Ignite Creation Date:
2024-05-05 @ 11:58 AM
Last Modification Date:
2024-10-26 @ 9:17 AM
Study NCT ID:
NCT00193739
Status:
UNKNOWN
Last Update Posted:
2019-09-20
First Post:
2005-09-11
Brief Title:
Neoadjuvant Chemotherapy Followed by Surgery Versus Concurrent Chemoradiation in Carcinoma of the Cervix
Sponsor:
Tata Memorial Hospital
Organization:
Tata Memorial Hospital
Study Overview
Official Title:
A Prospective Randomized Trial of Neoadjuvant Chemotherapy and Surgery Versus Concurrent Chemoradiation Therapy in Patients With Stage IB2-IIB Squamous Carcinoma of the Uterine Cervix
Status:
UNKNOWN
Status Verified Date:
2019-09
Last Known Status:
ACTIVE_NOT_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
NACTcervix
Brief Summary:
Carcinoma cervix is a common malignancy in women in developing countries including India The standard treatment of locally advanced cervical cancer Stages IB2 to IIIBis concomitant chemoradiation CT RT using platinum based chemotherapy Some studies including a meta-analysis conducted by the Cochrane group have indicated that few courses of neoadjuvant chemotherapy NACT followed by surgery may be superior to radical radiation alone for these patients However NACT-Surgery approach has never been compared to the current standard of concomitant CT RT The present study is undertaken to compare in a randomized trial NACT3 courses of paclitaxel-carboplatin followed by surgery to concomitant CT RT in stages IB2 to IIB squamous cell carcinoma of the uterine cervix
Detailed Description:
Cancer of the uterine cervix is a major health problem in the developing countries including India and is the commonest cancer amongst women in India with nearly 100000 new women diagnosed to have this cancer every year It is also the main cause of cancer related mortality among women in India At the Tata Memorial Hospital approximately 1600 new patients with cervical cancer are registered every year of which nearly 70 present in locally advanced stages
A majority of patients diagnosed with stage IB cervical cancer in India have bulky tumours more than 4 cm in size and have now been classified as stage IB2 as per the new FIGO staging 1 These tumours are associated with a high incidence of pelvic lymph node metastases Finan et al 2 noted positive pelvic nodes in 155 of patients with stage Ib1 disease versus 438 with stage Ib2 Positive paraaortic nodes were present in 18 of patients for stage Ib1 disease versus 63 of patients with stage Ib2 The result of radical surgery and radical radiation therapy alone or in combination in these tumours has been reported to be much inferior to stage IB1 tumours 60-65 vs 85-90 five year survival The incidence of pelvic lymph node metastasis and the results of treatment of stage IB2 tumours are more or less similar to those with stage IIB tumours
The ability of radiotherapy or surgery to cure locally advanced cervical cancer is limited by the size of the tumour high incidence of pelvic lymph node metastases and potential for systemic spread Besides the doses required to treat large tumours exceed the limit of toxicity in normal tissue Efforts to overcome this problem have included the use of different chemotherapy drugs in different schedules Chemotherapy has been used in the management of locally advanced cervical cancers along with radiation therapy and surgery in different ways eg neoadjuvant adjuvant and concurrent
The standard approach to using chemotherapy in the treatment of patients with locally advanced disease is the use of concurrent chemoradiation The concurrent use of single drug and multiple drug regimens with radiotherapy has been tested in women with cervical cancer Recent data from prospective randomised trials and two meta-analyses 3-12 has unequivocally shown significant survival advantage both disease free and overall survival with the use of concurrent chemoradiation using platinum based chemotherapy compared to radical radiation alone in patients with locally advanced cervical cancer stages IB2-IIIB A significant reduction in distant metastases was also noted in the concurrent chemoradiation therapy arm This has led to acceptance of concurrent chemoradiation therapy as the new standard of care for locally advanced cervical cancer The meta-analyses of these trials showed that the beneficial effect on survival was more evident in stage IB2 and stage II B tumours compared to stage III B tumours which constituted only about 35 of total number of patients
An alternative approach is to use chemotherapy prior to local therapy which could be surgery or radiation Some theoretical benefits of neoadjuvant chemotherapy hereinafter abbreviated as NACT like eradication of micrometastases have long been advanced but never proven It certainly helps in the reduction of tumour bulk in some patients with locally advanced disease Some of these latter patients are then able to undergo surgery which is otherwise not possible The downside to NACT is the delay in institution of definitive treatment in the 20 to 30 patients who dont respond to chemotherapy The randomized trials of NACT followed by radiation therapy versus radiation therapy alone showed no improvement in survival 13-19 It is possible that the failure to show a survival benefit with NACT followed by radiation is due to the selection of chemoresistant clones which are also radioresistant A second explanation also advanced for the failure of NACT approach in head and neck cancers is that NACT just selects out the patients the ones who respond who have biologically favourable disease and confers no benefit by itself Surgical removal of the tumour after chemotherapy will however have no interaction with biochemical resistance of the remaining clones It therefore has the potential of providing a benefit additive to chemotherapy and radiotherapy In their papers Sardi et al 20 21 reported on their randomized trial of NACT bleomycin vincristine and cisplatin followed by surgery plus radiation versus either surgery plus radiation or radiation as the control arm in patients with stage 1B 2B and 3B cervical cancer There was a high response rate to NACT in stage 1B patients 90 in 1B1 and 836 in 1B2 The overall survival in the whole group of stage 1B patients was superior in the NACT arm n102 compared to the control arm n103 81 Vs 66 p 0025 The resectability rate among stage 1B2 patients given NACT was 100 n 61 compared to 85 in the controls n 56 In stage 2B the resectability rate in the NACT arm was 80 n 76 compared to 56 in the control arm n 75 However there was no clear survival advantage of the NACT arm over controls in stages 2B and 3B Although this trial has reported a survival advantage of NACT followed by surgery in a subgroup of patients its results are not definitive The treatment offered in the control arm of this trial attempt at surgical removal upfront in stages 1B and 2B or radiation only in stages 2B and 3B was not standard by current standard and the numbers in various groups were small In order to be considered a therapeutic option in locally advanced patients NACT followed by surgery must be compared to the current therapeutic standard which is concurrent chemoradiation The chemotherapeutic options for cervical cancer at present are different from the one used by Sardi et al The combination of ifosfamide and cisplatin or paclitaxel and carboplatin is likely to show a higher response rate compared to the regimen used by Sardi et al which was bleomycin vincristine and cisplatin
Considering these results from the literature it appears logical to compare neoadjuvant chemotherapy followed by surgery with concurrent chemoradiation in patients with stage IB2 to IIB squamous carcinoma of the cervix
A majority of patients diagnosed with stage IB cervical cancer in India have bulky tumours more than 4 cm in size and have now been classified as stage IB2 as per the new FIGO staging 1 These tumours are associated with a high incidence of pelvic lymph node metastases Finan et al 2 noted positive pelvic nodes in 155 of patients with stage Ib1 disease versus 438 with stage Ib2 Positive paraaortic nodes were present in 18 of patients for stage Ib1 disease versus 63 of patients with stage Ib2 The result of radical surgery and radical radiation therapy alone or in combination in these tumours has been reported to be much inferior to stage IB1 tumours 60-65 vs 85-90 five year survival The incidence of pelvic lymph node metastasis and the results of treatment of stage IB2 tumours are more or less similar to those with stage IIB tumours
The ability of radiotherapy or surgery to cure locally advanced cervical cancer is limited by the size of the tumour high incidence of pelvic lymph node metastases and potential for systemic spread Besides the doses required to treat large tumours exceed the limit of toxicity in normal tissue Efforts to overcome this problem have included the use of different chemotherapy drugs in different schedules Chemotherapy has been used in the management of locally advanced cervical cancers along with radiation therapy and surgery in different ways eg neoadjuvant adjuvant and concurrent
The standard approach to using chemotherapy in the treatment of patients with locally advanced disease is the use of concurrent chemoradiation The concurrent use of single drug and multiple drug regimens with radiotherapy has been tested in women with cervical cancer Recent data from prospective randomised trials and two meta-analyses 3-12 has unequivocally shown significant survival advantage both disease free and overall survival with the use of concurrent chemoradiation using platinum based chemotherapy compared to radical radiation alone in patients with locally advanced cervical cancer stages IB2-IIIB A significant reduction in distant metastases was also noted in the concurrent chemoradiation therapy arm This has led to acceptance of concurrent chemoradiation therapy as the new standard of care for locally advanced cervical cancer The meta-analyses of these trials showed that the beneficial effect on survival was more evident in stage IB2 and stage II B tumours compared to stage III B tumours which constituted only about 35 of total number of patients
An alternative approach is to use chemotherapy prior to local therapy which could be surgery or radiation Some theoretical benefits of neoadjuvant chemotherapy hereinafter abbreviated as NACT like eradication of micrometastases have long been advanced but never proven It certainly helps in the reduction of tumour bulk in some patients with locally advanced disease Some of these latter patients are then able to undergo surgery which is otherwise not possible The downside to NACT is the delay in institution of definitive treatment in the 20 to 30 patients who dont respond to chemotherapy The randomized trials of NACT followed by radiation therapy versus radiation therapy alone showed no improvement in survival 13-19 It is possible that the failure to show a survival benefit with NACT followed by radiation is due to the selection of chemoresistant clones which are also radioresistant A second explanation also advanced for the failure of NACT approach in head and neck cancers is that NACT just selects out the patients the ones who respond who have biologically favourable disease and confers no benefit by itself Surgical removal of the tumour after chemotherapy will however have no interaction with biochemical resistance of the remaining clones It therefore has the potential of providing a benefit additive to chemotherapy and radiotherapy In their papers Sardi et al 20 21 reported on their randomized trial of NACT bleomycin vincristine and cisplatin followed by surgery plus radiation versus either surgery plus radiation or radiation as the control arm in patients with stage 1B 2B and 3B cervical cancer There was a high response rate to NACT in stage 1B patients 90 in 1B1 and 836 in 1B2 The overall survival in the whole group of stage 1B patients was superior in the NACT arm n102 compared to the control arm n103 81 Vs 66 p 0025 The resectability rate among stage 1B2 patients given NACT was 100 n 61 compared to 85 in the controls n 56 In stage 2B the resectability rate in the NACT arm was 80 n 76 compared to 56 in the control arm n 75 However there was no clear survival advantage of the NACT arm over controls in stages 2B and 3B Although this trial has reported a survival advantage of NACT followed by surgery in a subgroup of patients its results are not definitive The treatment offered in the control arm of this trial attempt at surgical removal upfront in stages 1B and 2B or radiation only in stages 2B and 3B was not standard by current standard and the numbers in various groups were small In order to be considered a therapeutic option in locally advanced patients NACT followed by surgery must be compared to the current therapeutic standard which is concurrent chemoradiation The chemotherapeutic options for cervical cancer at present are different from the one used by Sardi et al The combination of ifosfamide and cisplatin or paclitaxel and carboplatin is likely to show a higher response rate compared to the regimen used by Sardi et al which was bleomycin vincristine and cisplatin
Considering these results from the literature it appears logical to compare neoadjuvant chemotherapy followed by surgery with concurrent chemoradiation in patients with stage IB2 to IIB squamous carcinoma of the cervix
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None