Radiation Therapy With or Without Cisplatin in Treating Patients With Recurrent Endometrial Cancer

Study ID
GOG-0238

Cancer Related
Yes

Healthy Volunteers
No

Study Sites

  • Clements University Hospital
  • UT Southwestern Ambulatory Services
  • Zale Lipshy University Hospital
  • Parkland Health & Hospital System

Contact
Annette Paulsen
214/648-2290
annette.paulsen@utsouthwestern.edu

Principal Investigator
David Miller

Official Title

A Randomized Trial of Pelvic Irradiation With or Without Concurrent Weekly Cisplatin in Patients With Pelvic-Only Recurrence of Carcinoma of the Uterine Corpus

Brief Overview


This randomized phase II trial studies radiation therapy and cisplatin to see how well they
work compared with radiation therapy alone in treating patients with endometrial cancer that
has come back. Radiation therapy uses high-energy x-rays and other types of radiation to
kill tumor cells. Drugs used in chemotherapy, such as cisplatin, work in different ways to
stop the growth of tumor cells, either by killing the cells, by stopping them from dividing,
or by stopping them from spreading. It is not yet known whether giving radiation therapy
together with cisplatin is more effective than radiation therapy alone in treating patients
with endometrial cancer.

Summary


PRIMARY OBJECTIVES:

I. To assess whether pelvic radiation therapy with concurrent cisplatin is more promising
with respect to progression-free survival than pelvic radiation therapy alone in the
treatment of recurrent uterine carcinoma limited to the pelvis and vagina.

SECONDARY OBJECTIVES:

I. To capture the sites of recurrence subsequent to treatment with pelvic radiation with or
without concurrent weekly cisplatin in women with recurrent uterine carcinoma.

II. To estimate overall survival of patients with recurrent uterine carcinoma treated with
pelvic radiation therapy with or without concurrent weekly cisplatin.

III. To estimate the prognostic significance of the location (central pelvis versus vagina)
and size of the recurrence, in addition to the prognostic significance in the salvage
setting of the histological subtype, grade, patient age, race, performance status, and the
presence of lymph-vascular space involvement of the original tumor at the time of initial
hysterectomy.

IV. To evaluate toxicity derived from the combined cisplatin and radiation compared with
radiation alone in this patient population.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients undergo external-beam radiotherapy (EBRT) to the pelvis daily on days 1-5
for 5 weeks. After completion of EBRT, patients undergo intracavitary low-dose rate or
high-dose rate brachytherapy* or low-dose rate interstitial brachytherapy*.

ARM II: Patients undergo EBRT as in Arm I and receive cisplatin intravenously (IV) over 1-2
hours on days 1, 8, 15, 22, and 29. Patients then undergo brachytherapy* as in Arm I.

NOTE: *IMRT boost is allowed for patients who are not candidates for brachytherapy. IMRT may
also be used for the entire course of therapy for the treatment of the whole pelvis and/or
the boost in patients not undergoing brachytherapy. In both arms, treatment continues in the
absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and
then every 6 months for 3 years.

Participant Eligibility


Inclusion Criteria:

- All patients must have undergone complete hysterectomy and bilateral
salpingo-oophorectomy at the time of original therapy for their uterine carcinoma

- Patients must have a biopsy with histologically confirmed diagnosis of recurrent
endometrial cancer confined to the pelvis and/or vagina and no evidence of
extrapelvic disease

- Patients must have endometrial carcinoma including endometrioid adenocarcinoma,
adenocarcinoma with squamous differentiation, mucinous adenocarcinoma, squamous cell
carcinoma, mixed carcinoma, undifferentiated carcinoma, clear cell adenocarcinoma,
and serous adenocarcinoma histologies

- Patients must have no evidence of extrapelvic disease; complete workup staging should
be performed prior to initiation of therapy to rule-out presence of metastatic
disease; this should include: computed tomography (CT) scan of the thorax with IV
contrast, as well as a CT of the pelvis and abdomen with IV and oral (PO) contrast
performed using multi-detector CT and equal or less than 5 mm slice thickness; if the
patient is unable to tolerate contrast, then magnetic resonance imaging (MRI) with IV
gadolinium should be performed; a chest x-ray should be done first, and if abnormal,
then a CT scan of the chest should be done

- Primary surgical debulking before protocol therapy is permissible; this would include
removal of gross symptomatic disease in the pelvis and/or vagina

- Exenterative surgery is not permissible; patients with complete resection of
gross recurrent disease are eligible

- Patients may have received prior hormone therapy and/or systemic chemotherapy; such
therapy must have been completed at least 6 months prior to study entry and the
patient has clear evidence of disease subsequent to such therapy; patients must not
have received neoadjuvant chemotherapy for the present recurrent disease

- Patients must have Gynecologic Oncology Group (GOG) performance status 0, 1, or 2

- Patients must have an estimated survival greater or equal to 3 months

- Absolute neutrophil count (ANC) >= 1,500/mm^3 , equivalent to Common Toxicity
Criteria (Common Terminology Criteria for Adverse Events [CTCAE] version [v] 3.0)
grade 1

- Platelets >= 100,000/mm^3, equivalent to CTCAE v 3.0 grade 0-1

- Creatinine =< institutional upper limit normal (ULN), CTCAE v 3.0 grade 0; NOTE: if
creatinine > ULN, creatinine clearance must be > 50 mL/min

- Bilirubin =< 1.5 x ULN (CTCAE v 3.0 grade 1)

- Serum glutamic oxaloacetic transaminase (SGOT) =< 2.5 x ULN (CTCAE v 3.0 grade 0-1)

- Alkaline phosphatase =< 2.5 x ULN (CTCAE v 3.0 grade 0-1)

- Neuropathy (sensory and motor) =< CTCAE v 3.0 grade 1

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

- Patients who have met the pre-entry requirements

- Patients must have signed an approved informed consent and Health Insurance
Portability and Accountability Act (HIPAA) authorization

Exclusion Criteria:

- Patients with evidence of disease outside of the pelvis, including presence of
positive periaortic or inguino-femoral nodes

- Patients who have received previous vaginal, pelvic, or abdominal irradiation

- Patients who received chemotherapy directed at the present recurrence

- Patients with septicemia or severe 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 complete surgical resection of the recurrent tumor and
have no evidence of residual disease evaluable clinically and by CT or MRI imaging,
following resection

- 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 with history of active collagen vascular disease

- Patients with GOG performance grade of 3 or 4