Trial Title:
Cervical Boost by Ablative Stereotactic Radiotherapy (SABR) vs Brachytherapy in Patients With Cervical Carcinoma
NCT ID:
NCT06560697
Condition:
Uterine Cervical Neoplasm
Conditions: Official terms:
Uterine Cervical Neoplasms
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Randomized open-label phase 2 study in people with CaCu clinical stages IB3-IIIC1 treated
with QT/RT. Subjects will be randomized to cervical boost with SBRT or 3D intracavitary
brachytherapy in a 1:1 ratio and stratified by nodal status.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Radiation
Intervention name:
SABR VS Intracavitary 3D Brachytherapy
Description:
Arm 1 will be the experimental arm and will consist of patients with CC clinical stages
IB3-IIIC1 who will be treated with CT/RT with a minimum dose of 45Gy and boost in the
case of macroscopic nodes (1.8Gy 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 EQD210(Gy) at PTV D90% of 83.9Gy. Arm 2 will be the control arm that will
consist of patients with CC clinical stages IB3-IIIC1 and will be treated with CT/RT with
a minimum dose of 45Gy and boost in the case of macroscopic nodes (1.8Gy 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 EQD210(Gy) at point A of 83.9Gy.
Arm group label:
Cervical Boost with Intracavitary Brachytherapy
Arm group label:
Cervical Boost with SABR
Summary:
Background Cervical cancer (CaCu) is the fourth cause of death in women. In patients with
locally advanced disease, the treatment of choice is CT/RT, 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 CT/RT 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 QT/RT + SBRT vs QT/RT + Brachytherapy. It will include patients with IB3-IIIC1
CaCu >18 years of age with adequate renal function. They will be randomized 1:1 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 QT/RT 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 CT/RT 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 CT/RT using the CTCAE V5.0 criteria.
2. Evaluate local efficacy and objective response using the RECIST 1.1 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 patient's 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 QT/RT. Subjects will be randomized to cervical boost with SBRT or 3D intracavitary
brachytherapy in a 1:1 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 CT/RT with a minimum dose of 45Gy and boost in the
case of macroscopic nodes (1.8Gy 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 EQD210(Gy) at PTV D90% of 83.9Gy. Arm 2 will be the control arm that will
consist of patients with CC clinical stages IB3-IIIC1 and will be treated with CT/RT with
a minimum dose of 45Gy and boost in the case of macroscopic nodes (1.8Gy 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 EQD210(Gy) at point A of 83.9Gy.
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
26.7% at 2 years. For intracavitary brachytherapy, a grade 3 late toxicity of 3.31% has
been reported.
The sample size was calculated using a formula for 2 proportions, in which an incidence
of grade 3-4 toxicity of 26.7% for arm A and 3.31% 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 PET/CT according to REC 1.1 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 >10g/L. (With the possibility of transfusion prior to
treatment to reach this hemoglobin level).
Leukocytes >4000/mm3. Platelets>100,000mm3. Neutrophils >1500 / μL
Hepatic:
Total bilirubin <1.5 X times the normal value. Transaminases <1.5 X times the normal
value.
Renal:
Creatinine <1.3mg/dl or creatinine clearance > 40 mL/minute (using the
Cockcroft/Gault formula).
Women: DepCr = (140 - Age in years) x Weight in kg x 0.85
___________________________________ 72 x Serum Creatinine in mg/dL Men: DepCr = (140
- Age in years) x Weight in kg x 1.00
_____________________________________ 72 x Serum Creatinine in mg/dL
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 >40kg/m2 according to the World Health
Organization: Patients treated with pelvic radiotherapy and a body mass index
>40kg/m2 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 mg/m2).
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 patient's safety and compliance with the protocol
at risk.
24. Patients with a percentage of rectal circumference receiving a dose of 15Gy >62.7%.
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.
Criteria for eligibility:
Criteria:
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 PET/CT according to REC 1.1 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 >10g/L. (With the possibility of transfusion prior to
treatment to reach this hemoglobin level).
Leukocytes >4000/mm3. Platelets>100,000mm3. Neutrophils >1500 / μL
Hepatic:
Total bilirubin <1.5 X times the normal value. Transaminases <1.5 X times the normal
value.
Renal:
Creatinine <1.3mg/dl or creatinine clearance > 40 mL/minute (using the
Cockcroft/Gault formula).
Women: DepCr = (140 - Age in years) x Weight in kg x 0.85
___________________________________ 72 x Serum Creatinine in mg/dL Men: DepCr = (140
- Age in years) x Weight in kg x 1.00
_____________________________________ 72 x Serum Creatinine in mg/dL
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 >40kg/m2 according to the World Health
Organization: Patients treated with pelvic radiotherapy and a body mass index
>40kg/m2 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 mg/m2).
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 patient's safety and compliance with the protocol
at risk.
24. Patients with a percentage of rectal circumference receiving a dose of 15Gy >62.7%
Gender:
Female
Gender based:
Yes
Gender description:
People with uterine cervix carcinoma
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Instituto Nacional de Cancerologia
Address:
City:
Mexico City
Country:
Mexico
Status:
Recruiting
Contact:
Last name:
Christian H Flores-Balcazar, phD
Phone:
5554247238
Email:
christian.floresb@incmnsz.mx
Start date:
May 15, 2024
Completion date:
December 31, 2030
Lead sponsor:
Agency:
National Institute of Cancerología
Agency class:
Other
Collaborator:
Agency:
National Institute of Medical Sciences and Nutrition, Salvador Zubiran
Agency class:
Other
Source:
National Institute of Cancerología
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06560697
