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

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

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

Study Overview

• Status: Completed
• Conditions: Locally Advanced Cervical Cancer
• Intervention / Treatment: Biological: Durvalumab; Drug: Cisplatin; Drug: Carboplatin; Radiation: external beam radiation therapy (EBRT) + brachytherapy

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: Interventional
• Enrollment (Actual): 770
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Barretos, Brazil, 14784-400
    • Research Site
  • Fortaleza, Brazil, 60336-045
    • Research Site
  • Londrina, Brazil, 86015-520
    • Research Site
  • Porto Alegre, Brazil, 90610-000
    • Research Site
  • Porto Alegre, Brazil, 91350-200
    • Research Site
  • Porto Alegre, Brazil, 90110-270
    • Research Site
  • Porto Alegre, Brazil, 90050-170
    • Research Site
  • Rio de Janeiro, Brazil, 20220-410
    • Research Site
  • Sao Paulo, Brazil, 01246-000
    • Research Site
  • Sao Paulo, Brazil, 01509-900
    • Research Site
  • Sao Paulo, Brazil, 01317-000
    • Research Site
  • São José do Rio Preto, Brazil, 15090-000
    • Research Site
  • São Paulo, Brazil, 03102-002
    • Research Site
• Chile
  • Antofagasta, Chile, 1267348
    • Research Site
  • Santiago, Chile, 7500921
    • Research Site
  • Santiago, Chile, 7630370
    • Research Site
  • Santiago, Chile, 8380455
    • Research Site
  • Temuco, Chile, 4810218
    • Research Site
  • Temuco, Chile, 4810469
    • Research Site
  • Viña del Mar, Chile, 2540488
    • Research Site
• China
  • Changchun, China, 130021
    • Research Site
  • Changsha, China, 410013
    • Research Site
  • Chengdu, China, 610041
    • Research Site
  • Chongqing, China, 400030
    • Research Site
  • Guangzhou, China, 510000
    • Research Site
  • Hangzhou, China, 310022
    • Research Site
  • Hefei, China, 230031
    • Research Site
  • Hefei, China, 230001
    • Research Site
  • Shanghai, China, 200032
    • Research Site
  • Shenyang, China, 110016
    • Research Site
  • Shenyang, China, 100003
    • Research Site
  • Tianjin, China, 300052
    • Research Site
  • Wuhan, China, 430079
    • Research Site
  • Wuhan, China, 430022
    • Research Site
• Hungary
  • Budapest, Hungary, 1122
    • Research Site
  • Debrecen, Hungary, 4032
    • Research Site
  • Győr, Hungary, 9024
    • Research Site
  • Kaposvár, Hungary, 7400
    • Research Site
  • Szeged, Hungary, 6725
    • Research Site
• India
  • Ahmedabad, India, 380015
    • Research Site
  • Gurgaon, India, 122001
    • Research Site
  • Madurai, India, 625107
    • Research Site
  • Mumbai, India, 400012
    • Research Site
  • Nagpur, India, 440026
    • Research Site
  • Nashik, India, 422002
    • Research Site
  • New Delhi, India, 110063
    • Research Site
  • Vishakhapatnam, India, 530017
    • Research Site
• Japan
  • Fukuoka-shi, Japan, 811-1395
    • Research Site
  • Kagoshima-shi, Japan, 890-8520
    • Research Site
  • Koto-ku, Japan, 135-8550
    • Research Site
  • Kyoto-shi, Japan, 606-8507
    • Research Site
  • Nakagami-gun, Japan, 903-0215
    • Research Site
  • Osaka-shi, Japan, 541-8567
    • Research Site
  • Sapporo-shi, Japan, 003-0804
    • Research Site
  • Sendai-shi, Japan, 980-8574
    • Research Site
  • Shinjuku-ku, Japan, 160-8582
    • Research Site
  • Toon-shi, Japan, 791-0295
    • Research Site
  • Yokohama-shi, Japan, 236-0004
    • Research Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 03722
    • Research Site
  • Seoul, Korea, Republic of, 05505
    • Research Site
  • Seoul, Korea, Republic of, 06351
    • Research Site
  • Seoul, Korea, Republic of, 08826
    • Research Site
• Mexico
  • Alc. Cuauhtémoc, Mexico, 06700
    • Research Site
  • Deleg. Tlalpan, Mexico, 14080
    • Research Site
  • Guadalajara, Mexico, 44680
    • Research Site
  • Guadalajara Jalisco, Mexico, 44280
    • Research Site
  • Mérida, Mexico, 97134
    • Research Site
  • San Luis Potosí, Mexico, 78250
    • Research Site
  • Veracruz, Mexico, 91900
    • Research Site
• Peru
  • Lima, Peru, L27
    • Research Site
  • Lima, Peru, LIMA 27
    • Research Site
  • Lima, Peru, LIMA 34
    • Research Site
  • Lima, Peru, LIMA 41
    • Research Site
  • Lima, Peru, LIMA 31
    • Research Site
• Philippines
  • Baguio City, Philippines, 2600
    • Research Site
  • Cebu, Philippines, 6000
    • Research Site
  • Iloilo, Philippines, 5000
    • Research Site
  • Makati, Philippines, 1229
    • Research Site
  • Manila, Philippines, 1015
    • Research Site
  • Quezon City, Philippines, 1112
    • Research Site
• Poland
  • Bialystok, Poland, 15-027
    • Research Site
  • Gdańsk, Poland, 80-214
    • Research Site
  • Gliwice, Poland, 44-101
    • Research Site
  • Lublin, Poland, 20-090
    • Research Site
  • Łódź, Poland, 90-513
    • Research Site
• Russian Federation
  • Arkhangelsk, Russian Federation, 163045
    • Research Site
  • Chelyabinsk, Russian Federation, 454087
    • Research Site
  • Kaluga, Russian Federation, 248007
    • Research Site
  • Moscow, Russian Federation, 115533
    • Research Site
  • Moscow, Russian Federation, 125367
    • Research Site
  • Moscow, Russian Federation, 117997
    • Research Site
  • Novosibirsk, Russian Federation, 630055
    • Research Site
• South Africa
  • Parktown, South Africa, 2193
    • Research Site
  • Port Elizabeth, South Africa, 6045
    • Research Site
• Taiwan
  • Taichung, Taiwan, 40705
    • Research Site
  • Tainan City, Taiwan, 704
    • Research Site
  • Taipei, Taiwan, 10002
    • Research Site
  • Taipei, Taiwan, 10449
    • Research Site
  • Taipei, Taiwan, 11490
    • Research Site
  • Taipei City, Taiwan, 11217
    • Research Site
  • Taoyuan City, Taiwan, 333
    • Research Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Research Site
  • California
    • La Jolla, California, United States, 92093
      • Research Site
    • Orange, California, United States, 92868
      • Research Site
  • Florida
    • Fort Myers, Florida, United States, 33905
      • Research Site
    • Miami, Florida, United States, 33136
      • Research Site
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Research Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Research Site
  • New York
    • Bronx, New York, United States, 10461
      • Research Site
    • Lake Success, New York, United States, 11042
      • Research Site
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Research Site
    • Cleveland, Ohio, United States, 44111
      • Research Site
    • Cleveland, Ohio, United States, 44124
      • Research Site
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Research Site
  • Texas
    • Dallas, Texas, United States, 75390
      • Research Site
    • Dallas, Texas, United States, 75235
      • Research Site
    • Spring, Texas, United States, 77380
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 130 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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	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
Placebo Comparator: Placebo (matching placebo for intravenous infusion); placebo + standard of care concurrent chemoradiation therapy(SoC CCRT)	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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events as assessed by Common Toxicity Criteria for Adverse Events (CTCAE v5.0)	Type, frequency and severity of adverse events (including those from the pre- and post-treatment periods) will be listed according to CTCAE v5.0	Estimated to be up to 2.5 years
The safety and tolerability of durvalumab + SoC CCRT compared to placebo + SoC CCRT as assessed by electrocardiograms (ECGs)	Resting 12-lead ECGs will be assessed by QTcF interval (ms).	Estimated to be up to 2.5 years
The safety and tolerability of durvalumab + SoC CCRT compared to placebo + SoC CCRT as assessed by vital signs(pulse rate) in beats per minute.	Pulse rate will be evaluated according to the schedule of assessments.	Estimated to be up to 2.5 years
The safety and tolerability of durvalumab + SoC CCRT compared to placebo + SoC CCRT as assessed by vital signs(temperature) in degree Celsius.	Temperature will be evaluated according to the schedule of assessments.	Estimated to be up to 2.5 years
The safety and tolerability of durvalumab + SoC CCRT compared to placebo + SoC CCRT as assessed by vital signs(respiration rate) in breaths per minute.	Respiration rate will be evaluated according to the schedule of assessments.	Estimated to be up to 2.5 years
The safety and tolerability of durvalumab + SoC CCRT compared to placebo + SoC CCRT as assessed by vital signs(blood pressure).	Blood pressure will be evaluated according to the schedule of assessments.	Estimated to be up to 2.5 years
The safety and tolerability of durvalumab + SoC CCRT compared to placebo + SoC CCRT as assessed by abnormality in clinical chemistry.	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).	Estimated to be up to 2.5 years
The safety and tolerability of durvalumab + SoC CCRT compared to placebo + SoC CCRT as assessed by abnormality in hematology(cells/L).	Hematology will be assessed by white cell count, platelet count, absolute neutrophil count and absolute lymphocyte count.	Estimated to be up to 2.5 years
The safety and tolerability of durvalumab + SoC CCRT compared to placebo + SoC CCRT as assessed by abnormality in hematology(g/L).	Hematology will be assessed by haemoglobin.	Estimated to be up to 2.5 years

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Urban Scheuring, M.D., Ph.D., AstraZeneca; Principal Investigator: Bradley Monk, M.D, University of Arizona, Arizona, USA

Publications and helpful links

General 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.

Helpful Links

• Related Info
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Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2019
• Primary Completion (Actual): January 20, 2022
• Study Completion (Actual): July 3, 2023

Study Registration Dates

• First Submitted: December 4, 2018
• First Submitted That Met QC Criteria: February 4, 2019
• First Posted (Actual): February 5, 2019

Study Record Updates

• Last Update Posted (Actual): August 1, 2023
• Last Update Submitted That Met QC Criteria: July 28, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Chemoradiotherapy; Durvalumab; Locally Advanced Cervical Cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Uterine Cervical Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Carboplatin; Cisplatin; Durvalumab
• Other Study ID Numbers: D9100C00001; 2018-002872-42 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No