Cervical CancerPhase 3TACONCT01561586
Tri-weekly Cisplatin Based Chemoradiation in Locally Advanced Cervical Cancer
A Phase 3 study testing Weekly cisplatin with RT and Tri-weekly cisplatin with RT in people with Cervical Cancer, run by Korea Cancer Center Hospital at 15 sites in 4 countries.
Trial summary
Current standard treatment for locally advanced cervical cancer is cisplatin-based concurrent chemoradiation (CRT). 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… Read more about this study
- Who is it for?
- Ages 18 to 75 years, women only
- Conditions the study is for
- Cervical Cancer
- What is being tested?
- Weekly cisplatin with RT and Tri-weekly cisplatin with RT
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 374 participants
- Where
- 15 sitesin 4 countries
- Study dates
- Mar 2012to Mar 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
15 sites in 4 countries.
15 sites in 4 countries
South Korea12 sites, 12 recruiting
- Recruiting
Dongnam Inst.of Radiological/Medical Science
Busan
Sang-IL Park
- Recruiting
Soon Chun Hyang University Hospital
Cheonan
Seob Jeon
- Recruiting
Dongsan Medical Center
Daegu
Chi-Heum Cho
- Recruiting
Asan Medical Center
Seoul
Joo-Hyun Nam
- Recruiting
Ewha Womans University Mokdong Hospital
Seoul
Seung Cheol Kim
- Recruiting
Gachon University Gil Hospital
Seoul
Gwang Beom Lee
- Recruiting
Gangnam Severance Hospital
Seoul
Jae-Hoon Kim
- Recruiting
Korea Cancer Center Hospital, Korea Institute of Radiological & Medical Sciences
Seoul
SANG YOUNG RYU, M.D., 82-2-970-1227, ryu@kcch.re.kr
SANG YOUNG RYU, M.D.
- Recruiting
Korea University Guro Hospital
Seoul
Jin Hwa Hong
- Recruiting
Kyungpook National University Hospital
Seoul
Sun-joo Lee
- Recruiting
Seoul National University Hospital
Seoul
Hak Jae Kim
- Recruiting
Severance Hospital/Sinchon Severance Hospital
Seoul
Young Tae Kim
China1 site, 1 recruiting
- Recruiting
Fudan University Shanghai Cancer Center
Shanghai
Gui Hao Ke
Thailand1 site, 1 recruiting
- Recruiting
Faculty of Medicine, Ramathibodi Hospital, Mahidol University
Bangkok
SARIKAPAN WILAILAK, M.D., 66-2-2011451, raswl@mahidol.ac.th
SARIKAPAN WILAILAK, M.D.
Vietnam1 site, 1 recruiting
- Recruiting
Ho Chi Minh City Oncology Hospital
Ho Chi Minh City
Thinh Dang huy Quoc
About this study
Official title: Randomized Phase III Clinical Trial of Weekly Versus Tri-weekly Cisplatin Based Chemoradiation in Locally Advanced Cervical Cancer
Current standard treatment for locally advanced cervical cancer is cisplatin-based concurrent chemoradiation (CRT). 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.
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.
Read the detailed description
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.
- Conditions
- Cervical Cancer
- Being tested
- Weekly cisplatin with RT, Tri-weekly cisplatin with RT
- Keywords
- Cervical cancer, Concurrent chemoradiation, Cisplatin
- Medical subject headings
- Uterine Cervical Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Weekly cisplatin with RTDrug
Also called Cisplatin
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 RTDrug
Also called Cisplatin
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)
| Study group | Role | What they receive |
|---|---|---|
| A: Weekly cisplatin with RT | Active comparator | Weekly cisplatin 40mg/m2 six cycles concurrent to radiation therapy Receives: Drug: Weekly cisplatin with RT |
| B: Tri-weekly cisplatin with RT | Experimental | Tri-weekly cisplatin 75mg/m2 three cycles concurrent to radiation therapy Receives: Drug: Tri-weekly cisplatin with RT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival
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.
Measured: From entry into the study to 5 year after treatment or death
Secondary outcomes (4)
Progression Free Survival
The time from randomization to the time of disease progression as determined by the investigator (by clinical, radiological or pathological means) or death from any cause
Measured: 5 year after treatment
Recurrence rate
Clinical, radiological or histological reoccurrence of disease since study entry.
Site of First Recurrence (e.g. para-aortic or supraclavicular lymph nodes, lung, liver, bone, etc.) will also be documented.
Measured: 5 year after therapy
Adverse events
Adverse event is any untoward medical occurrence in a patient or clinical investigational subject administered a study treatment and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An adverse event is any adverse change (developing or worsening) from the patient's pre-treatment condition, including intercurrent illness.
Measured: 5 years after therapy
Compliance to radiation protocol
Variation acceptable:
- Total treatment completed within 56 days (+20% = 67 days)
- Total dose received to Point A inclusive of EBRT and BT = 80 - 86.4 Gy +/- 5%
Deviation unacceptable:
- Total treatment greater than 67 days
- Total dose received at Point A less than 76 Gy or greater than 90.7 Gy
Measured: 56~ 67 days after treatment start
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2012 (estimated)
- Study startMar 2012
- Primary completionMar 2020 (estimated)
- Study completionMar 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (39)Papers the sponsor has linked to this study.
- Other trials for Cervical CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 374 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Korea Cancer Center Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Seoul National University Hospital, Asan Medical Center, Gangnam Severance Hospital
- Responsible party
- Principal investigator, Sang-Young Ryu, Korea Cancer Center Hospital
- Investigators
- SANG YOUNG SY RYU, M.D., Principal investigator, STAFFSARIKAPAN WILAILAK, M.D., Principal investigator, Ramathibodi Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01561586
- Sponsor's protocol ID
- KGOG 1027/THAI 2012
- Acronym
- TACO
- Status last verified
- Feb 2019
- First submitted
- 20 Mar 2012
- Last updated
- 27 Feb 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Garcia AA, Blessing JA, Darcy KM, Lenz HJ, Zhang W, Hannigan E, Moore DH. Phase II clinical trial of capecitabine in the treatment of advanced, persistent or recurrent squamous cell carcinoma of the cervix with translational research: a gynecologic oncology group study. Gynecol Oncol. 2007 Mar;104(3):572-9. doi: 10.1016/j.ygyno.2006.09.002. Epub 2006 Oct 17.
PubMed 17049588Keys HM, Bundy BN, Stehman FB, Muderspach LI, Chafe WE, Suggs CL 3rd, Walker JL, Gersell D. Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. N Engl J Med. 1999 Apr 15;340(15):1154-61. doi: 10.1056/NEJM199904153401503.
PubMed 10202166Morris M, Eifel PJ, Lu J, Grigsby PW, Levenback C, Stevens RE, Rotman M, Gershenson DM, Mutch DG. Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1137-43. doi: 10.1056/NEJM199904153401501.
PubMed 10202164Peters WA 3rd, Liu PY, Barrett RJ 2nd, Stock RJ, Monk BJ, Berek JS, Souhami L, Grigsby P, Gordon W Jr, Alberts DS. Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol. 2000 Apr;18(8):1606-13. doi: 10.1200/JCO.2000.18.8.1606.
PubMed 10764420Rose PG, Bundy BN, Watkins EB, Thigpen JT, Deppe G, Maiman MA, Clarke-Pearson DL, Insalaco S. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1144-53. doi: 10.1056/NEJM199904153401502.
PubMed 10202165Whitney CW, Sause W, Bundy BN, Malfetano JH, Hannigan EV, Fowler WC Jr, Clarke-Pearson DL, Liao SY. Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study. J Clin Oncol. 1999 May;17(5):1339-48. doi: 10.1200/JCO.1999.17.5.1339.
PubMed 10334517Green JA, Kirwan JM, Tierney JF, Symonds P, Fresco L, Collingwood M, Williams CJ. Survival and recurrence after concomitant chemotherapy and radiotherapy for cancer of the uterine cervix: a systematic review and meta-analysis. Lancet. 2001 Sep 8;358(9284):781-6. doi: 10.1016/S0140-6736(01)05965-7.
PubMed 11564482Chemoradiotherapy for Cervical Cancer Meta-Analysis Collaboration. Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: a systematic review and meta-analysis of individual patient data from 18 randomized trials. J Clin Oncol. 2008 Dec 10;26(35):5802-12. doi: 10.1200/JCO.2008.16.4368. Epub 2008 Nov 10.
PubMed 19001332Kirwan JM, Symonds P, Green JA, Tierney J, Collingwood M, Williams CJ. A systematic review of acute and late toxicity of concomitant chemoradiation for cervical cancer. Radiother Oncol. 2003 Sep;68(3):217-26. doi: 10.1016/s0167-8140(03)00197-x.
PubMed 13129628Lanciano R, Calkins A, Bundy BN, Parham G, Lucci JA 3rd, Moore DH, Monk BJ, O'Connor DM. Randomized comparison of weekly cisplatin or protracted venous infusion of fluorouracil in combination with pelvic radiation in advanced cervix cancer: a gynecologic oncology group study. J Clin Oncol. 2005 Nov 20;23(33):8289-95. doi: 10.1200/JCO.2004.00.0497. Epub 2005 Oct 17.
PubMed 16230678Pearcey R, Brundage M, Drouin P, Jeffrey J, Johnston D, Lukka H, MacLean G, Souhami L, Stuart G, Tu D. Phase III trial comparing radical radiotherapy with and without cisplatin chemotherapy in patients with advanced squamous cell cancer of the cervix. J Clin Oncol. 2002 Feb 15;20(4):966-72. doi: 10.1200/JCO.2002.20.4.966.
PubMed 11844818Ryu SY, Lee WM, Kim K, Park SI, Kim BJ, Kim MH, Choi SC, Cho CK, Nam BH, Lee ED. Randomized clinical trial of weekly vs. triweekly cisplatin-based chemotherapy concurrent with radiotherapy in the treatment of locally advanced cervical cancer. Int J Radiat Oncol Biol Phys. 2011 Nov 15;81(4):e577-81. doi: 10.1016/j.ijrobp.2011.05.002. Epub 2011 Aug 11.
PubMed 21840137Mitsuhashi A, Uno T, Tanaka N, Suzuka K, Tate S, Yamazawa K, Matsui H, Yamamoto S, Ito H, Sekiya S. Phase I study of daily cisplatin and concurrent radiotherapy in patients with cervical carcinoma. Gynecol Oncol. 2005 Jan;96(1):194-7. doi: 10.1016/j.ygyno.2004.09.038.
PubMed 15589600Watanabe Y, Nakai H, Shimaoka M, Tobiume T, Tsuji I, Hoshiai H. Feasibility of concurrent cisplatin use during primary and adjuvant chemoradiation therapy: a phase I study in Japanese patients with cancer of the uterine cervix. Int J Clin Oncol. 2006 Aug;11(4):309-13. doi: 10.1007/s10147-006-0567-4.
PubMed 16937305Bonomi P, Blessing JA, Stehman FB, DiSaia PJ, Walton L, Major FJ. Randomized trial of three cisplatin dose schedules in squamous-cell carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol. 1985 Aug;3(8):1079-85. doi: 10.1200/JCO.1985.3.8.1079.
PubMed 3894589
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Phase III Clinical Trial of Weekly Versus Tri-weekly Cisplatin Based Chemoradiation in Locally Advanced Cervical Cancer
- ClinicalTrials.gov ID
- NCT01561586
- Acronym / sponsor ID
- TACO / KGOG 1027/THAI 2012
- Conditions
- Cervical Cancer
- Keywords
- Cervical cancer, Concurrent chemoradiation, Cisplatin
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 374 participants (estimated)
- Lead sponsor
- Korea Cancer Center HospitalUniversity, hospital or other
- Collaborators
- Seoul National University Hospital, Asan Medical Center, Gangnam Severance Hospital
- Study start
- Mar 2012 (actual)
- Primary completion
- Mar 2020 (estimated)
- Study completion
- Mar 2023 (estimated)
- First posted
- 23 Mar 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Current standard treatment for locally advanced cervical cancer is cisplatin-based concurrent chemoradiation (CRT). 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.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A: Weekly cisplatin with RT | Active comparator | Drug: Weekly cisplatin with RTWeekly cisplatin 40mg/m2 six cycles concurrent to radiation therapy |
| B: Tri-weekly cisplatin with RT | Experimental | Drug: Tri-weekly cisplatin with RTTri-weekly cisplatin 75mg/m2 three cycles concurrent to radiation therapy |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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)
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Weekly cisplatin with RTAlso: CisplatinCisplatin 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) | Drug | A: Weekly cisplatin with RT |
| Tri-weekly cisplatin with RTAlso: CisplatinTri-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) | Drug | B: Tri-weekly cisplatin with RT |
Primary outcome
Overall survival
Time frame: From entry into the study to 5 year after treatment or death
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.
4 secondary outcomes
Progression Free Survival
Time frame: 5 year after treatment
Recurrence rate
Time frame: 5 year after therapy
Adverse events
Time frame: 5 years after therapy
Compliance to radiation protocol
Time frame: 56~ 67 days after treatment start
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2019.
- Background: PubMed 17049588Garcia AA, Blessing JA, Darcy KM, Lenz HJ, Zhang W, Hannigan E, Moore DH. Phase II clinical trial of capecitabine in the treatment of advanced, persistent or recurrent squamous cell carcinoma of the cervix with translational research: a gynecologic oncology group study. Gynecol Oncol. 2007 Mar;104(3):572-9. doi: 10.1016/j.ygyno.2006.09.002. Epub 2006 Oct 17.
- Background: PubMed 10202166Keys HM, Bundy BN, Stehman FB, Muderspach LI, Chafe WE, Suggs CL 3rd, Walker JL, Gersell D. Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. N Engl J Med. 1999 Apr 15;340(15):1154-61. doi: 10.1056/NEJM199904153401503.
- Background: PubMed 10202164Morris M, Eifel PJ, Lu J, Grigsby PW, Levenback C, Stevens RE, Rotman M, Gershenson DM, Mutch DG. Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1137-43. doi: 10.1056/NEJM199904153401501.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
SANG YOUNG SY RYU, M.D. principal investigator
STAFF
SARIKAPAN WILAILAK, M.D. principal investigator
Ramathibodi Hospital
15 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Weekly cisplatin with RT and Tri-weekly cisplatin with RT in people with Cervical Cancer, run by Korea Cancer Center Hospital at 15 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 27 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in South Korea, China, Thailand, Vietnam. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact SANG YOUNG RYU, M.D. (82-2-970-1227, ryu@kcch.re.kr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall survival (time frame: From entry into the study to 5 year after treatment or death). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01561586, which also lists 39 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Feb 2019.