Oncology Research Program

Prairie Village, Kansas, United States

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, United States

Central Maryland Radiation Oncology in Howard County

Columbia, Maryland, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

Henry Ford Hospital

Detroit, Michigan, United States

West Michigan Cancer Center

Kalamazoo, Michigan, United States

Elliot Hospital

Manchester, New Hampshire, United States

Stony Brook University Medical Center

Stony Brook, New York, United States

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Summa Akron City Hospital/Cooper Cancer Center

Akron, Ohio, United States

Summa Barberton Hospital

Barberton, Ohio, United States

Flower Hospital

Sylvania, Ohio, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Paoli Memorial Hospital

Paoli, Pennsylvania, United States

Radiation Therapy Oncology Group

Philadelphia, Pennsylvania, United States

Lankenau Medical Center

Wynnewood, Pennsylvania, United States

M D Anderson Cancer Center

Houston, Texas, United States

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, United States

Wheeling Hospital/Schiffler Cancer Center

Wheeling, West Virginia, United States

Froedtert and the Medical College of Wisconsin

Milwaukee, Wisconsin, United States

London Regional Cancer Program

London, Ontario, Canada

McGill University Department of Oncology

Montreal, Quebec, Canada

Pamela Youde Nethersole Eastern Hospital

Chai Wan, , Hong Kong

Countries

United States; Canada; Hong Kong

References

Viswanathan AN, Moughan J, Miller BE, Xiao Y, Jhingran A, Portelance L, Bosch WR, Matulonis UA, Horowitz NS, Mannel RS, Souhami L, Erickson BA, Winter KA, Small W Jr, Gaffney DK. NRG Oncology/RTOG 0921: A phase 2 study of postoperative intensity-modulated radiotherapy with concurrent cisplatin and bevacizumab followed by carboplatin and paclitaxel for patients with endometrial cancer. Cancer. 2015 Jul 1;121(13):2156-63. doi: 10.1002/cncr.29337. Epub 2015 Apr 6.

Reference Type: RESULT

PMID: 25847373 (View on PubMed)

Other Identifiers

NCI-2011-01982

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000657979

Identifier Type: -

Identifier Source: secondary_id

RTOG-0921

Identifier Type: -

Identifier Source: secondary_id

RTOG 0921

Identifier Type: OTHER

Identifier Source: secondary_id

RTOG-0921

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA021661

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2011-01982

Identifier Type: -

Identifier Source: org_study_id