Cisplatin and Radiation Therapy Followed by Paclitaxel and Carboplatin in Treating Patients With Stage IB-IVA Cervical Cancer

PRIMARY OBJECTIVES:

I. To determine the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLT) of
adjuvant carboplatin and paclitaxel chemotherapy following concurrent weekly cisplatin
chemotherapy and extended field radiation in women with newly diagnosed stage IB-IVA cervical
cancer, with positive para-aortic nodes.

II. To determine the feasibility of the treatment regimen over the four cycles of adjuvant
chemotherapy once the MTD is estimated.

III. To assess the toxicities of the treatment regimen the National Cancer Institute (NCI)
Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

SECONDARY OBJECTIVES:

I. To assess the response rate to this treatment regimen in patients with measurable disease.

II. To examine progression-free survival for one year on this treatment regimen.

III. To examine overall survival. IV. To examine the location of recurrence, loco-regional
versus distant for one year after completion of therapy.

V. To estimate the frequency of chronic toxicities experienced within one year of study
entry.

OUTLINE: This is a dose-escalation study of carboplatin and paclitaxel.

Patients receive cisplatin intravenously (IV) over 1 hour on days 1, 8, 15, 22, 29, and 36
and undergo extended-field radiotherapy daily 5 days a week for 6 weeks followed by
brachytherapy. Beginning 4-6 weeks after completion of chemoradiation, patients receive
adjuvant chemotherapy comprising paclitaxel IV over 3 hours and carboplatin IV over 30-60
minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease
progression or unacceptable toxicity.

After completion of study therapy, patients are followed up every 3 months for 1 year.

Inclusion Criteria:

- Patients with histologically confirmed cervical cancer (squamous, adenocarcinoma, or
adenosquamous): International Federation of Gynecology and Obstetrics (FIGO) clinical
stages IB, IIA, IIB, IIIA, IIIB, IVA, with positive para-aortic lymph nodes confirmed
by positron emission tomography (PET)/computed tomography (CT) scan, fine needle
biopsy, extraperitoneal biopsy, laparoscopic biopsy or lymphadenectomy

- Patients must have a Gynecologic Oncology Group (GOG) performance status of 0-2

- Absolute neutrophil count (ANC) >= 1,500/mcl

- Platelets >= 100,000/mcl

- Creatinine =< institutional upper limit normal (ULN); Note: if creatinine > ULN,
creatinine clearance must be > 50 mL/min

- Bilirubin =< 1.5 times ULN

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and
alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x
ULN

- Alkaline phosphatase =< 2.5 x ULN

- Neuropathy (sensory and motor) =< grade 1

- Patients with ureteral obstruction must undergo stent or nephrostomy tube placement
prior to study entry

- Patients must meet the pre-entry requirements

- Patients must have signed an approved informed consent and authorization permitting
the release of personal health information

- Patients of child-bearing potential must have a negative serum pregnancy test prior to
study entry (within 72 hours prior to initiation of study treatment) and be practicing
an effective form of contraception; women should not breast-feed while on this study

- Patients must not be receiving any other investigational agent

- Patients should have an audiogram at baseline, and patients with pre-existing hearing
loss or hearing loss during treatment should be assessed frequently during cisplatin
therapy

Exclusion Criteria:

- Patients who have received previous pelvic or abdominal radiation, cytotoxic
chemotherapy, or previous therapy of any kind for this malignancy

- Patients with active infection

- Patients who have circumstances that will not permit completion of this study or the
required follow-up

- Patients with renal abnormalities, such as pelvic kidney, horseshoe kidney, or renal
transplantation, that would require modification of radiation fields

- Patients with a history of other invasive malignancies, with the exception of
non-melanoma skin cancer, are excluded if there is any evidence of other malignancy
being present within the last five years; patients are also excluded if their previous
cancer treatment contraindicates this protocol therapy

- Patients who have undergone major surgery, excluding diagnostic biopsy, within 30 days
(to allow for full recovery) prior to registration

- Patients who have a significant history of cardiac disease, (i.e., uncontrolled
hypertension, unstable angina, congestive heart failure, or uncontrolled arrhythmias)
within 6 months of registration

- Patients who have a known sensitivity reactions to products containing Cremophor EL