Cisplatin and Radiation Therapy With or Without Carboplatin and Paclitaxel in Patients With Locally Advanced Cervical Cancer
A Phase III Trial of Adjuvant Chemotherapy Following Chemoradiation as Primary Treatment for Locally Advanced Cervical Cancer Compared to Chemoradiation Alone: The OUTBACK Trial
This randomized phase III trial studies how well giving cisplatin and radiation therapy
together with or without carboplatin and paclitaxel works in treating patients with locally
advanced cervical cancer. 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. External radiation therapy uses high-energy x rays
to kill tumor cells. Internal radiation uses radioactive material placed directly into or
near a tumor to kill tumor cells. It is not yet known whether giving cisplatin and external
and internal radiation therapy together with carboplatin and paclitaxel kills more tumor
I. To determine if the addition of adjuvant chemotherapy to standard cisplatin-based
chemoradiation improves overall survival.
I. To determine the progression-free survival rates. II. To determine acute and long-term
toxicities. III. To determine patterns of disease recurrence. IV. To determine the
association between radiation protocol compliance and outcomes.
V. To determine patient quality of life, including psycho-sexual health.
I. To determine the association between the results of a follow-up positron emission
tomography (PET) scan performed 4-6 months post completion of chemoradiation and outcomes
for all patients in the trial.
II. To determine the biological predictors of patients' outcomes based on translational
laboratory studies of blood and tissue specimens.
OUTLINE: This is a multicenter study. Patients are stratified according to pelvic or common
iliac nodal involvement (yes vs no), requirement for extended-field radiotherapy treatment
(yes vs no), International Federation of Gynecology and Obstetrics (FIGO) stage (IB/IIA vs
IIB vs IIIB/IVA), age (< 60 years of age vs >= 60 years of age), and hospital/site. Patients
are randomized to 1 of 2 treatment arms.
ARM I: Patients receive cisplatin intravenously (IV) over 60-90 minutes on days 1, 8, 15,
22, and 29. Patients also undergo external-beam radiation therapy once daily, 5 days a week,
for approximately 5 weeks. Patients then undergo high-dose rate, pulsed-dose rate, or
low-dose rate intracavitary brachytherapy.
ARM II: Patients receive cisplatin and undergo external-beam radiation and brachytherapy as
in arm I. Beginning 4 weeks later, patients also receive adjuvant chemotherapy comprising
paclitaxel IV over 3 hours and carboplatin IV over 1 hour on day 1. Treatment repeats every
21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Patients may undergo baseline tumor biopsy and blood collection for future correlative
Patients complete the European Organization for Research and Treatment of Cancer (EORTC)
Core questionnaire (QLQ-C30), the EORTC cervix cancer module (CX24), the ovarian cancer
module (OV28), and the Sexual function-Vaginal Changes Questionnaire (SVQ) questionnaires at
baseline, during, and after completion of study treatment.
After completion of study therapy, patients are followed up every 3 months for 2 years and
then every 6 months for 3 years.
- Eligible patients will have locally advanced cervical cancer suitable for primary
treatment with chemoradiation with curative intent, in addition to:
- Histological diagnosis of squamous cell carcinoma, adenocarcinoma, or
adenosquamous cell carcinoma of the cervix
- FIGO 2008 stage IB1 & node positive, IB2, II, IIIB, or IVA disease
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Histological diagnosis of squamous cell carcinoma, adenocarcinoma or adenosquamous
cell carcinoma of the cervix
- White blood cells (WBC) >= 3.0 x 10^9/L
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
- Platelet count >= 100 x 10^9/L
- Bilirubin =< 1.5 times upper limit of normal (ULN)
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 x ULN
- Creatinine =< ULN (Common Toxicity Criteria [CTC] Grade 0) OR calculated creatinine
clearance (Cockcroft-Gault Formula) >= 60 mL/min OR >= 50 mL/min by
ethylenediaminetetraacetic acid (EDTA) creatinine clearance
- Written informed consent
- Any previous pelvic radiotherapy
- Para-aortic nodal involvement above the level of the common iliac nodes or L3/L4 (if
biopsy proven, PET positive, or >= 15 mm short-axis diameter on computed tomography
- FIGO 2008 stage IIIA disease
- Patients assessed at presentation as requiring interstitial brachytherapy treatment
- Patients with bilateral hydronephrosis unless at least one side has been stented and
renal function fulfills the required inclusion criteria
- Previous chemotherapy for this tumor
- Evidence of distant metastases
- Prior diagnosis of Crohn disease or ulcerative colitis
- Peripheral neuropathy >= grade 2 (per Common Terminology Criteria for Adverse Events
[CTCAE] v. 4)
- Patients who have undergone a previous hysterectomy or will have a hysterectomy as
part of their initial cervical cancer therapy
- Patients with other invasive malignancies, with the exception of non-melanoma skin
cancer and in situ melanoma, who had (or have) any evidence of the other cancer
present within the last 5 years
- Patients who are pregnant or lactating
- Any contraindication to the use of cisplatin, carboplatin, or paclitaxel chemotherapy
- Serious illness or medical condition that precludes the safe administration of the
trial treatment including, but not limited to, ongoing or active infection,
symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia,
or psychiatric illness/social situations that would limit compliance with study
- Human immunodeficiency virus (HIV) positive