Description:
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
Title
- Brief Title: Study of Durvalumab With Chemoradiotherapy for Women With Locally Advanced Cervical Cancer (CALLA)
- Official Title: 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
Clinical Trial IDs
- ORG STUDY ID:
D9100C00001
- NCT ID:
NCT03830866
Conditions
- Locally Advanced Cervical Cancer
Interventions
| Drug | Synonyms | Arms |
|---|
| Durvalumab | | Durvalumab (intravenous infusion) |
| Cisplatin | | Durvalumab (intravenous infusion) |
| Carboplatin | | Durvalumab (intravenous infusion) |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Durvalumab (intravenous infusion) | Experimental | 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
- Cisplatin
- Carboplatin
|
| Placebo (matching placebo for intravenous infusion) | Placebo Comparator | placebo + standard of care concurrent chemoradiation therapy(SoC CCRT) | |
Eligibility Criteria
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 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
| Maximum Eligible Age: | 130 Years |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | Female |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | The efficacy of durvalumab + SoC CCRT compared to placebo + SoC CCRT in terms of Progression-Free Survival (PFS) |
| Time Frame: | Estimated to be from the time of randomization up to 4.5 years |
| Safety Issue: | |
| Description: | Progression-Free Survival is defined as the time from randomization until the date of objective disease progression (RECIST 1.1 or histopathologic evidence) or death (by any cause in the absence of progression). |
Secondary Outcome Measures
| Measure: | The efficacy of durvalumab + SoC CCRT compared to placebo + SoC CCRT as assessed by the time from the date of randomization until death due to any cause in terms of Overall Survival (OS) |
| Time Frame: | Estimated to be from the time of randomization up to 5 years |
| Safety Issue: | |
| Description: | The analysis of OS will be based on time from date of randomization until the date of death by any cause |
| Measure: | The efficacy of durvalumab + SoC CCRT compared to placebo + SoC CCRT as assessed by proportion of patients with a complete response at the first tumor assessment after chemoradiotherapy in terms of Complete Response (CR) rate |
| Time Frame: | Estimated to be up to 20 weeks |
| Safety Issue: | |
| Description: | The analysis of CR rate will be based on investigator assessments using RECIST 1.1 or histopathologic assessment of local disease progression. |
| Measure: | The efficacy of durvalumab + SoC CCRT compared to placebo + SoC CCRT as assessed by the number (%) of patients with at least one visit response of Complete Response (CR) or partial response (PR) in terms of Objective Response Rate (ORR) |
| Time Frame: | Estimated to be up to 4.5 years |
| Safety Issue: | |
| Description: | The analysis of ORR will be based on investigator assessments using RECIST 1.1 or histopathologic assessment of local disease progression. |
| Measure: | The efficacy of durvalumab + SoC CCRT compared to placebo + SoC CCRT as assessed by time from detection of CR until the date of disease progression in terms of Duration of Response (DoR) in patients with a Complete Response (CR) |
| Time Frame: | Estimated up to 4.5 years |
| Safety Issue: | |
| Description: | The analysis of DoR in patients with a CR will be based on investigator assessments using RECIST 1.1 or histopathologic confirmation of local disease progression. |
| Measure: | Disease-related symptoms and health related quality of life (HRQoL) in patients treated with durvalumab + SoC CCRT compared with placebo + SoC CCRT as assessed by the change from baseline in disease-related symptoms and HRQoL |
| Time Frame: | Estimated up to 4.5 years |
| Safety Issue: | |
| Description: | The analysis of disease-related symptoms and HRQoL based on European Organization for Research and Treatment of Cancer (EORTC) core cancer instrument (EORTC QLQ-C30) |
| Measure: | Disease-related symptoms and health related quality of life (HRQoL) in patients treated with durvalumab + SoC CCRT compared with placebo + SoC CCRT as assessed by the change from baseline in disease-related symptoms and HRQoL |
| Time Frame: | Estimated up to 4.5 years |
| Safety Issue: | |
| Description: | The analysis of disease-related symptoms and HRQoL based on European Organization for Research and Treatment of Cancer (EORTC) supplemental cervical cancer module (EORTC CX24). |
| Measure: | To further assess the efficacy of durvalumab + SoC CCRT compared with placebo + SoC CCRT in terms of Proportion of patients alive and progression-free at 3 years (PFS 3 year). |
| Time Frame: | Estimated up to 4.5 years |
| Safety Issue: | |
| Description: | PFS (3 year) will be summarized (using the Kaplan-Meier curve) and presented by treatment arm. |
| Measure: | The efficacy of durvalumab + SoC CCRT compared with placebo + SoC CCRT in terms of PFS in PD-L1 positive patients |
| Time Frame: | Estimated up to 4.5 years |
| Safety Issue: | |
| Description: | Time from date of randomization until tumor progression or death due to any cause in patients who are PD-L1 positive |
| Measure: | The efficacy of durvalumab + SoC CCRT compared with placebo + SoC CCRT in terms of OS in PD-L1 positive patients |
| Time Frame: | Estimated up to 5 years |
| Safety Issue: | |
| Description: | Time from date of randomization until date of death by any cause in patients who are PD-L1 positive |
Details
| Phase: | Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | AstraZeneca |
Trial Keywords
- Durvalumab
- Chemoradiotherapy
- Locally Advanced Cervical Cancer
Last Updated
August 16, 2021
