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A Phase II Study of Bevacizumab in Combination With Definitive Radiotherapy and Cisplatin Chemotherapy in Untreated Patients With Locally Advanced Cervical Carcinoma


Phase 2
N/A
N/A
Open (Enrolling)
Female
Cervical Adenocarcinoma, Cervical Adenosquamous Cell Carcinoma, Cervical Squamous Cell Carcinoma, Stage IB Cervical Cancer, Stage IIA Cervical Cancer, Stage IIB Cervical Cancer, Stage III Cervical Cancer

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Trial Information

A Phase II Study of Bevacizumab in Combination With Definitive Radiotherapy and Cisplatin Chemotherapy in Untreated Patients With Locally Advanced Cervical Carcinoma


PRIMARY OBJECTIVES:

I. Determine treatment-related serious adverse-event rates and adverse-event rates within
the first 90 days from treatment start in patients with previously untreated locally
advanced carcinoma of the cervix treated with bevacizumab, cisplatin, and concurrent pelvic
radiotherapy.

SECONDARY OBJECTIVES:

I. Evaluate treatment-related serious adverse events and adverse events at any time.

II. Evaluate disease-free survival (local, regional, or distant failure, or death due to any
cause).

III. Evaluate overall survival (death due to any cause).

IV. To collect tissue to perform future immunohistochemical analyses for angiogenic markers
to correlate with clinical outcome; to collect tissue to perform future microarray testing
for evaluation of gene expression.

V. To collect urine and serum for future cytokine analysis.

VI. To implement the image-based brachytherapy guidelines proposed by the Transatlantic
Image-guided Brachytherapy Working Group and collect CT or MRI-based dosimetry of
brachytherapy applications used during the course of treatment for later analysis of
feasibility and consistency as well as dose/volume assessments of tumor control and
complications

OUTLINE: This is a multicenter study.

Patients undergo pelvic external-beam radiotherapy (EBRT) once daily, 5 days a week, for 5
weeks for a total of 45 Gy.

Some patients also undergo low-dose rate brachytherapy twice, 1-3 weeks apart, beginning >=
4 weeks after initiating EBRT or high-dose rate brachytherapy 5 times, >= 48 hours apart,
beginning >= 2 weeks after initiating EBRT. EBRT and chemotherapy are halted on the day of
high-dose rate brachytherapy. Patients receive bevacizumab IV over 30-90 minutes on days 1,
15, and 29 and cisplatin IV over 60 minutes on days 1, 8, 15, 22, 29, and 35.

After completion of study treatment, patients are followed periodically.


Inclusion Criteria:



- Histologically confirmed squamous cell, adenocarcinoma, or adenosquamous cell
carcinoma of the uterine cervix, meeting 1 of the following stage criteria:

- Stage IIB-IIIB

- Stage IB-IIA disease with biopsy-proven pelvic node metastases and/or tumor size
>= 5 cm

- No positive para-aortic lymph nodes

- Zubrod performance status 0-2

- WBC >= 3,000/mm^3

- Absolute granulocyte count >= 1,500/mm^3

- Platelet count >= 100,000/mm^3

- INR < 1.5

- Total bilirubin =< 1.5 mg/dL

- Serum creatinine =< 1.5 mg/dL

- AST and ALT =< 2.5 times upper limit of normal (ULN)

- Serum calcium =< 1.3 times ULN

- Hemoglobin >= 10 g/dL (transfusion allowed)

- Urine protein:creatinine ratio ≤ 0.5 OR urine protein < 1,000 mg by 24-hour urine
collection

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- None of the following illnesses or conditions:

- Medical illness preventing the use of full-dose chemotherapy

- Evidence of bleeding diathesis or coagulopathy

- Prior medical or psychiatric illness that would prevent informed consent or
limit survival to < 6 months

- History of aneurysms, cerebrovascular accident, or arteriovenous malformations

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

- Serious, nonhealing wound, ulcer, or current healing fracture

- History of any type of fistula or GI perforation

- Intra-abdominal abscess within the past 6 months

- No prior invasive malignancy (except nonmelanomatous skin cancer) unless disease free
for >= 3 years

- No significant traumatic injury within the past 28 days

- No clinically significant cardiovascular disease, such as the following:

- Uncontrolled hypertension (blood pressure > 160/90 mm Hg on medication)

- Myocardial infarction within the past 12 months

- Unstable angina within the past 12 months

- New York Heart Association class II-IV congestive heart failure

- Unstable symptomatic arrhythmia requiring medication (i.e., chronic atrial
arrhythmia, atrial fibrillation, or paroxysmal supraventricular tachycardia)

- Arterial thromboembolic events, including transient ischemic attack or
clinically significant peripheral artery disease, within the past 6 months

- Arterial thromboembolic events, including transient ischemic attack or clinically
significant peripheral artery disease, within the past 6 months

- No known hypersensitivity to Chinese hamster ovary cell products or other recombinant
human antibodies

- No known HIV

- No prior organ transplant

- No prior surgery for carcinoma of the cervix other than biopsy

- No prior surgical debulking of pelvic or para-aortic nodes

- No prior pelvic radiotherapy, including transvaginal irradiation to control bleeding

- No prior systemic chemotherapy

- No major surgical procedure or open biopsy within the past 28 days or anticipation of
need for major surgical procedure during the course of the study

- No fine needle aspirations or core biopsies within the past 7 days

- No concurrent major surgical procedure

- No concurrent epoetin alfa or Hypericum perforatum (St. John's wort)

- No concurrent intensity-modulated radiotherapy

- No concurrent transvaginal irradiation to control bleeding

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Subjects With Treatment-related Serious Adverse Events (SAEs) and Adverse Events (AEs) as Assessed by CTCAE v. 3.0 Criteria Within the First 90 Days From Treatment Start.

Outcome Description:

Treatment-related SAEs defined as Grade (Gr) >= 4 vaginal bleeding, Gr >=4 thrombotic event, Gr >=3 arterial event, gastrointestinal (GI) bleeding , or bowel/bladder perforation, and any Gr 5 treatment-related AE. Treatment-related AEs defined as all SAEs, Gr 3-4 nausea, vomiting, or diarrhea persisting for >2 weeks depsite medical intervention, Gr 4 neutropenia or leukopenia persisiting for >7 days, febrile neutropenia defined as a temperature >38.5 degree Celsius and granulocytes < 1000/mm3, Grade 3-4 hematologic toxicity with the exception of neutropenia and leukopenia, and Grade 3-4 GI, renal, cardiac, pulmonary, hepatic, or neurologic AEs. Based on a report by Laciano, et al. an SAE rate of 5% and AE rate of 35% were considered tolerable and an SAE rate >=20% and AE rate >=55% excessive. If there were >=6 pts with SAES or >=22 pts with AEs then the treatment would be rejected. This study design provides alpha of 0.05 and power of 90%.

Outcome Time Frame:

From start of treatment to 90 days.

Safety Issue:

Yes

Principal Investigator

Tracey Schefter

Investigator Role:

Principal Investigator

Investigator Affiliation:

American College of Radiology Imaging Network

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-00722

NCT ID:

NCT00369122

Start Date:

August 2006

Completion Date:

Related Keywords:

  • Cervical Adenocarcinoma
  • Cervical Adenosquamous Cell Carcinoma
  • Cervical Squamous Cell Carcinoma
  • Stage IB Cervical Cancer
  • Stage IIA Cervical Cancer
  • Stage IIB Cervical Cancer
  • Stage III Cervical Cancer
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Carcinoma
  • Carcinoma, Squamous Cell
  • Uterine Cervical Neoplasms
  • Carcinoma, Adenosquamous

Name

Location

Roswell Park Cancer InstituteBuffalo, New York  14263
University of Florida Health Science CenterGainesville, Florida  32610-0296
Northwest Community HospitalArlington Heights, Illinois  60005
Newark Beth Israel Medical CenterNewark, New Jersey  07112
Reading Hospital and Medical CenterReading, Pennsylvania  19612-6052
LDS HospitalSalt Lake City, Utah  84143
Boston Medical CenterBoston, Massachusetts  02118
Central Baptist HospitalLexington, Kentucky  40503
American Fork HospitalAmerican Fork, Utah  84003
Logan Regional HospitalLogan, Utah  84321
Cottonwood Hospital Medical CenterMurray, Utah  84107
McKay-Dee Hospital CenterOgden, Utah  84403
Brigham and Women's HospitalBoston, Massachusetts  02115
Paoli Memorial HospitalPaoli, Pennsylvania  19301-1792
Bryn Mawr HospitalBryn Mawr, Pennsylvania  19010
Lawrence Memorial HospitalLawrence, Kansas  66044
Menorah Medical CenterOverland Park, Kansas  66209
Shawnee Mission Medical CenterShawnee Mission, Kansas  66204
North Kansas City HospitalKansas City, Missouri  64116
Research Medical CenterKansas City, Missouri  64132
Saint Luke's East - Lee's SummitLee's Summit, Missouri  64086
Liberty HospitalLiberty, Missouri  64068
Heartland Regional Medical CenterSaint Joseph, Missouri  64506
Clinton Memorial HospitalWilmington, Ohio  45177
Saint James Hospital and Health Centers Comprehensive Cancer InstituteOlympia Fields, Illinois  60461
Providence Medical CenterKansas City, Kansas  66112
Independence Regional Health CenterIndependence, Missouri  64050
Northwestern UniversityChicago, Illinois  60611
University of RochesterRochester, New York  14642
Emory UniversityAtlanta, Georgia  30322
Albert Einstein Medical CenterPhiladelphia, Pennsylvania  19141
Huntsman Cancer Institute/University of UtahSalt Lake City, Utah  84112
UC Davis Comprehensive Cancer CenterSacramento, California  95817
Lankenau HospitalWynnewood, Pennsylvania  19096
M D Anderson Cancer CenterHouston, Texas  77030
Wake Forest University Health SciencesWinston-Salem, North Carolina  27157
John H Stroger Jr Hospital of Cook CountyChicago, Illinois  60612-3785
Radiation Oncology Practice Corporation SouthwestOverland Park, Kansas  66210
Radiation Oncology Practice Corporation - NorthKansas City, Missouri  64154
Saint Luke's Cancer InstituteKansas City, Missouri  64111
Radiation Oncology Practice Corporation SouthKansas City, Missouri  64114
Saint Luke's Hospital of Kansas CityKansas City, Missouri  64111
Saint Joseph Health CenterKansas City, Missouri  64114
Liberty Radiation Oncology ClinicKansas City, Missouri  64116
Truman Medical CenterKansas City, Missouri  64108
Highland HospitalRochester, New York  14620
Samaritan North Health CenterDayton, Ohio  45415
Wright-Patterson Medical CenterWright-Patterson Afb, Ohio  45433-5529
Mainline Health CCOPWynnewood, Pennsylvania  19096
University of Michigan University HospitalAnn Arbor, Michigan  48109
Sandra L Maxwell Cancer CenterCedar City, Utah  84720
Intermountain Medical CenterMurray, Utah  84157
Utah Valley Regional Medical CenterProvo, Utah  84603
Dixie Medical Center Regional Cancer CenterSaint George, Utah  84770
Intermountain Health CareSalt Lake City, Utah  84103
Utah Cancer Specialists-Salt Lake CitySalt Lake City, Utah  84106
Grady Health SystemAtlanta, Georgia  30303
Saint Luke's South HospitalOverland Park, Kansas  66213
Saint Vincent Oncology CenterIndianapolis, Indiana  46260
Emory University Hospital MidtownAtlanta, Georgia  30308
Cape Radiation OncologyCape Girardeau, Missouri  63703
The New York Methodist HospitalBrooklyn, New York  11215