Locally Advanced Cervical Cancer
Conditions
Keywords
Durvalumab, Chemoradiotherapy, Locally Advanced Cervical Cancer
Brief summary
This is a randomized, multi-center, double-blind, placebo-controlled, global, Phase III study to determine the efficacy and safety of durvalumab + Chemoradiotherapy versus Chemoradiotherapy alone as treatment in Women With Locally Advanced Cervical Cancer
Detailed description
Women will be randomized in a 1:1 ratio to receive treatment with concurrent durvalumab + standard of care (SoC) or Placebo + Soc, followed by durvalumab/placebo maintenance for 24 months.
Interventions
BIOLOGICALDurvalumab
IV infusion every 4 weeks
DRUGCisplatin
Platinum based Standard of Care Chemotherapy administered concurrent with radiation therapy
DRUGCarboplatin
For patients enrolled under CSP v2 and prior - platinum based Standard of Care Chemotherapy administered concurrent with radiation therapy
Radiation therapy per standard of care
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
For inclusion in the study, patients should fulfill the following criteria: 1. Female 2. Aged at least 18 years 3. Documented evidence of cervical adenocarcinoma or squamous carcinoma FIGO (2009) Stages IB2 to IIB node positive or FIGO (2009) IIIA-IVA any node 4. No prior chemotherapy or radiotherapy for cervical cancer 5. WHO/ECOG performance status of 0-1 6. At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 Target Lesion at baseline.
Exclusion criteria
Patients should not enter the study if any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) Based on the Investigator Assessment According to RECIST 1.1 or Histopathologic Confirmation of Local Tumour Progression | Tumor assessments start 20 weeks after randomisation then every 12 weeks up to 164 weeks, then every 24 weeks until date of RECIST1.1 defined radiological progression. Assessed up to date of DCO (20-Jan-2022) to a maximum of 32.6 months | PFS defined as time from date of randomisation until date of tumour progression or death by any cause, regardless of whether the patient withdrew from randomized therapy or received another anticancer therapy prior to progression |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (Count) | Time from date of randomisation until date of death by any cause, assessed up to the data cut-off date (3rd July 2023), assessed up to a maximum of 51.7 months | Number of Participants with Overall Survival (OS) where OS was defined as the time from the date of randomisation until death by any cause |
| Overall Survival (Duration) | Time from date of randomisation until date of death by any cause, assessed up to the data cut-off date (3rd July 2023), assessed up to a maximum of 51.7 months | Time from the date of randomisation until death by any cause |
| Progression-free Survival (PFS) Based on the Investigator Assessment According to RECIST 1.1 or Histopathologic Confirmation of Local Tumour Progression, PD-L1 Expression >= 1% | Tumor assessments start 20 weeks after randomisation then every 12 weeks up to 164 weeks, then every 24 weeks until date of RECIST1.1 defined radiological progression. Assessed up to date of DCO (20-Jan-2022) to a maximum of 32.6 months | PFS defined as time from date of randomisation until date of tumour progression or death by any cause, regardless of whether the patient withdrew from randomized therapy or received another anticancer therapy prior to progression |
| Complete Response Rate | Tumor assessments start 20 weeks after randomisation then every 12 weeks up to 164 weeks, then every 24 weeks until date of RECIST1.1 defined radiological progression. Assessed up to date of DCO (20-Jan-2022) to a maximum of 32.6 months | Percentage of evaluable patients with an overall visit response of Complete Response (disappearance of all target and non-target lesions) |
| Duration of Response (DoR) in Patients With Complete Response (CR) | Tumor assessments start 20 weeks after randomisation then every 12 weeks up to 164 weeks, then every 24 weeks until date of RECIST1.1 defined radiological progression. Assessed up to date of DCO (20-Jan-2022) to a maximum of 32.6 months | Time from date of first documented CR until date of documented progression or death in the absence of progression. For patients who did not progress their DoR was their Progression-free survival censoring time |
| Objective Response Rate (ORR) | Tumor assessments start 20 weeks after randomisation then every 12 weeks up to 164 weeks, then every 24 weeks until date of RECIST1.1 defined radiological progression. Assessed up to date of DCO (20-Jan-2022) to a maximum of 32.6 months | Percentage of evaluable patients with an Investigator-assessed visit response of complete response (CR) or partial response (PR). CR defined as disappearance of all target and non-target lesions and no new lesions. PR defined as \>= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new non-target lesion |
Countries
Brazil, Chile, China, Hungary, India, Japan, Mexico, Peru, Philippines, Poland, Russia, South Africa, South Korea, Taiwan, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Durvalumab + SoC CCRT Durvalumab 1500mg IV infusion every 4 weeks plus Standard of Care (SoC) concurrent chemoradiotherapy (CCRT) (chemotherapy for 5 weeks plus external beam radiotherapy and brachytherapy) | 385 |
| Placebo + SoC CCRT Placebo IV infusion every 4 weeks plus Standard of Care (SoC) concurrent chemoradiotherapy (CCRT) (chemotherapy for 5 weeks plus external beam radiotherapy and brachytherapy) | 385 |
| Total | 770 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 90 | 111 |
| Overall Study | Lost to Follow-up | 7 | 7 |
| Overall Study | No longer eligible due to additional cancer diagnosis | 0 | 1 |
| Overall Study | Other | 1 | 1 |
| Overall Study | Withdrawal by Subject | 19 | 16 |
Baseline characteristics
| Characteristic | Durvalumab + SoC CCRT | Placebo + SoC CCRT | Total |
|---|---|---|---|
| Age, Continuous | 49.6 Years STANDARD_DEVIATION 11.74 | 48.8 Years STANDARD_DEVIATION 11.67 | 49.2 Years STANDARD_DEVIATION 11.7 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 47 Participants | 56 Participants | 103 Participants |
| Race/Ethnicity, Customized Asian | 152 Participants | 148 Participants | 300 Participants |
| Race/Ethnicity, Customized Black or African American | 10 Participants | 12 Participants | 22 Participants |
| Race/Ethnicity, Customized Other | 46 Participants | 44 Participants | 90 Participants |
| Race/Ethnicity, Customized White | 130 Participants | 125 Participants | 255 Participants |
| Sex: Female, Male Female | 385 Participants | 385 Participants | 770 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 91 / 385 | 112 / 385 |
| other Total, other adverse events | 373 / 385 | 368 / 384 |
| serious Total, serious adverse events | 113 / 385 | 90 / 384 |
Outcome results
Primary
Progression-free Survival (PFS) Based on the Investigator Assessment According to RECIST 1.1 or Histopathologic Confirmation of Local Tumour Progression
PFS defined as time from date of randomisation until date of tumour progression or death by any cause, regardless of whether the patient withdrew from randomized therapy or received another anticancer therapy prior to progression
Time frame: Tumor assessments start 20 weeks after randomisation then every 12 weeks up to 164 weeks, then every 24 weeks until date of RECIST1.1 defined radiological progression. Assessed up to date of DCO (20-Jan-2022) to a maximum of 32.6 months
Population: Full Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab + SoC CCRT | Progression-free Survival (PFS) Based on the Investigator Assessment According to RECIST 1.1 or Histopathologic Confirmation of Local Tumour Progression | NA Months |
| Placebo + SoC CCRT | Progression-free Survival (PFS) Based on the Investigator Assessment According to RECIST 1.1 or Histopathologic Confirmation of Local Tumour Progression | NA Months |
p-value: 0.17495% CI: [0.65, 1.08]Log Rank
Secondary
Complete Response Rate
Percentage of evaluable patients with an overall visit response of Complete Response (disappearance of all target and non-target lesions)
Time frame: Tumor assessments start 20 weeks after randomisation then every 12 weeks up to 164 weeks, then every 24 weeks until date of RECIST1.1 defined radiological progression. Assessed up to date of DCO (20-Jan-2022) to a maximum of 32.6 months
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Durvalumab + SoC CCRT | Complete Response Rate | 42.9 Percentage of Participants |
| Placebo + SoC CCRT | Complete Response Rate | 40.3 Percentage of Participants |
p-value: 0.46995% CI: [0.833, 1.487]Regression, Logistic
Secondary
Duration of Response (DoR) in Patients With Complete Response (CR)
Time from date of first documented CR until date of documented progression or death in the absence of progression. For patients who did not progress their DoR was their Progression-free survival censoring time
Time frame: Tumor assessments start 20 weeks after randomisation then every 12 weeks up to 164 weeks, then every 24 weeks until date of RECIST1.1 defined radiological progression. Assessed up to date of DCO (20-Jan-2022) to a maximum of 32.6 months
Population: Full Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab + SoC CCRT | Duration of Response (DoR) in Patients With Complete Response (CR) | NA Months |
| Placebo + SoC CCRT | Duration of Response (DoR) in Patients With Complete Response (CR) | NA Months |
Secondary
Objective Response Rate (ORR)
Percentage of evaluable patients with an Investigator-assessed visit response of complete response (CR) or partial response (PR). CR defined as disappearance of all target and non-target lesions and no new lesions. PR defined as \>= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new non-target lesion
Time frame: Tumor assessments start 20 weeks after randomisation then every 12 weeks up to 164 weeks, then every 24 weeks until date of RECIST1.1 defined radiological progression. Assessed up to date of DCO (20-Jan-2022) to a maximum of 32.6 months
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Durvalumab + SoC CCRT | Objective Response Rate (ORR) | 82.6 Percentage of Participants |
| Placebo + SoC CCRT | Objective Response Rate (ORR) | 80.5 Percentage of Participants |
p-value: 0.46595% CI: [0.794, 1.657]Regression, Logistic
Secondary
Overall Survival (Count)
Number of Participants with Overall Survival (OS) where OS was defined as the time from the date of randomisation until death by any cause
Time frame: Time from date of randomisation until date of death by any cause, assessed up to the data cut-off date (3rd July 2023), assessed up to a maximum of 51.7 months
Population: Full Analysis Set
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Durvalumab + SoC CCRT | Overall Survival (Count) | Died | 91 Participants |
| Durvalumab + SoC CCRT | Overall Survival (Count) | Censored (includes subjects who withdrew consent and subjects who were lost to follow up) | 294 Participants |
| Placebo + SoC CCRT | Overall Survival (Count) | Died | 112 Participants |
| Placebo + SoC CCRT | Overall Survival (Count) | Censored (includes subjects who withdrew consent and subjects who were lost to follow up) | 273 Participants |
Secondary
Overall Survival (Duration)
Time from the date of randomisation until death by any cause
Time frame: Time from date of randomisation until date of death by any cause, assessed up to the data cut-off date (3rd July 2023), assessed up to a maximum of 51.7 months
Population: Full Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab + SoC CCRT | Overall Survival (Duration) | NA Months |
| Placebo + SoC CCRT | Overall Survival (Duration) | NA Months |
p-value: 0.09195% CI: [0.6, 1.04]Log Rank
Secondary
Progression-free Survival (PFS) Based on the Investigator Assessment According to RECIST 1.1 or Histopathologic Confirmation of Local Tumour Progression, PD-L1 Expression >= 1%
PFS defined as time from date of randomisation until date of tumour progression or death by any cause, regardless of whether the patient withdrew from randomized therapy or received another anticancer therapy prior to progression
Time frame: Tumor assessments start 20 weeks after randomisation then every 12 weeks up to 164 weeks, then every 24 weeks until date of RECIST1.1 defined radiological progression. Assessed up to date of DCO (20-Jan-2022) to a maximum of 32.6 months
Population: PD-L1 Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab + SoC CCRT | Progression-free Survival (PFS) Based on the Investigator Assessment According to RECIST 1.1 or Histopathologic Confirmation of Local Tumour Progression, PD-L1 Expression >= 1% | NA Months |
| Placebo + SoC CCRT | Progression-free Survival (PFS) Based on the Investigator Assessment According to RECIST 1.1 or Histopathologic Confirmation of Local Tumour Progression, PD-L1 Expression >= 1% | NA Months |
p-value: 0.20395% CI: [0.64, 1.1]Log Rank