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CTRI Number  CTRI/2019/04/018479 [Registered on: 08/04/2019] Trial Registered Prospectively
Last Modified On: 28/05/2020
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group, Placebo Controlled Trial 
Public Title of Study   Study of Durvalumab or Placebo given along with Chemoradiation therapy in women with Locally Advanced Cervical Cancer 
Scientific Title of Study   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 (CALLA)  
Trial Acronym  CALLA 
Secondary IDs if Any  
Secondary ID  Identifier 
D9100C00001 Version 1 dated 02 Oct 2018  Protocol Number 
NCT03830866  ClinicalTrials.gov 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name   
Designation   
Affiliation   
Address 




 
Phone    
Fax    
Email    
 
Details of Contact Person
Scientific Query
 
Name  Mr Tapankumar M Shah 
Designation  SMM - Director 
Affiliation  AstraZeneca Pharma India Ltd. 
Address  AstraZeneca Pharma India Ltd. Block N1, 12th Floor, Manyata Embassy Business Park Rachenahalli, Outer Ring Road, Bangalore KARNATAKA 560045 India Bangalore KARNATAKA 560045 India

Bangalore
KARNATAKA
560045
India 
Phone  91-9535104975  
Fax  91-8067748857  
Email  tapankumar.shah@astrazeneca.com  
 
Details of Contact Person
Public Query
 
Name  Mr Tapankumar M Shah 
Designation  SMM - Director 
Affiliation  AstraZeneca Pharma India Ltd. 
Address  AstraZeneca Pharma India Ltd. Block N1, 12th Floor, Manyata Embassy Business Park Rachenahalli, Outer Ring Road, Bangalore KARNATAKA 560045 India Bangalore KARNATAKA 560045 India

Bangalore
KARNATAKA
560045
India 
Phone  91-9535104975  
Fax  91-8067748857  
Email  tapankumar.shah@astrazeneca.com  
 
Source of Monetary or Material Support  
AstraZeneca AB 151 85 Södertälje Sweden 
 
Primary Sponsor  
Name  AstraZeneca AB 
Address  151 85 Sodertalje Sweden 
Type of Sponsor  Pharmaceutical industry-Global 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     Brazil
Chile
China
Hungary
India
Japan
Mexico
Peru
Philippines
Poland
Russian Federation
South Africa
Taiwan
United States of America  
Sites of Study
Modification(s)  
No of Sites = 10  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Samit Purohit  Action Cancer Hospital  A 4 Paschim Vihar New Delhi
New Delhi
DELHI 
9873726472

samitmedonc@gmail.com 
Dr Hari Goyal  Artemis Hospitals  Artemis Hospitals Sector 51 Gurgaon 122001 Haryana Gurgaon India
Gurgaon
HARYANA 
9111246767999

hari.g@artemishospitals.com 
Dr M Nagarajan  G Kuppuswamy Naidu Memorial Hospital  Dept. of Medical Oncology Post Box No. 6327, Nethaji Road, Pappanaickenpalayam, PIN-641037
Coimbatore
TAMIL NADU 
9894016715

mnr81@yahoo.com 
Dr Shruti Kate  HCG Manavta Cancer Center  HCG Manavta Cancer Center Behind shivang Auto Mumbai Naka Nasik 422002 Maharashtra India
Nashik
MAHARASHTRA 
917506117343

drshruti@mcrinasik.com 
Dr Ajay Mehta   HCG NCHRI Cancer Centre  HCG NCHRI Cancer Centre 50 and 51 Mouja Wanjari Bande Nawaz Nagar Near Automotive Square Kalamana Ring Road Nagpur 440026 Maharashtra India
Nagpur
MAHARASHTRA 
919823190192

drajay.mehta@hcgoncology.com 
Dr Rakesh Reddy  Mahatma Gandhi Cancer Hospital and Research Institute  Mahatma Gandhi Cancer Hospital and Research Institute 1 7 MVP Colony Vishakapatnam 530017 Andhra Pradesh India
Visakhapatnam
ANDHRA PRADESH 
917702086187

drrakeshreddyboya@yahoo.com 
Dr Kirushnakumar Subramanian  Meenakshi Mission Hospital and Research Centre  Lake Area Melur Road Madurai 625107
Madurai
TAMIL NADU 
04524263000

drkskk@yahoo.com 
Dr Bhavesh Parekh  Shalby Hospital  Shalby Cancer and Research Institute Opposite Karnavati Club S G Road
Ahmadabad
GUJARAT 
9825034353

bhaveshdm1@hotmail.com 
Dr Sudeep Gupta  Tata Memorial Hospital  Dept. of Medical Oncology Dr. E. Borges Marg, Parel, PIN-400 012
Mumbai
MAHARASHTRA 
9821298642

sudeepgupta04@yahoo.com 
Dr Amit Jain   Valentis Cancer Hospital   Department of Medical Oncology, Mussoorie, Mawana Road
Meerut
UTTAR PRADESH 
919410816252

dramit2001@gmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 10  
Name of Committee  Approval Status 
Action Cancer Hospital Ethics Committee  Approved 
Artemis Health Sciences Institutional Ethics Committee  Approved 
Ethics Committee Shalby Limited  Approved 
HCG NCHRI Cancer Centre Central Ethics Committee  Approved 
Institutional Ethics committee Meenakshi Mission Hospital and Research Centre  Approved 
Institutional Ethics Committee TATA Memorial Hospital  Approved 
Institutional Ethics Committee Valentis Cancer Hospital  Approved 
Institutional Ethics Committee, G. KUPPUSWAMY NAIDU MEMORIAL HOSPITAL  Approved 
Mahatma Gandhi Cancer Hospital and Research Institute IEC   Approved 
Manavata Clinical Research Institute Ethics Committee  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  , C539||Malignant neoplasm of cervix uteri, unspecified,  
 
Intervention / Comparator Agent
Modification(s)  
Type  Name  Details 
Intervention  Durvalumab  Patients will be in a 1:1 ratio to either Durvalumab plus SOC CRT or Placebo plus SoC CRT.  
Comparator Agent  Placebo  Placebo as consolidation treatment Dose 1000 ml of Saline Solution for infusion Frequency once in 28 days Route of administration Intravenous Duration of therapy is 2 years 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  99.00 Year(s)
Gender  Female 
Details  Patients are eligible to be included in the study only if all of the following inclusion criteria
and none of the exclusion criteria apply:

Informed consent

1 Capability of giving signed informed consent which includes compliance with the
requirements and restrictions listed in the informed consent form (ICF) and in this
protocol

2 Provision of signed and dated written informed consent form prior to any
mandatory study specific procedures sampling and analyses

3 Provision of signed and dated written genetic informed consent prior to collection
of sample for genetic analysis

4 Females age more than equal to 18 years at the time of screening

5 Histologically confirmed cervical adenocarcinoma cervical squamous carcinoma
or cervical adenosquamous carcinoma and the following requirements

 FIGO Stages IB2 to IIB node positive N more than equal to 1 OR FIGO Stages IIIA to IVA
with any N stage N more than equal to 0
 Nodal staging may be either surgical or by imaging RECIST v1.1
 No evidence of metastatic disease M0

6 World Health Organization (WHO)/ECOG performance status (PS) of 0 or 1 at enrollment and randomization

7 At least 1 lesion not previously irradiated that qualifies as a RECIST 1.1 TL at
baseline

Tumor assessment by CT scan or MRI must be performed within 28 days
prior to randomization

8 Suitability and fitness for CCRT as determined by the Investigator

9 Adequate organ and marrow function as defined below
 Hemoglobin more than equal to 9.0 g per dL
 Absolute neutrophil count more than equal to 1.5 × 109 per L
 Platelet count more than equal to 75 × 109 per L
 Serum bilirubin less than equal to 1.5 × the upper limit of normal ULN. This will not apply to
patients with confirmed Gilberts syndrome who will be allowed in consultation with their physician and AstraZeneca
Alanine aminotransferase and aspartate aminotransferase less than equal to 2.5 × ULN
 Creatine clearance (CrCl) more than equal to 60 mL per min calculated by Cockcroft-Gault equation

10 Life expectancy of at least 12 weeks

11 Body weight more than 30 kg

12 Female 
 
ExclusionCriteria 
Details  1 Diagnosis of small cell neuroendocrine histology cervical cancer

2 Intent to administer a fertility-sparing treatment regimen

3 Evidence of metastatic disease per RECIST 1.1 including lymph nodes more than equal to 15 mm
short axis above the L1 cephalad body or outside the planned radiation field

4 Patients who have undergone a previous hysterectomy including a supracervical
hysterectomy or will have a hysterectomy as part of their initial cervical cancer
therapy

5 History of allogeneic organ transplantation

6 Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn’s disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome,
or Wegener syndrome [granulomatosis with polyangiitis, Graves’ disease,
rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to
this criterion:
a Patients with vitiligo or alopecia
b Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement
c Patients with any chronic skin condition that does not require systemic therapy
 d Patients without active disease in the last 5 years may be included but only after
consultation with the Study Physician
e Patients with celiac disease controlled by diet alone

7 Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, active ILD, serious chronic GI conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of
incurring AEs or compromise the ability of the patient to give written informed consent

8 History of another primary malignancy except for
a Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence

bAdequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease

c Adequately treated carcinoma in situ without evidence of disease

9 History of active primary immunodeficiency

10 Active infection including tuberculosis (clinical evaluation that includes clinical
history, physical examination and radiographic findings, and tuberculosis testing in
line with local practice), hepatitis B (known positive HBV HBsAg result),
hepatitis C (HCV), or human immunodeficiency virus (positive HIV 1/2
antibodies). Patients with a past or resolved HBV infection (defined as the presence
of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible.
Patients positive for HCV antibody are eligible only if polymerase chain reaction
(PCR) is negative for HCV RNA.

11 Brain metastases or spinal cord compression. Patients with suspected brain metastases at screening should have an MRI (preferred) or CT each preferably with IV contrast of the brain prior to study entry. Brain metastases will not be recorded as RECIST TLs at baseline.

12 Mean QT interval corrected for heart rate using Fridericias formula more than equal to 470 ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart)

13 Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients

14 Prior history of vesicovaginal, colovaginal, or rectovaginal fistula

15 Prior chemotherapy or radiation therapy for the management of cervical cancer

16 Exposure to immune-mediated therapy prior to the study for any indication including, but not limited to, other anti CTLA-4, anti-PD-1, anti-PD-L1, and anti-PD-L2 antibodies, or therapeutic anticancer vaccines

17 Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (eg, hormone replacement therapy) is acceptable.

18 Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine while receiving IP and up to 30 days after the last dose of IP

19 Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.

20 Current or prior use of immunosuppressive medication within 14 days before the
first dose of durvalumab.

21 Participation in another clinical study with an investigational product (IP) administered in the last 28 days

22 Previous IP assignment in the present study

23 Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study

24 Prior randomization or treatment in a previous durvalumab clinical study regardless of treatment arm assignment

25 Female patients who are pregnant or breastfeeding or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of study treatment

26 Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements

27 Genetics research study (optional)
Exclusion criteria for participation in the optional (DNA) genetics research component of the study include:

a Previous allogeneic bone marrow transplant
b Non-leukocyte-depleted whole blood transfusion in 120 days of genetic sample collection 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Not Applicable 
Blinding/Masking   Double Blind Double Dummy 
Primary Outcome  
Outcome  TimePoints 
To assess the efficacy of durvalumab and SoC
CCRT compared with placebo and SoC CCRT in
terms of PFS 
PFS: Time from date of randomization until
tumor progression or death due to any cause 
 
Secondary Outcome  
Outcome  TimePoints 
To further assess the efficacy of durvalumab and
SoC CCRT compared with placebo and SoC
CCRT in terms of OS (key), PFS in PD-L1
positive patients, ORR, CR rate, and DoR in
Patients with CR 
Overall Survival (OS) (Time-frame approximately 4 years)

Progression Free Survival (PFS) (Time-frame approximately 4 years)

Overall Response Rate (ORR) (Time-frame approximately 4 years)

Complete Response Rate (CR) (Time-frame approximately 4 years)

Duration of Response: DoR in Patients with CR: DoR in Patients with CR 
To assess disease related symptoms and HRQoL
in patients with cervical cancer treated with
durvalumab and SoC CCRT compared with
placebo and SoC CCRT using the EORTC QLQC30
and CX24 
Change from baseline in EORTC QLQ C30 and EORTC CX24
2 years 
To assess the PK of durvalumab when in
combination with CCRT 
Up to Disease Progression. (approximately 4 years)  
To investigate the immunogenicity of
durvalumab when in combination with CCRT 
Up to Disease Progression. (approximately 4 years)  
To assess the safety and tolerability profile of
durvalumab and SoC CCRT compared to placebo
and SoC CCRT 
Overall Survival (approximately 6 years)  
To further assess the efficacy of durvalumab and
SoC CCRT compared with placebo and SoC
CCRT in terms of PFS (3 yr) 
Progression Free Survival PFS at 3 years.  
 
Target Sample Size   Total Sample Size="714"
Sample Size from India="55" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   Phase 3 
Date of First Enrollment (India)   18/04/2019 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  15/02/2019 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="4"
Months="6"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  
Open to Recruitment 
Recruitment Status of Trial (India)  Open to Recruitment 
Publication Details   None yet 
Brief Summary
Modification(s)  

This is a randomized, double-blind, placebo controlled, multi-center, global, Phase III study to determine the efficacy and safety of durvalumab when combined with SoC CCRT and administered as maintenance therapy following SoC CCRT compared to placebo with SoC CCRT as systemic treatment in patients with FIGO Stages IB2 to IVA cervical cancer. In order to be eligible for this study, patients must be ≥18 years of age with FIGO Stages IB2 to IIB N+ and IIIA to IVA with any N. Patients must not have previously received any definitive surgical, radiation, or systemic therapy for cervical cancer and must be immunotherapy-naïve.

Approximately 714 patients from multiple sites will be randomised 1:1 to receive either Durvalumab or placebo for 24 doses. Patients in both the arms will receive SoC CCRT consisting of EBRT + Brachytherapy, and concurrent cisplatin or carboplatin. A 6th week of platinum agent can be given per investigator discretion

Patients will receive their assigned treatment until completion of planned therapy, clinical progression or RECIST 1.1-defined radiological progression or histopathologic progression on biopsy unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation criteria is met.

Following completion of SoC CCRT, patients will be evaluated by clinical and radiological assessment. During the first 3 years (164) after randomization, this assessment will include an interval history for new signs or symptoms, targeted physical examination to evaluate for local progression, and imaging (CT or MRI) per RECIST 1.1 or histopathologic assessment q12w. During Years 4, and 5, imaging/histopathologic assessments will be performed q24w and then annually until a PFS endpoint has been met or closure of the study.

 
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