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Study of Effectiveness and Safety of Canakinumab in Adult Subjects With early diagnosed Completely surgically removed Non-small Cell Lung Cancer

Phase 3
Conditions
Health Condition 1: null- completely resected (R0) non -small cell lung cancer (NSCLC)Health Condition 2: C399- Malignant neoplasm of lower respiratory tract, part unspecified
Registration Number
CTRI/2018/06/014392
Lead Sponsor
ovartis Healthcare Pvt Ltd
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Open to Recruitment
Sex
Not specified
Target Recruitment
0
Inclusion Criteria

1. Written informed consent must be obtained prior to any screening

procedures.

2. Age more than 18 years

3. Completely resected (R0) AJCC/UICC v. 8 stage IIA with T less than 4-5 cm

and N0 (no nodal involvement), if no adjuvant chemotherapy is given,

must be randomized within 70 days post complete surgical resection of

their NSCLC.

4. Subjects with completely resected (R0) AJCC/UICC v. 8 stages IIA,

IIB, IIIA or IIIB (T less than 5 cm N2) disease NSCLC, who received

chemotherapy and no radiation therapy must be randomized within

182 days post complete surgical resection of their NSCLC.

5. Subjects with completely resected (R0) AJCC/UICC v. 8 stage IIIA N2

(T less than or equal to 5 cm only) or stage IIIB (Tless than 5cm N2) disease who receive radiation

therapy along with chemotherapy detailed in inclusion criterion 6, must

be randomized within 259 days of complete surgical resection.

6. Adjuvant chemotherapy is mandatory with stage AJCC/UICC v. 8

stage II-IIIA and stage IIIB (T less than 5cm N2) disease for 4 cycles (21 or 28

day cycles) as per local/national guidelines (except if not tolerated, in

which case at least 2 cycles of adjuvant chemotherapy are required).

Adjuvant chemotherapy is mandatory (at least 2 cycles) for all

subjects except those who have stage IIA disease with T(less than 4-5 cm).

Chemotherapy must be cisplatin based. Combination partners may include vinorelbine, etoposide, docetaxel or gemcitabine

for any histology. For non-squamous carcinomas only, the combination partner may be pemetrexed.

7. Subjects must have recovered from all toxicities related to prior

systemic therapy to grade less than or equal to 1 (CTCAE v 4.03). Exception to this criterion: subjects with any grade of alopecia and grade 2 or lessneuropathy are allowed to enter the study.

8. Subjects must have adequate organ function including the following laboratory values at the screening visit:

Absolute neutrophil count (ANC) more than or equal to 1.5 x 109/L

Platelets more than or equal to 100 x 109/L

Hemoglobin (Hgb) more than 9 g/dL

Creatinine clearance greater than 45 ml/min using Cockcroft-Gault formula

Total bilirubin mess than or equal to 1.5 x ULN

Aspartate transaminase (AST) less than or equal to 3 x ULN

Alanine transaminase (ALT) less than or equal 3 x ULN

9. ECOG performance status (PS) of 0 or 1.

10. Willing and able to comply with scheduled visits, treatment plan and

laboratory tests.

Exclusion Criteria

1. Subjects with unresectable or metastatic disease, positive microscopic

margins on the pathology report, and/or gross disease remaining at

the time of surgery.

2. Subjects who received neoadjuvant chemotherapy or neoadjuvant

radiotherapy.

3. Presence or history of a malignant disease, other than the resected

NSCLC, that has been diagnosed and/or required therapy within the

past 3 years. Exceptions to this exclusion include the following:

completely resected basal cell and squamous cell skin cancers, and

completely resected carcinoma in situ of any type.

4. History of interstitial lung disease.

5. History or current diagnosis of cardiac disease, including any of the

following:

recent myocardial infarction or coronary artery bypass graft

(CABG) surgery within last 6 months,

uncontrolled congestive heart failure,

unstable angina (within last 6 months),

clinically significant (symptomatic) cardiac arrhythmias (e.g.,

sustained ventricular tachycardia, and clinically significant second

or third degree AV block without a pacemaker).

6. Thoracic radiotherapy to lung fields � 4 weeks prior to starting cycle 1

day 1 or subjects who have not recovered from radiotherapy-related

toxicities. Radiation therapy is suggested, but not required to be given

to subjects with completely resected (R0) AJCC/UICC v. 8 stage IIIA

or IIIB with T greater than 5cm N2 disease, (mediastinal radiation).

7. Major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic)

within 4 weeks prior to randomization or who have not recovered from

side effects of such procedure. Video-assisted thoracic surgery

(VATS) and mediastinoscopy will not be counted as major surgery and

subjects can be enrolled in the study greater than or equal to 1 week after the procedure.

8. Uncontrolled diabetes as defined by the investigator.

9. Known active or recurrent hepatic disorder including cirrhosis, hepatitis

B and C (positive or indeterminate central laboratory results).

10. Subjects with a history of tuberculosis (TB) infection, active or latent,

or one of the following risk factors:

History of any of the following: residence in a

congregate setting: jail or prison, homeless shelter or

chronic care facility, substance abuse (injected or noninjected);

health care workers with unprotected

exposure to subjects who are at high risk of TB or

subjects with TB disease before identification and

correct airborne precautions of the infected subject.

Close contact (i.e. sharing the same air space in a household or other enclosed environment for

prolonged period (days or weeks, not hours or

Novartis Confidential Page 14

Oncology Protocol (Version No. 00) Protocol No. CACZ885T2301 minutes) with a person with active TB disease within

the past 12 months. Evidence of TB infection, active or latent, at screening

as determined by purified protein derivative (PPD)

skin test and /or QuantiFERON�®-TB Gold (QFT-g)

assay as defined by country guidelines (refer to

Determination of TB status to be further defined in full

protocol).

If presence of TB, active or latent, is

establishe

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
The primary objective is to compare the Diseasefree <br/ ><br>survival (DFS) in the canakinumab versus <br/ ><br>placebo arms as determined by local investigator <br/ ><br>assessment.Timepoint: DFS determined by local investigator assessment
Secondary Outcome Measures
NameTimeMethod
To compare the two treatment groups with respect to lung cancer specific survival (LCSS)Timepoint: time to definitive deterioration in patient-reported outcomes, including key symptom scores, and safety.;To determine whether treatment with canakinumab prolongs OS compared with placebo arm.Timepoint: time to definitive deterioration in patient-reported outcomes, including key symptom scores, and safety.
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