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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


Phase 2
18 Years
N/A
Not Enrolling
Female
Endometrial Adenocarcinoma, Endometrial Adenosquamous Cell Carcinoma, Endometrial Clear Cell Carcinoma, Endometrial Papillary Serous Carcinoma, Stage I Endometrial Carcinoma, Stage II Endometrial Carcinoma, Stage III Endometrial Carcinoma, Stage IV Endometrial Carcinoma

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Trial Information

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


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: This is a multicenter study.

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 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.


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 CT scan or
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

- 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)

- AST and 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

- INR < 1.5 (for patients treated with warfarin within the past 14 days)

- Not nursing

- No neuropathy ≥ CTCAE grade 1

- No ototoxicity > CTCAE grade 2

- No serious, active comorbidity, including any of the following:

- Unstable angina and/or 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

- AIDS based upon current CDC definition (HIV testing is not required)

- Active gastrointestinal (GI) ulcers, GI bleeding, inflammatory bowel disease, or
GI obstruction

- Inadequately controlled hypertension, defined as systolic 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-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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Treatment-related, grade 3+, non-hematologic adverse events as assessed by NCI CTCAE v4.0

Outcome Time Frame:

Up to 90 days

Safety Issue:

Yes

Principal Investigator

Akila Viswanathan

Investigator Role:

Principal Investigator

Investigator Affiliation:

American College of Radiology Imaging Network

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2011-01982

NCT ID:

NCT01005329

Start Date:

November 2009

Completion Date:

Related Keywords:

  • Endometrial Adenocarcinoma
  • Endometrial Adenosquamous Cell Carcinoma
  • Endometrial Clear Cell Carcinoma
  • Endometrial Papillary Serous Carcinoma
  • Stage I Endometrial Carcinoma
  • Stage II Endometrial Carcinoma
  • Stage III Endometrial Carcinoma
  • Stage IV Endometrial Carcinoma
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Carcinoma
  • Endometrial Neoplasms
  • Carcinoma, Adenosquamous
  • Adenocarcinoma, Clear Cell
  • Adenomyoepithelioma
  • Cystadenocarcinoma, Serous
  • Adenoma

Name

Location

Akron City Hospital Akron, Ohio  44304
West Michigan Cancer Center Kalamazoo, Michigan  49007-3731
Henry Ford Hospital Detroit, Michigan  48202
University of Florida Health Science Center Gainesville, Florida  32610-0296
Bay Medical Center Panama City, Florida  32401
University of Oklahoma Health Sciences Center Oklahoma City, Oklahoma  73104
John Muir Medical Center Walnut Creek, California  94598
Brigham and Women's Hospital Boston, Massachusetts  02115
Paoli Memorial Hospital Paoli, Pennsylvania  19301-1792
Poudre Valley Radiation Oncology Fort Collins, Colorado  80528
Northwestern University Chicago, Illinois  60611
Flower Hospital Sylvania, Ohio  43560-2197
Huntsman Cancer Institute/University of Utah Salt Lake City, Utah  84112
Lankenau Hospital Wynnewood, Pennsylvania  19096
M D Anderson Cancer Center Houston, Texas  77030
Froedtert and the Medical College of Wisconsin Milwaukee, Wisconsin  53226
Wake Forest University Health Sciences Winston-Salem, North Carolina  27157
Penrose-Saint Francis Healthcare Colorado Springs, Colorado  80907
Edna Williams Cancer Center at the Baptist Cancer Institute Jacksonville, Florida  32207
Elliot Hospital Manchester, New Hampshire  03103
Summa Barberton Hospital Barberton, Ohio  44203
Wheeling Hospital Wheeling, West Virginia  26003
University of Maryland Greenebaum Cancer Center Baltimore, Maryland  21201
Stony Brook University Medical Center Stony Brook, New York  11794
Saint John's Health System Cancer Center Anderson, Indiana  46016
Saint Vincent Oncology Center Indianapolis, Indiana  46260
Alta Bates Summit Medical Center-Herrick Campus Berkeley, California  94704
Christiana Care Health System-Christiana Hospital Newark, Delaware  19718
Cancer Specialists of North Florida-Southside Jacksonville, Florida  32207
Cancer Specialists of North Florida-Beaches Jacksonville Beach, Florida  32250
Cancer Specialists of North Florida-Baptist South Jascksonville, Florida  32258
Cancer Specialists of North Florida-Orange Park Orange Park, Florida  32073
Cancer Specialists of North Florida-Putnam Palatka, Florida  32177
Cancer Specialists of North Florida-Saint Augustine Saint Augustine, Florida  32086
Central Maryland Radiation Oncology in Howard County Columbia, Maryland  21044