Study of Durvalumab With Chemoradiotherapy for Women With Locally Advanced Cervical Cancer (CALLA)

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase III, Randomized, Multi-Center, Double-Blind, Global Study to Determine the Efficacy and Safety of Durvalumab in Combination With and Following Chemoradiotherapy Compared to Chemoradiotherapy Alone for Treatment in Women With Locally Advanced Cervical Cancer

Conditions
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Locally Advanced Cervical Cancer

Intervention / Treatment
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* Biological: Durvalumab
* Drug: Cisplatin
* Drug: Carboplatin
* Radiation: external beam radiation therapy (EBRT) + brachytherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For inclusion in the study, patients should fulfill the following criteria: Female Aged at least 18 years Documented evidence of cervical adenocarcinoma or squamous carcinoma FIGO (2009) Stages IB2 to IIB node positive or FIGO (2009) IIIA-IVA any node No prior chemotherapy or radiotherapy for cervical cancer WHO/ECOG performance status of 0-1 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 exclusion criteria are fulfilled: Diagnosis of small cell (neuroendocrine) histology or mucinous adenocarcinoma cervical cancer Intent to administer a fertility-sparing treatment regimen Undergone a previous hysterectomy Evidence of metastatic disease per RECIST 1.1 including lymph nodes ≥15 mm (short axis) above the L1 cephalad body, in the inguinal region or outside the planned radiation field. History of allogeneic organ transplantation Active or prior documented autoimmune or inflammatory disorders Uncontrolled intercurrent illness History of another primary malignancy and active primary immunodeficiency

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Durvalumab (intravenous infusion)<br>durvalumab + standard of care concurrent chemoradiation therapy(SoC CCRT) followed by durvalumab monotherapy up to 24 months or until PD from the date of randomization | Biological: Durvalumab<br>* IV infusion every 4 weeks<br>Drug: Cisplatin<br>* Platinum based Standard of Care Chemotherapy administered concurrent with radiation therapy<br>Drug: Carboplatin<br>* For patients enrolled under CSP v2 and prior - platinum based Standard of Care Chemotherapy administered concurrent with radiation therapy<br>Radiation: external beam radiation therapy (EBRT) + brachytherapy<br>* Radiation therapy per standard of care<br>|
| Placebo Comparator: Placebo (matching placebo for intravenous infusion)<br>placebo + standard of care concurrent chemoradiation therapy(SoC CCRT) | Drug: Cisplatin<br>* Platinum based Standard of Care Chemotherapy administered concurrent with radiation therapy<br>Drug: Carboplatin<br>* For patients enrolled under CSP v2 and prior - platinum based Standard of Care Chemotherapy administered concurrent with radiation therapy<br>Radiation: external beam radiation therapy (EBRT) + brachytherapy<br>* Radiation therapy per standard of care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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 | 
| 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 from date of randomisation until date of death by any cause, assessed up to the data cut-off date (20th January 2022), assessed up to a maximum of 34.3 months | 
| Overall Survival (Duration) | Time from the date of randomisation until death by any cause | Time from date of randomisation until date of death by any cause, assessed up to the data cut-off date (20th January 2022), assessed up to a maximum of 34.3 months | 
| 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 | 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 | 
| Complete Response Rate | Percentage of evaluable patients with an overall visit response of Complete Response (disappearance of all target and non-target lesions) | 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 | 
| 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 | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Durvalumab, Chemoradiotherapy, Locally Advanced Cervical Cancer