Ignite Creation Date:
2024-10-26 @ 3:38 PM
Last Modification Date:
2024-10-26 @ 3:38 PM
Study NCT ID:
NCT06560697
Status:
RECRUITING
Last Update Posted:
None
First Post:
2024-07-19
Brief Title:
Cervical Boost by Ablative Stereotactic Radiotherapy SABR vs Brachytherapy in Patients With Cervical Carcinoma
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Randomized Phase II Study to Measure the Safety and Efficacy of Concomitant CTRT Followed by Ablative Stereotactic Radiotherapy SABR vs Brachytherapy in Patients With Cervical Carcinoma in Clinical Stage IB3-IIIC1 at INCAN
Status:
RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
SABRVICAL
Brief Summary:
Background Cervical cancer CaCu is the fourth cause of death in women In patients with locally advanced disease the treatment of choice is CTRT followed by additional boosting with brachytherapy BT There is an international decrease in the use of this technique due to financial restrictions Given the difficulties in using brachytherapy as a boost several series have described promising results in local control using boost with highly conformal techniques such as stereotactic body radiotherapy SBRT On the other hand prospective studies are scarce and with controversial results No study has been published that directly compares three-dimensional intracavitary SBRT and BT In this clinical trial the researchers aim to demonstrate that boosting with SBRT is not inferior to intracavitary brachytherapy in patients with CC
Methodology
Primary Objective
To evaluate the safety and efficacy of concomitant CTRT followed by Ablative Body Stereotactic Radiotherapy SBRT vs Brachytherapy in patients with Cervical Cancer in clinical stage IB3-IIIC1 at INCan
Secondary Objectives
The purpose of this study is to evaluate quality of life local efficacy local control and time to local recurrence overall survival disease-free survival and time to distant recurrence
Study Design
SABRVICAL is a meticulously designed randomized two-arm open-label phase II study to compare QTRT SBRT vs QTRT Brachytherapy It will include patients with IB3-IIIC1 CaCu 18 years of age with adequate renal function They will be randomized 11 to the experimental arm or the standard arm
Expected Results and Outlook With this study we aim to assess that the safety and efficacy of concomitant QTRT with cisplatin followed by SBRT is not inferior to boost with brachytherapy in patients with CaCu IB3-IIIC1 The potential impact of this study is significant as it could provide new treatment options for hospitals that do not have brachytherapy or have a prolonged waiting list for this procedure
Methodology
Primary Objective
To evaluate the safety and efficacy of concomitant CTRT followed by Ablative Body Stereotactic Radiotherapy SBRT vs Brachytherapy in patients with Cervical Cancer in clinical stage IB3-IIIC1 at INCan
Secondary Objectives
The purpose of this study is to evaluate quality of life local efficacy local control and time to local recurrence overall survival disease-free survival and time to distant recurrence
Study Design
SABRVICAL is a meticulously designed randomized two-arm open-label phase II study to compare QTRT SBRT vs QTRT Brachytherapy It will include patients with IB3-IIIC1 CaCu 18 years of age with adequate renal function They will be randomized 11 to the experimental arm or the standard arm
Expected Results and Outlook With this study we aim to assess that the safety and efficacy of concomitant QTRT with cisplatin followed by SBRT is not inferior to boost with brachytherapy in patients with CaCu IB3-IIIC1 The potential impact of this study is significant as it could provide new treatment options for hospitals that do not have brachytherapy or have a prolonged waiting list for this procedure
Detailed Description:
A randomized phase 2 trial is required for two reasons
1 The literature lacks enough prospective information In this context a randomized phase 2 study would identify SBRT as a promising experimental treatment that depending on the results could be tested in a phase 3 trial
2 Randomization will provide an adequate control group to serve as a comparator for the experimental arm since non-randomized historical or contemporary controls are not appropriate due to the amount of bias they introduce in patient selection as well as confounders use of 2D brachytherapy instead of 3D or the use of conformal radiotherapy and not intensity-modulated radiotherapy
To evaluate the safety and efficacy of concomitant CTRT followed by SBRT vs high rate 3D Intracavity Brachytherapy in patients with Cervical Cancer in clinical stage IB3-IIIC1 at INCan
1 Evaluate the safety of CTRT using the CTCAE V50 criteria
2 Evaluate local efficacy and objective response using the RECIST 11 criteria
3 Compare the time to local regional and distant recurrence between radiotherapy techniques
4 Compare overall survival and progression-free survival between both radiotherapy techniques
5 Measure the patients quality of life using the QLQ-C30 and QLQ-CX24 questionnaires
Randomized open-label phase 2 study in people with CaCu clinical stages IB3-IIIC1 treated with QTRT Subjects will be randomized to cervical boost with SBRT or 3D intracavitary brachytherapy in a 11 ratio and stratified by nodal status
Arm 1 will be the experimental arm and will consist of patients with CC clinical stages IB3-IIIC1 who will be treated with CTRT with a minimum dose of 45Gy and boost in the case of macroscopic nodes 18Gy per fraction from Monday to Friday with cisplatin and cervical boost with SBRT of 28Gy in 4 fractions administered at least every 40 hours to achieve an EQD210Gy at PTV D90 of 839Gy Arm 2 will be the control arm that will consist of patients with CC clinical stages IB3-IIIC1 and will be treated with CTRT with a minimum dose of 45Gy and boost in the case of macroscopic nodes 18Gy per fraction from Monday to Friday with cisplatin and cervical boost with high-dose-rate 3D brachytherapy with a dose of 28Gy in 4 fractions administered at least every 40 hours to achieve an EQD210Gy at point A of 839Gy
Sample size The maximum acceptable toxicity grade 3 or higher is 24 The only phase II clinical trial published in the literature about SBRT in CC reported late toxicity of 267 at 2 years For intracavitary brachytherapy a grade 3 late toxicity of 331 has been reported
The sample size was calculated using a formula for 2 proportions in which an incidence of grade 3-4 toxicity of 267 for arm A and 331 for group B was considered A α error of 5 and a power of 80 A total of 35 patients for each arm are needed plus a 20 loss 42 patients for each arm see figure attached
Inclusion criteria
1 People with cervical cancer 18 years of age
2 Signed informed consent form approved by the regulatory committees of both institutes and obtained before each procedure related to the protocol and that is not considered part of the normal care of the patient
3 Able to comply with scheduled visits treatment schedules laboratory and imaging studies and completing quality of life questionnaires
4 Histological confirmation of CaCu and staged as IB3-IIIC1
5 Squamous cell adenosquamous or adenocarcinoma histology
6 No prior treatment for cervical cancer
7 With disease measurable by CT MRI or PETCT according to REC 11 criteria This measurement must be carried out 28 days before randomization
8 Functional status of 0-2 according to WHO criteria
9 Charlson Comorbidity Index of 1-4
10 Candidates to receive cisplatin
11 Normal hematological kidney and hepatic function according to
Hematological
Hemoglobin equal to or 10gL With the possibility of transfusion prior to treatment to reach this hemoglobin level
Leukocytes 4000mm3 Platelets100000mm3 Neutrophils 1500 μL
Hepatic
Total bilirubin 15 X times the normal value Transaminases 15 X times the normal value
Renal
Creatinine 13mgdl or creatinine clearance 40 mLminute using the CockcroftGault formula
Women DepCr 140 - Age in years x Weight in kg x 085
___________________________________ 72 x Serum Creatinine in mgdL Men DepCr 140 - Age in years x Weight in kg x 100
_____________________________________ 72 x Serum Creatinine in mgdL
12 Chest tomography without metastatic disease or infectious diseases
13 Negative pregnancy test in women of childbearing age
14 Not a candidate for another clinical trial within the institution
Exclusion Criteria
1 Patients with small-cell carcinoma or other rare histologies glassy cell carcinoma melanoma sarcomas lymphomas
2 Patients with non-measurable disease
3 Patients in whom pregnancy is confirmed during the recruitment procedure
4 Clinical stages IIIC2-IVB
5 Serious infections or diseases that can be reactivated with the use of chemotherapy or that could limit its use hepatitis or HIV
6 Pre-existing neuropathy of any etiology
7 Concomitant treatment with another experimental drug
8 Mental illnesses With the intention of maximizing adherence to the study those patients who are at risk of imminent physical aggression evident during the interview have intellectual disabilities or autism and who come for consultation due to coercion will not be included in the study their accompanying Severe major depressive disorder with or without psychotic symptoms patients in whom a psychiatric diagnosis coexists in addition to the abuse of some recreational substance eating disorders schizophrenia or Bipolar-type Schizoaffective Disorder
9 Grade 3 obesity with body mass index 40kgm2 according to the World Health Organization Patients treated with pelvic radiotherapy and a body mass index 40kgm2 are associated with a decrease in quality of life due to sexual intestinal genitourinary alterations as well as greater toxicity due to oncological treatments offered such as intracavitary brachyter in which the positioning of the equipment in the vaginal area is significantly difficult in sedated patients Patients with grade III obesity will not be included
10 Any patient who is absent from follow-up for 5 subsequent appointments will be excluded from the study
11 History of total or partial hysterectomy
12 Patients with a history of neoadjuvant chemotherapy or use of another antineoplastic drug differ from cisplatin 40 mgm2
13 History of use of Bevacizumab to manage a pathology other than CC or intention to use this drug as part of the treatment of CC
15 Charlson Comorbidity Index 5 16 Synchronous Cancer except non-melanoma Skin Cancer 17 History of pelvic irradiation for metachronous cancer 18 Inflammatory bowel disease or collagen diseases 19 Patients with severe immunosuppression transplant or treatment with immunosuppressive drugs
20 Patients who do not sign the informed consent form 21 Suspected alcohol or recreational drug abuse 22 Participation in any other clinical trial in the last 90 days prior to protocol recruitment
23 Any illness or disability not covered by the exclusion criteria that in the researchers opinion may put the patients safety and compliance with the protocol at risk
24 Patients with a percentage of rectal circumference receiving a dose of 15Gy 627
Elimination Criteria
A patient will be removed from the study for the following reasons
1 If the patient requests it
2 Inappropriate inclusion in the study without following the inclusion and exclusion criteria
1 The literature lacks enough prospective information In this context a randomized phase 2 study would identify SBRT as a promising experimental treatment that depending on the results could be tested in a phase 3 trial
2 Randomization will provide an adequate control group to serve as a comparator for the experimental arm since non-randomized historical or contemporary controls are not appropriate due to the amount of bias they introduce in patient selection as well as confounders use of 2D brachytherapy instead of 3D or the use of conformal radiotherapy and not intensity-modulated radiotherapy
To evaluate the safety and efficacy of concomitant CTRT followed by SBRT vs high rate 3D Intracavity Brachytherapy in patients with Cervical Cancer in clinical stage IB3-IIIC1 at INCan
1 Evaluate the safety of CTRT using the CTCAE V50 criteria
2 Evaluate local efficacy and objective response using the RECIST 11 criteria
3 Compare the time to local regional and distant recurrence between radiotherapy techniques
4 Compare overall survival and progression-free survival between both radiotherapy techniques
5 Measure the patients quality of life using the QLQ-C30 and QLQ-CX24 questionnaires
Randomized open-label phase 2 study in people with CaCu clinical stages IB3-IIIC1 treated with QTRT Subjects will be randomized to cervical boost with SBRT or 3D intracavitary brachytherapy in a 11 ratio and stratified by nodal status
Arm 1 will be the experimental arm and will consist of patients with CC clinical stages IB3-IIIC1 who will be treated with CTRT with a minimum dose of 45Gy and boost in the case of macroscopic nodes 18Gy per fraction from Monday to Friday with cisplatin and cervical boost with SBRT of 28Gy in 4 fractions administered at least every 40 hours to achieve an EQD210Gy at PTV D90 of 839Gy Arm 2 will be the control arm that will consist of patients with CC clinical stages IB3-IIIC1 and will be treated with CTRT with a minimum dose of 45Gy and boost in the case of macroscopic nodes 18Gy per fraction from Monday to Friday with cisplatin and cervical boost with high-dose-rate 3D brachytherapy with a dose of 28Gy in 4 fractions administered at least every 40 hours to achieve an EQD210Gy at point A of 839Gy
Sample size The maximum acceptable toxicity grade 3 or higher is 24 The only phase II clinical trial published in the literature about SBRT in CC reported late toxicity of 267 at 2 years For intracavitary brachytherapy a grade 3 late toxicity of 331 has been reported
The sample size was calculated using a formula for 2 proportions in which an incidence of grade 3-4 toxicity of 267 for arm A and 331 for group B was considered A α error of 5 and a power of 80 A total of 35 patients for each arm are needed plus a 20 loss 42 patients for each arm see figure attached
Inclusion criteria
1 People with cervical cancer 18 years of age
2 Signed informed consent form approved by the regulatory committees of both institutes and obtained before each procedure related to the protocol and that is not considered part of the normal care of the patient
3 Able to comply with scheduled visits treatment schedules laboratory and imaging studies and completing quality of life questionnaires
4 Histological confirmation of CaCu and staged as IB3-IIIC1
5 Squamous cell adenosquamous or adenocarcinoma histology
6 No prior treatment for cervical cancer
7 With disease measurable by CT MRI or PETCT according to REC 11 criteria This measurement must be carried out 28 days before randomization
8 Functional status of 0-2 according to WHO criteria
9 Charlson Comorbidity Index of 1-4
10 Candidates to receive cisplatin
11 Normal hematological kidney and hepatic function according to
Hematological
Hemoglobin equal to or 10gL With the possibility of transfusion prior to treatment to reach this hemoglobin level
Leukocytes 4000mm3 Platelets100000mm3 Neutrophils 1500 μL
Hepatic
Total bilirubin 15 X times the normal value Transaminases 15 X times the normal value
Renal
Creatinine 13mgdl or creatinine clearance 40 mLminute using the CockcroftGault formula
Women DepCr 140 - Age in years x Weight in kg x 085
___________________________________ 72 x Serum Creatinine in mgdL Men DepCr 140 - Age in years x Weight in kg x 100
_____________________________________ 72 x Serum Creatinine in mgdL
12 Chest tomography without metastatic disease or infectious diseases
13 Negative pregnancy test in women of childbearing age
14 Not a candidate for another clinical trial within the institution
Exclusion Criteria
1 Patients with small-cell carcinoma or other rare histologies glassy cell carcinoma melanoma sarcomas lymphomas
2 Patients with non-measurable disease
3 Patients in whom pregnancy is confirmed during the recruitment procedure
4 Clinical stages IIIC2-IVB
5 Serious infections or diseases that can be reactivated with the use of chemotherapy or that could limit its use hepatitis or HIV
6 Pre-existing neuropathy of any etiology
7 Concomitant treatment with another experimental drug
8 Mental illnesses With the intention of maximizing adherence to the study those patients who are at risk of imminent physical aggression evident during the interview have intellectual disabilities or autism and who come for consultation due to coercion will not be included in the study their accompanying Severe major depressive disorder with or without psychotic symptoms patients in whom a psychiatric diagnosis coexists in addition to the abuse of some recreational substance eating disorders schizophrenia or Bipolar-type Schizoaffective Disorder
9 Grade 3 obesity with body mass index 40kgm2 according to the World Health Organization Patients treated with pelvic radiotherapy and a body mass index 40kgm2 are associated with a decrease in quality of life due to sexual intestinal genitourinary alterations as well as greater toxicity due to oncological treatments offered such as intracavitary brachyter in which the positioning of the equipment in the vaginal area is significantly difficult in sedated patients Patients with grade III obesity will not be included
10 Any patient who is absent from follow-up for 5 subsequent appointments will be excluded from the study
11 History of total or partial hysterectomy
12 Patients with a history of neoadjuvant chemotherapy or use of another antineoplastic drug differ from cisplatin 40 mgm2
13 History of use of Bevacizumab to manage a pathology other than CC or intention to use this drug as part of the treatment of CC
15 Charlson Comorbidity Index 5 16 Synchronous Cancer except non-melanoma Skin Cancer 17 History of pelvic irradiation for metachronous cancer 18 Inflammatory bowel disease or collagen diseases 19 Patients with severe immunosuppression transplant or treatment with immunosuppressive drugs
20 Patients who do not sign the informed consent form 21 Suspected alcohol or recreational drug abuse 22 Participation in any other clinical trial in the last 90 days prior to protocol recruitment
23 Any illness or disability not covered by the exclusion criteria that in the researchers opinion may put the patients safety and compliance with the protocol at risk
24 Patients with a percentage of rectal circumference receiving a dose of 15Gy 627
Elimination Criteria
A patient will be removed from the study for the following reasons
1 If the patient requests it
2 Inappropriate inclusion in the study without following the inclusion and exclusion criteria
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