Clinical trial NCT01005329: Intensity-Modulated Radiation Therapy, Cisplatin, and Bevacizumab Followed by Carboplatin and Paclitaxel in Treating Patients Who Have Undergone Surgery for Endometrial Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: Radiation Therapy Oncology Group
First posted: 2009-10-30
Enrollment: 34
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Percentage of Participants With Treatment-related, Grade 3+, Non-hematologic Adverse Events Occuring Within 90 Days After Treatment Start
timeFrame: From start of treatment to 90 days
Secondary outcomes:
measure: Percentage of Participants With Treatment-related, Grade 3+, Non-hematologic Adverse Events Occuring Within 1 Year After Treatment Start
timeFrame: From start of treatment to one year
measure: Treatment-related Grade 3+ Adverse Events
timeFrame: 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.
measure: Overall Survival (Two-year Rate Reported)
timeFrame: From registration to two years
measure: Disease-free Survival (Two-year Rate Reported)
timeFrame: From registration to two years
measure: Pelvic Failure Rate (Two-year Rate Reported)
timeFrame: From registration to two years
measure: Distant Failure (Two-year Rate Reported)
timeFrame: From registration to two years
Other outcomes:
Locations:
city: Berkeley
country: United States
facility: Alta Bates Summit Medical Center-Herrick Campus
state: California
city: Walnut Creek
country: United States
facility: John Muir Medical Center-Walnut Creek
state: California
city: Colorado Springs
country: United States
facility: Penrose-Saint Francis Healthcare
state: Colorado
city: Fort Collins
country: United States
facility: Poudre Valley Hospital
state: Colorado
city: Newark
country: United States
facility: Christiana Care Health System-Christiana Hospital
state: Delaware
city: Jacksonville Beach
country: United States
facility: Integrated Community Oncology Network-Florida Cancer Center Beaches
state: Florida
city: Jacksonville
country: United States
facility: Baptist MD Anderson Cancer Center
state: Florida
city: Jacksonville
country: United States
facility: Integrated Community Oncology Network-Southside Cancer Center
state: Florida
city: Jacksonville
country: United States
facility: University of Florida Health Science Center - Jacksonville
state: Florida
city: Jacksonville
country: United States
facility: Baptist Medical Center South
state: Florida
city: Orange Park
country: United States
facility: 21st Century Oncology-Orange Park
state: Florida
city: Palatka
country: United States
facility: 21st Century Oncology-Palatka
state: Florida
city: Panama City
country: United States
facility: Bay Medical Center
state: Florida
city: Saint Augustine
country: United States
facility: Integrated Community Oncology Network-Flager Cancer Center
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: John H Stroger Jr Hospital of Cook County
state: Illinois
city: Anderson
country: United States
facility: Saint Vincent Anderson Regional Hospital/Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: Saint Vincent Hospital and Health Care Center
state: Indiana
city: Prairie Village
country: United States
facility: Kansas City NCI Community Oncology Research Program
state: Kansas
city: Baltimore
country: United States
facility: University of Maryland/Greenebaum Cancer Center
state: Maryland
city: Columbia
country: United States
facility: Central Maryland Radiation Oncology in Howard County
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Manchester
country: United States
facility: Elliot Hospital
state: New Hampshire
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Akron
country: United States
facility: Summa Akron City Hospital/Cooper Cancer Center
state: Ohio
city: Barberton
country: United States
facility: Summa Barberton Hospital
state: Ohio
city: Sylvania
country: United States
facility: Flower Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Paoli
country: United States
facility: Paoli Memorial Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Radiation Therapy Oncology Group
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Medical Center
state: Pennsylvania
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute/University of Utah
state: Utah
city: Wheeling
country: United States
facility: Wheeling Hospital/Schiffler Cancer Center
state: West Virginia
city: Milwaukee
country: United States
facility: Froedtert and the Medical College of Wisconsin
state: Wisconsin
city: London
country: Canada
facility: London Regional Cancer Program
state: Ontario
city: Montreal
country: Canada
facility: McGill University Department of Oncology
state: Quebec
city: Chai Wan
country: Hong Kong
facility: Pamela Youde Nethersole Eastern Hospital
Study officials:
affiliation: Radiation Therapy Oncology Group
name: Akila Viswanathan
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.