Clinical trial NCT03830866: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Locally Advanced Cervical Cancer
Keywords: Durvalumab
Chemoradiotherapy
Locally Advanced Cervical Cancer
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2019-02-05
Enrollment: 770
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Progression-free Survival (PFS) Based on the Investigator Assessment According to RECIST 1.1 or Histopathologic Confirmation of Local Tumour Progression
timeFrame: 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 outcomes:
measure: 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%
timeFrame: 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
measure: Overall Survival (Count)
timeFrame: 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
measure: Overall Survival (Duration)
timeFrame: 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
measure: Objective Response Rate (ORR)
timeFrame: 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
measure: Complete Response Rate
timeFrame: 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
measure: Duration of Response (DoR) in Patients With Complete Response (CR)
timeFrame: 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 outcomes:
Locations:
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: La Jolla
country: United States
facility: Research Site
state: California
city: Orange
country: United States
facility: Research Site
state: California
city: Fort Myers
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Augusta
country: United States
facility: Research Site
state: Georgia
city: Ann Arbor
country: United States
facility: Research Site
state: Michigan
city: Bronx
country: United States
facility: Research Site
state: New York
city: Lake Success
country: United States
facility: Research Site
state: New York
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Spring
country: United States
facility: Research Site
state: Texas
city: Barretos
country: Brazil
facility: Research Site
city: Fortaleza
country: Brazil
facility: Research Site
city: Londrina
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Rio de Janeiro
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: São José do Rio Preto
country: Brazil
facility: Research Site
city: São Paulo
country: Brazil
facility: Research Site
city: São Paulo
country: Brazil
facility: Research Site
city: Antofagasta
country: Chile
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Temuco
country: Chile
facility: Research Site
city: Temuco
country: Chile
facility: Research Site
city: Viña del Mar
country: Chile
facility: Research Site
city: Changchun
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Chongqing
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Hefei
country: China
facility: Research Site
city: Hefei
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shenyang
country: China
facility: Research Site
city: Shenyang
country: China
facility: Research Site
city: Tianjin
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Debrecen
country: Hungary
facility: Research Site
city: Győr
country: Hungary
facility: Research Site
city: Kaposvár
country: Hungary
facility: Research Site
city: Szeged
country: Hungary
facility: Research Site
city: Ahmedabad
country: India
facility: Research Site
city: Gurgaon
country: India
facility: Research Site
city: Madurai
country: India
facility: Research Site
city: Mumbai
country: India
facility: Research Site
city: Nagpur
country: India
facility: Research Site
city: Nashik
country: India
facility: Research Site
city: New Delhi
country: India
facility: Research Site
city: Vishakhapatnam
country: India
facility: Research Site
city: Fukuoka-shi
country: Japan
facility: Research Site
city: Kagoshima-shi
country: Japan
facility: Research Site
city: Koto-ku
country: Japan
facility: Research Site
city: Kyoto-shi
country: Japan
facility: Research Site
city: Nakagami-gun
country: Japan
facility: Research Site
city: Osaka-shi
country: Japan
facility: Research Site
city: Sapporo-shi
country: Japan
facility: Research Site
city: Sendai-shi
country: Japan
facility: Research Site
city: Shinjuku-ku
country: Japan
facility: Research Site
city: Toon-shi
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Alc. Cuauhtémoc
country: Mexico
facility: Research Site
city: Deleg. Tlalpan
country: Mexico
facility: Research Site
city: Guadalajara Jalisco
country: Mexico
facility: Research Site
city: Guadalajara
country: Mexico
facility: Research Site
city: Mérida
country: Mexico
facility: Research Site
city: San Luis Potosí
country: Mexico
facility: Research Site
city: Veracruz
country: Mexico
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Baguio City
country: Philippines
facility: Research Site
city: Cebu
country: Philippines
facility: Research Site
city: Iloilo
country: Philippines
facility: Research Site
city: Makati
country: Philippines
facility: Research Site
city: Manila
country: Philippines
facility: Research Site
city: Quezon City
country: Philippines
facility: Research Site
city: Bialystok
country: Poland
facility: Research Site
city: Gdańsk
country: Poland
facility: Research Site
city: Gliwice
country: Poland
facility: Research Site
city: Lublin
country: Poland
facility: Research Site
city: Łódź
country: Poland
facility: Research Site
city: Arkhangelsk
country: Russian Federation
facility: Research Site
city: Chelyabinsk
country: Russian Federation
facility: Research Site
city: Kaluga
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Novosibirsk
country: Russian Federation
facility: Research Site
city: Parktown
country: South Africa
facility: Research Site
city: Port Elizabeth
country: South Africa
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Tainan City
country: Taiwan
facility: Research Site
city: Taipei City
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan City
country: Taiwan
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: Urban Scheuring, M.D., Ph.D.
role: STUDY_DIRECTOR
affiliation: University of Arizona, Arizona, USA
name: Bradley Monk, M.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.