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A Phase II Study of Paclitaxel and Carboplatin in Patients With Intermediate-Risk Adenocarcinoma of the Endometrium

Phase 2
19 Years
Not Enrolling
Uterine Cancer

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Trial Information

A Phase II Study of Paclitaxel and Carboplatin in Patients With Intermediate-Risk Adenocarcinoma of the Endometrium

Endometrial cancer is the most common gynecologic malignancy in the United States with
40,880 new cases diagnosed and 7,310 deaths attributable to this malignancy expected in
2005. The majority of patients diagnosed with endometrial cancer have early stage disease
that is amenable to treatment with hysterectomy and bilateral salpingo-oophorectomy with
excellent clinical outcomes. Surgical staging has improved accuracy over clinical staging
for defining a low-risk population of patients who have favorable long-term outcomes with
surgery alone. However, approximately 10-15% of patients with surgical stage I endometrial
carcinoma (confined to the uterus) will have invasion to the outer one-half of the
myometrium (stage IC) and a moderately to poorly differentiated tumor (grade 2 or 3). These
patients are at a higher risk for recurrence (approximately 20-25% recurrence rate over 5
years). This patient population has been historically considered at "intermediate-risk" for
recurrence because they are at lower risk than patient with disease spread beyond the
uterus, but higher risk than patients with a grade 1 tumor or minimally invasive (Stage IA
or IB). The optimal mode of postoperative management for this population of patients has
yet to be defined.

Historically, radiation therapy has been used in some form in patients diagnosed with
intermediate-risk endometrial cancer. Two randomized trials published in the last 5 years
have evaluated the use of adjuvant radiation therapy in patients with intermediate-risk
endometrial adenocarcinoma. the Gynecologic Oncology Group (GOG) studied the use of
adjuvant whole pelvic radiation (WPRT) versus no adjuvant therapy (NAT) in patients with
stage IB, IC, and II (occult)endometrial adenocarcinoma. In a study of 392 patients, the
use of WPRT had a substantial impact on local recurrences (18 in NAT versus 3 in WPRT), but
had no impact on the risk of distant recurrence (18 NAT versus 11 in WPRT). Because of the
lack of distant control, the use of WPRT did not impact overall survival (estimated 4 year
survival 86% in NAT versus 92% in WPRT, p=0.557). The PORTEC trial randomized patients with
intermediate-risk Stage I endometrial carcinoma to WPRT versus NAT. Of note, patients in
this trial were not surgically staged. Of 714 patients with a median follow-up of 52
months,local recurrence rates were 4% in the WPRT group versus 14% in the control group
(p<0.001). The use of WPRT did not impact 5-year overall survival (81% WPRT versus 85%
NAT). Furthermore, some clinicians have advocated observation after surgical staging with
radiation therapy reserved for those patients who recur locally. Several reports have
reported salvage rates of 50-66% for patients with local recurrences. Given that
approximately 20-25% patients in this population will recur locally, many clinicians prefer
to use local radiation therapy as salvage therapy, thus sparing the majority of patients the
potential long-term effects of pelvic radiation therapy. Given that radiation therapy does
not affect distant metastasis and carries significant long-term morbidity, other therapies
are necessary to improve disease-free survival in this setting. Adjuvant systemic
chemotherapy is one potential option for these patients since it may sterilize both local
and distant metastases. The use of adjuvant chemotherapy may be more desirable than
radiation therapy because most side effects of chemotherapy are short-term and subside once
therapy is completed or discontinued.

Multiple chemotherapeutic agents including cisplatin, doxorubicin HCL, paclitaxel,
carboplatin, and oral etoposide have been studied for patients with advanced or recurrent
endometrial cancer. A phase III study by the Gynecologic Oncology Group (GOG) compared
doxorubicin with and without cisplatin (GOG 107) for patients with advanced or recurrent
endometrial cancer. A higher response rate (42% vs. 25%) was noted for combination therapy
and has been considered by many to be the standard chemotherapy regimen for treatment of
patients with advanced endometrial cancer. Paclitaxel has also been studied as a single
agent and in combination with platinum compounds in this setting. A phase II study that
combined paclitaxel 175 mg/m2 as a 3-hour infusion with cisplatin 75 mg/m2 reported a 67%
response rate. There were seven complete responses and nine partial responses with an
18-month median overall survival. An additional phase II study evaluated the efficacy of
combining paclitaxel and carboplatin in both primary and recurrent non-papillary and
papillary tumors following radiation therapy. the response rate was 78% in patients with
primary advanced non-papillary tumors with a median disease-free survival of 23 months, with
the median overall survival of 15 months. Currently, many clinicians are using a combination
of paclitaxel, doxorubicin, and cisplatin (TAP), based on a phase III GOG study that
demonstrated not only a significantly higher response rate (57% vs. 33%) over the
combination of doxorubicin and cisplatin (AP), but also a survival advantage (median, 15.3
vs. 12.3 months; P=.037). Significantly more neurotoxicity was experienced by patients in
the TAP arm. Currently, the GOG is evaluating the TAP combination versus the more tolerable
regimen of paclitaxel and carboplatin in a phase III setting.

The combination of paclitaxel and carboplatin is considered the standard of care for both
high-risk early stage ovarian cancer and advanced ovarian cancer. The safety of this
combination is well established in a number of phase III trials and currently is used in the
primary setting for patients with ovarian cancer and advanced endometrial cancer. Although
this combination is considered active in endometrial carcinoma, there is a paucity of data
regarding the use of adjuvant chemotherapy in the setting of intermediate-risk endometrial
adenocarcinoma. Accordingly, this phase II study will evaluate the combination of
paclitaxel and carboplatin as adjuvant therapy for patients with early stage adenocarcinoma
of the endometrium at elevated-risk for recurrence.

Inclusion Criteria:

- Patients must have a elevated risk, surgical stage II, stage IC, grade 2 or 3
adenocarcinoma of the endometrium.

- Patients must have undergone, a total abdominal hysterectomy, bilateral
salpingo-oophorectomy, peritoneal washings, and a pelvic and para-aortic

- Patients must have adequate organ function defined as:

1. Platelets >/= 100,000/µ

2. Granulocytes (ANC)>/= 1,500/µl

3. Creatinine
5. Bilirubin within institutional normal limits

- Patients must have adequate performance status (ECOG performance status 0-2 or
Karnofsky Performance Status >40)

- Patients must be age 19 or greater and have signed informed consent.

Exclusion Criteria:

- Patients with history of other malignancies within 5 years (except non- melanoma skin
cancer or carcinoma-in-situ of the cervix) are ineligible.

- Patients with high-risk histologic subtypes of endometrial cancer such as papillary
serous or clear cell histology are ineligible.

- Patients with histologic evidence of uterine sarcoma, including leiomyosarcoma,
carcinosarcoma, endometrial stromal sarcoma, and adenosarcoma are ineligible.

- Patients who have received past pelvic radiotherapy are ineligible.

- Patients receiving any other investigational agents are ineligible.

- Patients with known hypersensitivity to paclitaxel and/or carboplatin are ineligible.

Type of Study:


Study Design:

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

Outcome Measure:

Disease-free Survival

Outcome Description:

Number of months of survival with no evidence of disease

Outcome Time Frame:

4 years - Median follow up time of 45.3 months

Safety Issue:


Principal Investigator

John M. Straughn, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Assistant Professor, Dept of OB/Gyn, Division of GYN Oncology


United States: Food and Drug Administration

Study ID:

F060328016 (UAB 0604)



Start Date:

March 2006

Completion Date:

September 2011

Related Keywords:

  • Uterine Cancer
  • Uterine Neoplasms



UAB Women's and Infant Center, 1700 6th Avenue South Birmingham, Alabama  35233