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Randomized Phase III Clinical Trial of Weekly Versus Tri-weekly Cisplatin Based Chemoradiation in Locally Advanced Cervical Cancer

Phase 3
18 Years
75 Years
Open (Enrolling)
Cervical Cancer

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Trial Information

Randomized Phase III Clinical Trial of Weekly Versus Tri-weekly Cisplatin Based Chemoradiation in Locally Advanced Cervical Cancer

Cervical carcinoma is one of the most common gynecologic cancers worldwide. The prognosis of
cervical cancer is favorable, with around 80-90% 5-year survival rate in early stage
disease. However, advanced disease carries a poor prognosis. Current standard treatment for
locally advanced cervical cancer, which is not eligible for surgical treatment, is
cisplatin-based concurrent chemoradiation (CRT). Based on the results of five randomized
clinical trials, which consistently showed improved survival in patients treated with
cisplatin-based CRT, the National Cancer Institute (NCI) of the United States announced that
'Strong consideration should be given to the incorporation of concurrent cisplatin-based
chemotherapy with RT in women who require radiation therapy for treatment of cervical
cancer' in 1999.

Although recently reported meta-analysis studies also demonstrated improved local control
rates and survival with cisplatin-based chemotherapy concurrent to radiation therapy (RT),
the optimal cisplatin dose and dosing schedule are still undetermined. Among the previous
five randomized clinical trials, two trials performed by the Gynecologic Oncology Group
(GOG) used weekly cisplatin 40 mg/m2 while the other three trials used tri-weekly cisplatin
at a dosage range of 50 mg/m2 to 75 mg/m2 combined with 5-fluorouracil (5-FU). Despite the
diversity in cisplatin dose and dosing schedules, weekly cisplatin at a dose of 40 mg/m2
concurrent to RT is widely accepted as the standard regimen of CRT because of its
convenience, equal effectiveness, and favorable toxicity in comparison to other 5-FU
combined regimens.

However, as a result of the GOG 165 study, which was closed prematurely because an interim
analysis found that patients in the 5-FU treatment group were not likely to achieve a better
outcome, the role of 5-FU (previously popularly included in clinical trials) as a
radiosensitizer became subject to debate. Furthermore, a clinical trial performed by the NCI
in Canada comparing pelvic RT alone with weekly cisplatin 40 mg/m2 concurrent to RT failed
to show improvement of progression free and 5-year survival. While the authors suggested
several possible reasons for why their study failed to demonstrate a survival benefit with
concurrent weekly cisplatin 40 mg/m2 chemotherapy, other investigators have tried to find
another optimal dose and dosing schedule for cisplatin administration.

In light of the results of the previous clinical trial that indicated 5-FU may not be an
active radiosensitizer, weekly cisplatin 40 mg/m2 and tri-weekly cisplatin 75 mg/m2 remain
the most popular cisplatin doses and dosing schedules. However, despite the possible
advantages of tri-weekly cisplatin 75 mg/m2, which offer an increased peak concentration of
cisplatin and cisplatin administration during brachytherapy, no clinical trials thus far
have directly compared weekly and tri-weekly cisplatin-based chemotherapy concurrent to RT.

Recently the investigators reported a randomized phase II trial to compare the compliance to
and toxicity of weekly cisplatin 40 mg/m2 and tri-weekly cisplatin 75 mg/m2 administration
concurrent to RT. The study showed that tri-weekly cisplatin 75 mg/m2 concurrent to RT is
feasible and increase 5-year survival rate significantly compared to weekly cisplatin 40
mg/m2 in patients with locally advanced cervical cancer (66.5% in the weekly arm, 88.7% in
the tri-weekly arm; HR=0.375, 95% CI: 0.154-0.914, p= .03).

Therefore, in this randomized phase III trial, The investigators intend to confirm the
survival difference between weekly cisplatin 40 mg/m2 and tri-weekly cisplatin 75 mg/m2
administration concurrent to RT in this patient population.

Inclusion Criteria:

- Eligible patients will have pathologically proven primary locally advanced cervical
cancer with squamous cell carcinoma, adenosquamous carcinoma or adenocarcinoma
histology suitable for primary treatment with chemoradiation with curative intent

- FIGO 2008 stage 1B2, 2B, 3B, 4A

- Age 18 years or older

- Eastern Cooperative Oncology Group (ECOG) performance status 0-2

- Patients must have adequate Hematologic function(ANC ≥ 1,500/mcl and platelets ≥
100,000/mcl), Renal function(serum creatinine ≤ ULN or calculated creatinine
clearance ≥ 60 mL/min), Hepatic function(serum bilirubin ≤ 1.5 x ULN and AST ≤ 2.5 x
ULN and ALT≤ 2.5 x ULN)

- Patients must have signed an approved informed consent

Exclusion Criteria:

- Patients with cervix cancer who have received any previous radiation or chemotherapy

- Patients assessed at presentation as requiring interstitial brachytherapy treatment

- FIGO stage 3A disease

- Para-aortic nodal involvement above the level of the common iliac nodes or L3/L4 (if
biopsy proven, PET positive or > 15mm short axis diameter on CT)

- Patients with bilateral hydronephrosis unless at least one side has been stented and
renal function fulfils the required inclusion criteria

- Previous chemotherapy for this tumor

- Evidence of distant metastases

- Prior diagnosis of Crohn's disease or ulcerative colitis

- Patients who are pregnant or lactating

- History of 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

- 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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall survival

Outcome Description:

Observed length of life from entry into the study to death; or for living patients, the date of last contact regardless of whether or not this contact is on a subsequent protocol.

Outcome Time Frame:

From entry into the study to 5 year after treatment or death

Safety Issue:


Principal Investigator


Investigator Role:

Principal Investigator

Investigator Affiliation:



Korea: Institutional Review Board

Study ID:

KGOG 1027/THAI 2012



Start Date:

March 2012

Completion Date:

March 2020

Related Keywords:

  • Cervical Cancer
  • Cervical cancer
  • Concurrent chemoradiation
  • Cisplatin
  • Uterine Cervical Neoplasms