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

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ClinicalTrials.gov Identifier: NCT03830866
Recruitment Status : Recruiting
First Posted : February 5, 2019
Last Update Posted : October 19, 2020
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE December 4, 2018
First Posted Date  ICMJE February 5, 2019
Last Update Posted Date October 19, 2020
Actual Study Start Date  ICMJE February 15, 2019
Estimated Primary Completion Date August 16, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 4, 2019)
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 ]
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).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 10, 2020)
  • 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 ]
    The analysis of OS will be based on time from date of randomization until the date of death by any cause
  • 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 ]
    The analysis of CR rate will be based on investigator assessments using RECIST 1.1 or histopathologic assessment of local disease progression.
  • 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 ]
    The analysis of ORR will be based on investigator assessments using RECIST 1.1 or histopathologic assessment of local disease progression.
  • 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 ]
    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.
  • 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 ]
    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)
  • 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 ]
    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).
  • 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 ]
    PFS (3 year) will be summarized (using the Kaplan-Meier curve) and presented by treatment arm.
  • 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 ]
    Time from date of randomization until tumor progression or death due to any cause in patients who are PD-L1 positive
  • 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 ]
    Time from date of randomization until date of death by any cause in patients who are PD-L1 positive
Original Secondary Outcome Measures  ICMJE
 (submitted: February 4, 2019)
  • 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 ]
    The analysis of OS will be based on time from date of randomization until the date of death by any cause
  • 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 ]
    The analysis of CR rate will be based on investigator assessments using RECIST 1.1 or histopathologic assessment of local disease progression.
  • 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 ]
    The analysis of ORR will be based on investigator assessments using RECIST 1.1 or histopathologic assessment of local disease progression.
  • 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 ]
    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.
  • 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 ]
    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)
  • 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 ]
    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).
Current Other Pre-specified Outcome Measures
 (submitted: February 4, 2019)
  • Number of participants with adverse events as assessed by Common Toxicity Criteria for Adverse Events (CTCAE v5.0) [ Time Frame: Estimated to be up to 2.5 years ]
    Type, frequency and severity of adverse events (including those from the pre- and post-treatment periods) will be listed according to CTCAE v5.0
  • The safety and tolerability of durvalumab + SoC CCRT compared to placebo + SoC CCRT as assessed by electrocardiograms (ECGs) [ Time Frame: Estimated to be up to 2.5 years ]
    Resting 12-lead ECGs will be assessed by QTcF interval (ms).
  • The safety and tolerability of durvalumab + SoC CCRT compared to placebo + SoC CCRT as assessed by vital signs(pulse rate) in beats per minute. [ Time Frame: Estimated to be up to 2.5 years ]
    Pulse rate will be evaluated according to the schedule of assessments.
  • The safety and tolerability of durvalumab + SoC CCRT compared to placebo + SoC CCRT as assessed by vital signs(temperature) in degree Celsius. [ Time Frame: Estimated to be up to 2.5 years ]
    Temperature will be evaluated according to the schedule of assessments.
  • The safety and tolerability of durvalumab + SoC CCRT compared to placebo + SoC CCRT as assessed by vital signs(respiration rate) in breaths per minute. [ Time Frame: Estimated to be up to 2.5 years ]
    Respiration rate will be evaluated according to the schedule of assessments.
  • The safety and tolerability of durvalumab + SoC CCRT compared to placebo + SoC CCRT as assessed by vital signs(blood pressure). [ Time Frame: Estimated to be up to 2.5 years ]
    Blood pressure will be evaluated according to the schedule of assessments.
  • The safety and tolerability of durvalumab + SoC CCRT compared to placebo + SoC CCRT as assessed by abnormality in clinical chemistry. [ Time Frame: Estimated to be up to 2.5 years ]
    Clinical chemistry will be assessed by liver function(Alanine aminotransferase, Aspartate aminotransferase, albumin, total bilirubin), kidney function (e.g. Urea, Creatinine) and endocrine function(TSH, T3 free,T4 free).
  • The safety and tolerability of durvalumab + SoC CCRT compared to placebo + SoC CCRT as assessed by abnormality in hematology(cells/L). [ Time Frame: Estimated to be up to 2.5 years ]
    Hematology will be assessed by white cell count, platelet count, absolute neutrophil count and absolute lymphocyte count.
  • The safety and tolerability of durvalumab + SoC CCRT compared to placebo + SoC CCRT as assessed by abnormality in hematology(g/L). [ Time Frame: Estimated to be up to 2.5 years ]
    Hematology will be assessed by haemoglobin.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Study of Durvalumab With Chemoradiotherapy for Women With Locally Advanced Cervical Cancer (CALLA)
Official Title  ICMJE 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
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Locally Advanced Cervical Cancer
Intervention  ICMJE
  • Biological: Durvalumab
    IV infusion every 4 weeks
  • Drug: Cisplatin
    Platinum based Standard of Care Chemotherapy administered concurrent with radiation therapy
  • Drug: Carboplatin
    For patients enrolled under CSP v2 and prior - platinum based Standard of Care Chemotherapy administered concurrent with radiation therapy
  • Radiation: external beam radiation therapy (EBRT) + brachytherapy
    Radiation therapy per standard of care
Study Arms  ICMJE
  • Experimental: Durvalumab (intravenous infusion)
    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
    Interventions:
    • Biological: Durvalumab
    • Drug: Cisplatin
    • Drug: Carboplatin
    • Radiation: external beam radiation therapy (EBRT) + brachytherapy
  • Placebo Comparator: Placebo (matching placebo for intravenous infusion)
    placebo + standard of care concurrent chemoradiation therapy(SoC CCRT)
    Interventions:
    • Drug: Cisplatin
    • Drug: Carboplatin
    • Radiation: external beam radiation therapy (EBRT) + brachytherapy
Publications * Mayadev J, Nunes AT, Li M, Marcovitz M, Lanasa MC, Monk BJ. CALLA: Efficacy and safety of concurrent and adjuvant durvalumab with chemoradiotherapy versus chemoradiotherapy alone in women with locally advanced cervical cancer: a phase III, randomized, double-blind, multicenter study. Int J Gynecol Cancer. 2020 Jul;30(7):1065-1070. doi: 10.1136/ijgc-2019-001135. Epub 2020 May 23.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 4, 2019)
714
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 16, 2024
Estimated Primary Completion Date August 16, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Gender Eligibility Description: Female: only female participants are being studied
Ages  ICMJE 18 Years to 130 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Listed Location Countries  ICMJE Japan,   Brazil,   Chile,   China,   Hungary,   India,   Korea, Republic of,   Mexico,   Peru,   Philippines,   Poland,   Russian Federation,   South Africa,   Taiwan,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03830866
Other Study ID Numbers  ICMJE D9100C00001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Urban Scheuring, M.D., Ph.D. AstraZeneca
Principal Investigator: Bradley Monk, M.D University of Arizona, Arizona, USA
PRS Account AstraZeneca
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP