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

Phase 3

Completed

• Conditions: Locally Advanced Cervical Cancer
• Interventions: Biological: Durvalumab; Drug: Cisplatin; Drug: Carboplatin; Radiation: external beam radiation therapy (EBRT) + brachytherapy

• Registration Number: NCT03830866
• Lead Sponsor: AstraZeneca

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.

Study Timeline

• Study First Submitted: 2018-12-04
• Study First Submitted QC: 2019-02-04
• Study First Posted: 2019-02-05
• Study Start: 2019-02-15
• Primary Completion: 2022-01-20
• Results First Submitted: 2023-01-13
• Results First Submitted QC: 2023-03-02
• Results First Posted: 2023-03-06
• Study Completion: 2023-07-03
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-28
• Last Update Posted: 2024-07-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 770

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.

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Exclusion Criteria

Patients should not enter the study if any of the following exclusion criteria are fulfilled:

1. Diagnosis of small cell (neuroendocrine) histology or mucinous adenocarcinoma cervical cancer
2. Intent to administer a fertility-sparing treatment regimen
3. Undergone a previous hysterectomy
4. 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.
5. History of allogeneic organ transplantation
6. Active or prior documented autoimmune or inflammatory disorders
7. Uncontrolled intercurrent illness
8. History of another primary malignancy and active primary immunodeficiency

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Durvalumab (intravenous infusion)	Durvalumab	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
Durvalumab (intravenous infusion)	Carboplatin	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
Durvalumab (intravenous infusion)	external beam radiation therapy (EBRT) + brachytherapy	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
Placebo (matching placebo for intravenous infusion)	external beam radiation therapy (EBRT) + brachytherapy	placebo + standard of care concurrent chemoradiation therapy(SoC CCRT)
Durvalumab (intravenous infusion)	Cisplatin	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
Placebo (matching placebo for intravenous infusion)	Cisplatin	placebo + standard of care concurrent chemoradiation therapy(SoC CCRT)
Placebo (matching placebo for intravenous infusion)	Carboplatin	placebo + standard of care concurrent chemoradiation therapy(SoC CCRT)

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
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
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
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

Trial Locations

Locations (1)

Research Site; 🇨🇳 Taoyuan City, Taiwan