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

Phase 3

Completed

• Conditions: Malignant neoplasm of lower respiratory tract, part unspecified,

• Registration Number: CTRI/2018/06/014392
• Lead Sponsor: Novartis Healthcare Pvt Ltd

Brief Summary

**A phase III, multicenter, randomized, double blind, placebo controlled study evaluating the efficacy and safety of canakinumab versus placebo as adjuvant therapy in adult subjects with stages AJCC/UICC v. 8 II-IIIA and IIIB (T5cm N2) completely resected (R0) non-small cell lung cancer (NSCLC)**

target sample size for India is 40 patients

FPFV will be in May 2018

Detailed Description

Not available

Study Timeline

• Study Start: 2018-06-15
• Study Completion: 2022-09-22
• Last Update Posted: 2024-08-27

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 1500

Inclusion Criteria

• Written informed consent must be obtained prior to any screening procedures.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• Willing and able to comply with scheduled visits, treatment plan and laboratory tests.

Exclusion Criteria

• Subjects with unresectable or metastatic disease, positive microscopic margins on the pathology report, and/or gross disease remaining at the time of surgery.
• Subjects who received neoadjuvant chemotherapy or neoadjuvant radiotherapy.
• 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.
• History of interstitial lung disease.
• 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).
• 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).
• 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.
• Uncontrolled diabetes as defined by the investigator.
• Known active or recurrent hepatic disorder including cirrhosis, hepatitis B and C (positive or indeterminate central laboratory results).
• 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 established then treatment for TB (according to country guidelines for TB treatment or TB treatment must be completed before treatment with immunomodulating drugs) must have been completed prior to screening as per country guidelines.
• In the absence of country TB (active or latent) guidelines, the following has been demonstrated: TB has been adequately treated with antibiotics, cure can be demonstrated, and risk factors resulting in TB exposure and contracting TB have been removed (e.g. subject no longer lives in highrisk TB exposure setting).
• Those with any other medical condition, which in the opinion of the investigator places the subject at an unacceptable risk for participation in immunomodulatory therapy Those requiring systemic or local treatment with any immune modulating agent in doses with systemic effects e.g. high dose oral of intravenous steroids (>20 mg prednisone orally daily for >14 days, > 5 mg prednisone orally daily or the equivalent dose of intravenous steroid or methotrexate >15 mg weekly.
• Live vaccination within 3 months prior to first dose of study drug.
• Prior treatment with canakinumab or drugs of a similar mechanism of action (IL-1beta inhibitor).
• History of hypersensitivity to canakinumab or drugs of a similar class.
• Subjects who have received an investigational drug or device within 30 days prior to first dose of study drug or those who are expected to participate in any other investigational drug or device during the conduct of the study.
• Subjects receiving any biologic drugs targeting the immune system (for example, TNF blockers, anakinra, rituximab, abatacept, or tocilizumab).
• Any medical condition resulting in a life expectancy of less than 5 years, other than the risk for recurrent lung cancer.
• Pregnant or nursing women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test 19.
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 130 days(approximately five terminal half-lives) after stopping medication.
• Highly effective contraception methods include: Total abstinence (when this is in line with the preferred and usual lifestyle of the subject.
• Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks before taking study treatment.
• In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment Male sterilization (at least 6 months prior to screening).
• The vasectomized male partner should be the sole partner for that subject Use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device or intrauterine system or other forms of hormonal contraception that have comparable efficacy (failure rate less than 1 percent), for example hormone vaginal ring or transdermal hormone contraception.
• In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment.
• Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (i.e. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy with or without hysterectomy, total hysterectomy, or tubal ligation at least six weeks ago.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
survival (DFS) in the canakinumab versus	DFS determined by local investigator assessment
The primary objective is to compare the Diseasefree	DFS determined by local investigator assessment
placebo arms as determined by local investigator	DFS determined by local investigator assessment
assessment.	DFS determined by local investigator assessment

Secondary Outcome Measures

Name	Time	Method
To determine whether treatment with canakinumab prolongs OS compared with placebo arm.	time to definitive deterioration in patient-reported outcomes, including key symptom scores, and safety.
To compare the two treatment groups with respect to lung cancer specific survival (LCSS)	time to definitive deterioration in patient-reported outcomes, including key symptom scores, and safety.

Trial Locations

Locations (7)

Asian Institute of Oncology Pvt. Ltd; 🇮🇳 Mumbai, MAHARASHTRA, India

HCG Manavata Cancer; 🇮🇳 Nashik, MAHARASHTRA, India

Healthcare Global Enterprises Limited,; 🇮🇳 Bangalore, KARNATAKA, India

Mumbai Oncocare Centre; 🇮🇳 Mumbai, MAHARASHTRA, India

Rajiv Gandhi Cancer Institute and Research Centre; 🇮🇳 Delhi, DELHI, India

Tata Medical Center; 🇮🇳 Kolkata, WEST BENGAL, India

Tata Memorial Hospital; 🇮🇳 Mumbai, MAHARASHTRA, India

Asian Institute of Oncology Pvt. Ltd

🇮🇳Mumbai, MAHARASHTRA, India

Dr Ramakant Deshpande

Principal investigator

9820422222

r.deshpande@acicancer.com