Tri-weekly Cisplatin Based Chemoradiation in Locally Advanced Cervical Cancer
NCT ID: NCT01561586
Last Updated: 2019-02-27
Study Results
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Basic Information
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UNKNOWN
PHASE3
374 participants
INTERVENTIONAL
2012-03-31
2023-03-31
Brief Summary
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In light of the results of the previous clinical trial, weekly cisplatin 40 mg/m2 considered to be a standard regiment in cisplatin doses and dosing schedules. However, our randomized phase II trial showed that tri-weekly cisplatin 75mg/m2 has lower toxicities and a better outcome in locally advanced cervical cancer.
In this randomized phase III trial, the investigators investigate that there may be a survival difference between weekly cisplatin 40 mg/m2 and tri-weekly cisplatin 75 mg/m2 administration concurrent to RT in cervical cancer.
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Detailed Description
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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.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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A: Weekly cisplatin with RT
Weekly cisplatin 40mg/m2 six cycles concurrent to radiation therapy
Weekly cisplatin with RT
Cisplatin 40mg/m2 IV Weekly For 6 Cycles.(The 6th cycle of cisplatin may be omitted if external beam radiation therapy has been completed) Cisplatin may be diluted and administered per established institutional guidelines. For general suggestion, 40 mg/ m2 of cisplatin may be diluted in 250 ml 0.9% sodium chloride and administered over one or two hours.
Cisplatin will be given on the first day of external RT (Day 1), preferably, and must be given prior to radiation treatment on that day
External beam RT will be followed by intracavitary brachytherapy. The total elapsed time for completion of external beam to the whole pelvis, intracavitary BT, and parametrial / nodal RT shall not exceed eight weeks (56 days)
B: Tri-weekly cisplatin with RT
Tri-weekly cisplatin 75mg/m2 three cycles concurrent to radiation therapy
Tri-weekly cisplatin with RT
Tri-weekly cisplatin 75mg/m2 three cycles concurrent to radiation therapy
Cisplatin may be diluted and administered per established institutional guidelines. For general suggestion, 75 mg/m2 of cisplatin may be diluted in 500 ml 0.9% sodium chloride and administered over one or two hours (rate of 1 mg of cisplatin per minute).
Cisplatin will be given on the first day of external RT (Day 1), preferably, and must be given prior to radiation treatment on that day.
External beam RT will be followed by intracavitary brachytherapy. The total elapsed time for completion of external beam to the whole pelvis, intracavitary BT, and parametrial / nodal RT shall not exceed eight weeks (56 days)
Interventions
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Weekly cisplatin with RT
Cisplatin 40mg/m2 IV Weekly For 6 Cycles.(The 6th cycle of cisplatin may be omitted if external beam radiation therapy has been completed) Cisplatin may be diluted and administered per established institutional guidelines. For general suggestion, 40 mg/ m2 of cisplatin may be diluted in 250 ml 0.9% sodium chloride and administered over one or two hours.
Cisplatin will be given on the first day of external RT (Day 1), preferably, and must be given prior to radiation treatment on that day
External beam RT will be followed by intracavitary brachytherapy. The total elapsed time for completion of external beam to the whole pelvis, intracavitary BT, and parametrial / nodal RT shall not exceed eight weeks (56 days)
Tri-weekly cisplatin with RT
Tri-weekly cisplatin 75mg/m2 three cycles concurrent to radiation therapy
Cisplatin may be diluted and administered per established institutional guidelines. For general suggestion, 75 mg/m2 of cisplatin may be diluted in 500 ml 0.9% sodium chloride and administered over one or two hours (rate of 1 mg of cisplatin per minute).
Cisplatin will be given on the first day of external RT (Day 1), preferably, and must be given prior to radiation treatment on that day.
External beam RT will be followed by intracavitary brachytherapy. The total elapsed time for completion of external beam to the whole pelvis, intracavitary BT, and parametrial / nodal RT shall not exceed eight weeks (56 days)
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* 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 requirements
Exclusion Criteria
* 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)
18 Years
75 Years
FEMALE
No
Sponsors
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Seoul National University Hospital
OTHER
Asan Medical Center
OTHER
Gangnam Severance Hospital
OTHER
Korea Cancer Center Hospital
OTHER
Responsible Party
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Sang-Young Ryu
Chair of Cerivcal/Ovarian Cancer Center
Principal Investigators
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SANG YOUNG SY RYU, M.D.
Role: PRINCIPAL_INVESTIGATOR
STAFF
SARIKAPAN WILAILAK, M.D.
Role: PRINCIPAL_INVESTIGATOR
Ramathibodi Hospital
Locations
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Fudan University Shanghai Cancer Center
Shanghai, , China
Dongnam Inst.of Radiological/Medical Science
Busan, , South Korea
Soon Chun Hyang University Hospital
Cheonan, , South Korea
Dongsan Medical Center
Daegu, , South Korea
Asan Medical Center
Seoul, , South Korea
Ewha Womans University Mokdong Hospital
Seoul, , South Korea
Gachon University Gil Hospital
Seoul, , South Korea
Gangnam Severance Hospital
Seoul, , South Korea
Korea Cancer Center Hospital, Korea Institute of Radiological & Medical Sciences
Seoul, , South Korea
Korea University Guro Hospital
Seoul, , South Korea
Kyungpook National University Hospital
Seoul, , South Korea
Seoul National University Hospital
Seoul, , South Korea
Severance Hospital/Sinchon Severance Hospital
Seoul, , South Korea
Faculty of Medicine, Ramathibodi Hospital, Mahidol University
Bangkok, , Thailand
Ho Chi Minh City Oncology Hospital
Ho Chi Minh City, , Vietnam
Countries
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Central Contacts
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Facility Contacts
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Gui Hao Ke
Role: primary
Sang-IL Park
Role: primary
Seob Jeon
Role: primary
Chi-Heum Cho
Role: primary
Joo-Hyun Nam
Role: primary
Seung Cheol Kim
Role: primary
Gwang Beom Lee
Role: primary
Jae-Hoon Kim
Role: primary
Jin Hwa Hong
Role: primary
Sun-joo Lee
Role: primary
Hak Jae Kim
Role: primary
Young Tae Kim
Role: primary
Thinh Dang huy Quoc
Role: primary
References
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Other Identifiers
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KGOG 1027/THAI 2012
Identifier Type: -
Identifier Source: org_study_id
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