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

Endometrial Adenocarcinoma Clinical Trial

Official title:

A Phase II Study of Postoperative Intensity Modulated Radiation Therapy (IMRT) With Concurrent Cisplatin and Bevacizumab Followed by Carboplatin and Paclitaxel for Patients With Endometrial Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01005329
• Other study ID #: NCI-2011-01982
• Secondary ID: NCI-2011-01982CD
• Status: Completed
• Phase: Phase 2
• First received: October 29, 2009
• Last updated: February 15, 2018
• Start date: November 6, 2009
• Est. completion date: September 22, 2013

Study information

• Verified date: February 2018
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: September 22, 2013
• Est. primary completion date: June 30, 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Carcinoma, Adenosquamous
• Endometrial Adenocarcinoma
• Endometrial Adenosquamous Carcinoma
• Endometrial Clear Cell Adenocarcinoma
• Endometrial Neoplasms
• 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
• Uterine Neoplasms

Intervention

Biological:
• Bevacizumab
Given IV

Drug:
• Carboplatin
Given IV
• Cisplatin
Given IV

Radiation:
• Intensity-Modulated Radiation Therapy
Undergo IMRT

Drug:
• Paclitaxel
Given IV

Locations

Country	Name	City	State
Canada	London Regional Cancer Program	London	Ontario
Canada	McGill University Department of Oncology	Montreal	Quebec
Hong Kong	Pamela Youde Nethersole Eastern Hospital	Chai Wan
United States	Summa Akron City Hospital/Cooper Cancer Center	Akron	Ohio
United States	Saint Vincent Anderson Regional Hospital/Cancer Center	Anderson	Indiana
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	Summa Barberton Hospital	Barberton	Ohio
United States	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	John H Stroger Jr Hospital of Cook County	Chicago	Illinois
United States	Northwestern University	Chicago	Illinois
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Central Maryland Radiation Oncology in Howard County	Columbia	Maryland
United States	Henry Ford Hospital	Detroit	Michigan
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	M D Anderson Cancer Center	Houston	Texas
United States	Saint Vincent Hospital and Health Care Center	Indianapolis	Indiana
United States	Baptist MD Anderson Cancer Center	Jacksonville	Florida
United States	Baptist Medical Center South	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	Integrated Community Oncology Network-Florida Cancer Center Beaches	Jacksonville Beach	Florida
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Elliot Hospital	Manchester	New Hampshire
United States	Froedtert and the Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
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	Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Radiation Therapy Oncology Group	Philadelphia	Pennsylvania
United States	Kansas City NCI Community Oncology Research Program	Prairie Village	Kansas
United States	Integrated Community Oncology Network-Flager Cancer Center	Saint Augustine	Florida
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Flower Hospital	Sylvania	Ohio
United States	John Muir Medical Center-Walnut Creek	Walnut Creek	California
United States	Wheeling Hospital/Schiffler Cancer Center	Wheeling	West Virginia
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Lankenau Medical Center	Wynnewood	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	Radiation Therapy Oncology Group

Countries where clinical trial is conducted

United States,  Canada,  Hong Kong, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Treatment-related, Grade 3+, Non-hematologic Adverse Events Occuring Within 90 Days After Treatment Start	Adverse events are graded using CTCAE v4.0. Grade refers to the severity of the AE, assigning Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.	From start of treatment to 90 days
Secondary	Percentage of Participants With Treatment-related, Grade 3+, Non-hematologic Adverse Events Occuring Within 1 Year After Treatment Start	Adverse events are graded using CTCAE v4.0. Grade refers to the severity of the AE, assigning Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE. Adverse events reported as definitely, probably, or possibly related to study treatment.	From start of treatment to one year
Secondary	Treatment-related Grade 3+ Adverse Events	The highest grade adverse event per patient reported as definitely, probably, or possibly related to study treatment is counted. Adverse events are graded using CTCAE v4.0. Grade refers to the severity of the AE, assigning Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.	From start of treatment to end of follow-up, up to 43.4 months; analysis occurred after all patients had been on study for at least one year.
Secondary	Overall Survival (Two-year Rate Reported)	Failure was defined as death due to any cause. Patients alive at time of analysis were censored at the date of last contact. Survival rate at two years was estimated using the Kaplan-Meier method.	From registration to two years
Secondary	Disease-free Survival (Two-year Rate Reported)	Failure was defined as pelvic failure (recurrence in the pelvis, which must be confirmed by histologic or cytologic biopsy of the recurrent lesion), distant failure (confirmed by histologic or cytologic biopsy of the recurrent lesion), or death due to any cause. Patients alive at time of analysis were censored at the date of last contact. Disease-free survival rate at two years was estimated using the Kaplan-Meier method.	From registration to two years
Secondary	Pelvic Failure Rate (Two-year Rate Reported)	Pelvic failure (PF) was defined as disease recurrence in the pelvis, including the pelvic or sacral lymph nodes, and required confirmation by histologic or cytologic biopsy of the recurrent lesion. Death was considered a competing risk. PF rates were estimated using the cumulative incidence method.	From registration to two years
Secondary	Distant Failure (Two-year Rate Reported)	Distant Failure (DF) was defined as the appearance of distant metastasis. Death was considered a competing risk. DF rates were estimated using the cumulative incidence method.	From registration to two years