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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03057106




Registration number
NCT03057106
Ethics application status
Date submitted
15/02/2017
Date registered
17/02/2017
Date last updated
3/04/2020

Titles & IDs
Public title
Durvalumab and Tremelimumab ± Platinum-Based Chemotherapy in Patients With Metastatic Squamous or Non-Squamous NSCLC
Scientific title
A Randomized Trial of Durvalumab and Tremelimumab ± Platinum-Based Chemotherapy in Patients With Metastatic (Stage IV) Squamous or Non-Squamous Non-Small Cell Lung Cancer (NSCLC)
Secondary ID [1] 0 0
BR34
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lung Cancer Metastatic 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Durvalumab
Treatment: Drugs - Tremelimumab
Treatment: Drugs - Platinum-Based Drug

Active Comparator: Durvalumab and Tremelimumab - Durvalumab q4 weeks until PD + Tremelimumab q 4 wk x 4 doses

Active Comparator: Platinum based chemotherapy + Durvalumab + Tremelimumab - 4 cycles platinum plus gem or pem + Durva + Treme (q 3 wk x 4 cycles)
Followed by:
Squamous Cell: Maintenance Durva q 4 wk until PD Non-Squamous Cell: Pemetrexed + Durva q 4 wk until PD


Treatment: Drugs: Durvalumab
MEDI4736

Treatment: Drugs: Tremelimumab
Tremelimumab

Treatment: Drugs: Platinum-Based Drug
Pemetrexed, cisplatin, carboplatin or gemcitibine

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival - time from randomization to the date of death
Timepoint [1] 0 0
33 months
Secondary outcome [1] 0 0
Progression-free Survival using RECIST 1.1 - time from randomization to the date of the first documented disease progression
Timepoint [1] 0 0
33 months
Secondary outcome [2] 0 0
Objective Response Rate using RECIST 1.1 and iRECIST - proportion of patients with a documented complete response, partial response (CR + PR) based on iRECIST criteria. The primary estimate of ORR will be based on all patients randomized, and compared using Cochran- Mantel-Haeszel test stratified by stratification factors at randomization between the study new treatment and the standard control arms.
Timepoint [2] 0 0
33 months
Secondary outcome [3] 0 0
Number and Severity of Adverse Events - using the NCI Common Terminology Criteria for Adverse Events Version 4.0. A Fisher's exact test will be used to compare adverse events between the study new treatment and the standard control arms if required.
Timepoint [3] 0 0
33 months
Secondary outcome [4] 0 0
Cost Effectiveness of Durvalumab and Tremelimumab concurrently with combination chemotherapy - The mean overall cost per patient for each of the two study treatment arms will be calculated to determine the addition cost per life-year gained.
Timepoint [4] 0 0
33 months
Secondary outcome [5] 0 0
Correlate the expression of correlative markers with outcomes and response
Timepoint [5] 0 0
33 months

Eligibility
Key inclusion criteria
- Patients must have histologically and/or cytologically confirmed diagnosis of squamous
or non-squamous, non-small cell carcinoma of the lung. Patients with poorly
differentiated tumours will only be eligible if NSCLC is confirmed by
immunohistochemistry markers (TTF1/P63 or P40/CK5). Patients with known sensitizing
EGFR mutations or known ALK-fusion are not eligible.

- Patients must have stage IV disease according to the 8th TNM version staging.

- Patients must have an adequate histopathology specimen and must consent to release
this specimen for protocol required testing. This is a mandatory component of the
study.

- Patient must consent to provision of samples of blood in order that the specific
correlative marker assays proscribed may be conducted.

- All patients must have measurable disease as defined by RECIST 1.1 All radiology
studies must be performed within 28 days prior to randomization (within 35 days if
negative).

The criteria for defining measurable disease are as follows:

- CT scan (with slice thickness of 5 mm) = 10 mm --> longest diameter

- Physical exam (using calipers) = 10 mm

- Lymph nodes by CT scan = 15 mm --> measured in short axis

Measurable lesions must be outside a previous radiotherapy field if they are the sole site
of disease, unless disease progression has been documented.

- Patients must be 18 years of age or older.

- ECOG performance status of 0 or 1.

- Absolute neutrophils = 1.5 x 10^9/L

- Platelets = 100 x 10^9/L

- Hemoglobin = 90 g/L

- Bilirubin = 1.5 x UNL (upper limit of normal)

- AST and ALT = 2.5 x UNL (if liver metastases are present, =5 x UNL) Creatinine < 1.25
UNL or Creatinine clearance = 45 mL/min

- Cytotoxic Chemotherapy: Patients may not have received prior cytotoxic chemotherapy
for advanced/metastatic disease.

- Adjuvant Chemotherapy: Patients may have had prior adjuvant therapy for completely
resected disease, providing it has been completed at least 12 months prior to
randomization.

- Patients treated with concurrent chemotherapy/radiation regimens for unresectable
locally advanced Stage III disease will be eligible providing it has been completed at
least 12 months prior to randomization.

- Other Systemic Therapy: Patients may not have received prior EGFR or alk inhibitors.
Patients may not have received prior treatment with immune-based therapy, including
durvalumab and tremelimumab vaccines or oncolytic viral therapy. Patients must have
recovered from any reversible treatment related toxicities prior to randomization.

- Prior external beam radiation is permitted provided a minimum of 14 days (2 weeks)
have elapsed between the last dose of radiation and date of randomization. Concurrent
radiotherapy is not permitted.

Patients must have recovered from any acute toxic effects from radiation prior to
randomization.

- Patients must have recovered from any acute toxic effects from radiation prior to
randomization.

- Surgery: Previous surgery is permitted provided that wound healing has occurred and at
least 14 days have elapsed (major surgery) prior to randomization.

- Patient must be able (i.e. sufficiently fluent) and willing to complete the quality of
life and health economics questionnaires.

- Patient consent must be appropriately obtained in accordance with applicable local and
regulatory requirements.

- Patients must be accessible for treatment and follow-up. All randomized patients must
be followed and treated at participating centres.

- In accordance with CCTG policy, protocol treatment is to begin within 2 working days
of patient randomization.

- Female patients of childbearing potential who are sexually active with a
non-sterilized male partner must use at least one highly effective method of
contraception while on study and for 6 months after the last dose of durvalumab and
tremelimumab or for 3 months after the last dose of durvalumab alone
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Patients with a history of other malignancies, except: adequately treated non-melanoma
skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours
curatively treated with no evidence of disease for = 3 years. Patients with a history
of other malignancies detected at an early stage and whom the investigator believes
have been curatively treated and are at low risk of recurrence MAY be eligible.
Contact CCTG to discuss eligibility prior to enrolling.

- Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease (e.g. colitis or Crohn's disease), diverticulitis with the
exception of diverticulosis, celiac disease or other serious gastrointestinal chronic
conditions associated with diarrhea), systemic lupus erythematosus, Sarcoidosis
syndrome, or Wegener syndrome (granulomatosis with polyangiitis), rheumatoid
arthritis, hypophysitis, uveitis, etc., within the past 3 years prior to the start of
treatment. The following are exceptions to this criterion:

- Patients with alopecia.

- Patients with Grave's disease, vitiligo or psoriasis not requiring systemic
treatment (within the last 2 years).

- Patients with hypothyroidism (e.g. following Hashimoto syndrome) stable on
hormone replacement.

- History of primary immunodeficiency, history of allogenic organ transplant that
requires therapeutic immunosuppression and the use of immunosuppressive agents within
28 days of randomization* or a prior history of severe (grade 3 or 4) immune mediated
toxicity from other immune therapy or grade = 3 infusion reaction.

- Live attenuated vaccination administered within 30 days prior to randomization

- History of hypersensitivity to durvalumab or tremelimumab or any excipient. Patients
who have received other treatment or other antibodies must not have had intolerable
toxicity or required steroids to manage toxicity.

- Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) = 470 msec
in screening ECG measured using standard institutional method or history of familial
long QT syndrome.

- Patients who have untreated and/or uncontrolled cardiovascular conditions and/or have
symptomatic cardiac dysfunction (unstable angina, congestive heart failure, myocardial
infarction within the previous year or cardiac ventricular arrhythmias requiring
medication, history of 2nd or 3rd degree atrioventricular conduction defects).
Patients with a significant cardiac history, even if now controlled, should have a
LVEF = 45%. (Note: patients with uncomplicated controlled hypertension do not require
LVEF measurement in the absence of other significant cardiac history)

- Concurrent treatment with other investigational drugs or anti-cancer therapy

- Patients with untreated brain or meningeal metastases are not eligible. Patients with
treated CNS disease who have radiologic AND clinical evidence of stable brain
metastases, with no evidence of cavitation or hemorrhage in the brain lesion, are
eligible providing that they are asymptomatic and do not require corticosteroids (must
have discontinued steroids at least 1 week prior to randomization).

- Pregnant or Lactating Women: Women of childbearing potential must have a pregnancy
test (urine or serum) proven negative within 14 days prior to randomization. If urine
test is positive, pregnancy testing may then include an ultrasound to rule-out
pregnancy if a false-positive is suspected. For example, when beta-human chorionic
gonadotropin is high and partner is vasectomized, it may be associated with tumour
production of hCG, as seen with some cancers. Patient will be considered eligible if
an ultrasound is negative for pregnancy. Men and women of child-bearing potential must
agree to use adequate contraception.

- Patients with serious illnesses or medical conditions which would not permit the
patient to be managed according to the protocol (including corticosteroid
administration), or would put the patient at risk. This includes but is not limited
to:

- Contraindications to the use of pemetrexed, gemcitabine, cisplatin and/or
carboplatin (consult product monograph);

- History of significant neurologic or psychiatric disorder which would impair the
ability to obtain consent or limit compliance with study requirements;

- Active infection requiring systemic therapy; (including any patient known to have
active hepatitis B, hepatitis C or human immunodeficiency virus (HIV) or
tuberculosis);

- Active peptic ulcer disease or gastritis;

- Known pneumonitis or pulmonary fibrosis with clinically significant impairment of
pulmonary function.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,TAS,VIC,WA
Recruitment hospital [1] 0 0
Campbelltown Hospital - Campbelltown
Recruitment hospital [2] 0 0
Coffs Habour Health Campus - NCCI - Coffs Harbour
Recruitment hospital [3] 0 0
Concord Repatriation General Hospital - Concord
Recruitment hospital [4] 0 0
Nepean Hospital - Kingswood
Recruitment hospital [5] 0 0
St. George Hospital, Cancer Care Centre - Kogarah
Recruitment hospital [6] 0 0
The Tweed Hospital - Lismore
Recruitment hospital [7] 0 0
Liverpool Cancer Therapy Centre, Liverpool Hospital - Liverpool
Recruitment hospital [8] 0 0
Prince of Wales Hospital - Randwick
Recruitment hospital [9] 0 0
Princess Alexandra Hospital - Brisbane
Recruitment hospital [10] 0 0
The Prince Charles Hospital - Chermside
Recruitment hospital [11] 0 0
Mater Research Institute South Brisbane - South Brisbane
Recruitment hospital [12] 0 0
Gold Coast University Hospital - Southport
Recruitment hospital [13] 0 0
Toowoomba Hospital - Toowoomba
Recruitment hospital [14] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [15] 0 0
Ballarat Health Services - Ballarat
Recruitment hospital [16] 0 0
Epworth HealthCare - Richmond - Richmond
Recruitment hospital [17] 0 0
Border Medical Oncology - Wodonga
Recruitment hospital [18] 0 0
Saint John of God Hospital Subiaco - Subiaco
Recruitment hospital [19] 0 0
St. Vincent's Hospital - Victoria Park
Recruitment postcode(s) [1] 0 0
2560 - Campbelltown
Recruitment postcode(s) [2] 0 0
2450 - Coffs Harbour
Recruitment postcode(s) [3] 0 0
2139 - Concord
Recruitment postcode(s) [4] 0 0
2751 - Kingswood
Recruitment postcode(s) [5] 0 0
2217 - Kogarah
Recruitment postcode(s) [6] 0 0
2480 - Lismore
Recruitment postcode(s) [7] 0 0
2170 - Liverpool
Recruitment postcode(s) [8] 0 0
2031 - Randwick
Recruitment postcode(s) [9] 0 0
4102 - Brisbane
Recruitment postcode(s) [10] 0 0
4032 - Chermside
Recruitment postcode(s) [11] 0 0
4101 - South Brisbane
Recruitment postcode(s) [12] 0 0
4215 - Southport
Recruitment postcode(s) [13] 0 0
4350 - Toowoomba
Recruitment postcode(s) [14] 0 0
7000 - Hobart
Recruitment postcode(s) [15] 0 0
3350 - Ballarat
Recruitment postcode(s) [16] 0 0
3121 - Richmond
Recruitment postcode(s) [17] 0 0
3690 - Wodonga
Recruitment postcode(s) [18] 0 0
6008 - Subiaco
Recruitment postcode(s) [19] 0 0
3065 - Victoria Park
Recruitment outside Australia
Country [1] 0 0
Canada
State/province [1] 0 0
Alberta
Country [2] 0 0
Canada
State/province [2] 0 0
British Columbia
Country [3] 0 0
Canada
State/province [3] 0 0
New Brunswick
Country [4] 0 0
Canada
State/province [4] 0 0
Ontario
Country [5] 0 0
Canada
State/province [5] 0 0
Prince Edward Island
Country [6] 0 0
Canada
State/province [6] 0 0
Quebec
Country [7] 0 0
Canada
State/province [7] 0 0
Saskatchewan

Funding & Sponsors
Primary sponsor type
Other
Name
Canadian Cancer Trials Group
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
AstraZeneca
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
National Health and Medical Research Council, Australia
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Durvalumab is a new type of drug for many kinds of cancer. It is considered "immunotherapy"
and not "chemotherapy". Laboratory tests show that it works by allowing the immune system to
detect cancer and reactivate the immune response. This may help to slow down the growth of
cancer or may cause cancer cells to die. Durvalumab has been shown to shrink tumours in
animals and has been studied in more than 5000 people and seems promising.

Tremelimumab is a new type of drug for various types of cancers. It works in a similar way to
durvalumab and may improve the effect of durvalumab. Tremelimumab may also help slow the
growth of the cancer cells or may cause cancer cells to die. It has been shown to shrink
tumours in animals and has been studied in over 1200 people and seems promising.
Trial website
https://clinicaltrials.gov/show/NCT03057106
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Natasha Leighl
Address 0 0
Princess Margaret Hospital, Toronto, ON Canada
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications