CTRI/2017/12/010781 [Registered on: 06/12/2017] Trial Registered Prospectively
Last Modified On:
23/09/2019
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group, Active Controlled Trial
Public Title of Study
A Clinical Trial to Assess the Effectiveness of Lupins LNP3794 drug alone or in Combination with Docetaxel, in Patients with RAS Mutation Positive Advanced Non-Small Cell Lung Cancer
Scientific Title of Study
A Phase II/III Pivotal, Open-label, Randomized, 3 Arm Study to Assess the Efficacy of LNP3794 Monotherapy or in Combination with Docetaxel, Compared with Docetaxel Alone, in Patients with RAS Mutation Positive Locally Advanced and Metastatic Non-Small Cell Lung Cancer
Trial Acronym
NA
Secondary IDs if Any
Secondary ID
Identifier
LRP/LNP3794/2016/006
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Opp. Mahamarg Bus Stop, Mumbai Naka, Nashik-422004, MAHARASHTRA Nashik MAHARASHTRA
9823061929
drraj@cmccnasik.in
Dr Chirag Desai
Hemato Oncology Clinic Ahmedabad Pvt. Ltd.
1st Floor, Vedanta Institute of Medical Sciences, Near Samved Hospital, Stadium Commerce College Road, Navrangpura-380009, Ahmedabad, GUJARAT Ahmadabad GUJARAT
9824047561
chiragdesai.oncology@gmail.com
Dr Pratap K Das
Indraprastha Apollo Hospital
Department of Medical Oncology, Ground Floor, OPD, Sarita Vihar, Delhi Mathura Road, New Delhi 110076
DELHI New Delhi DELHI
1-8-31/1, Minister Rd, Krishna Nagar Colony,
Begumpet, Secunderabad- 500003, Telangana, INDIA
9849822904
sambasvims@gmail.com
Dr Nalini Kilara
M S Ramaiah Medical College and Hospitals
Dept. of Medical Oncology, M S Ramaiah Nagar, MSRIT Post, Bangalore-560054, KARNATAKA Bangalore KARNATAKA
9845089492
nalini_kilara@yahoo.com
Dr Rakesh Reddy
Mahatma Gandhi Cancer Hospital and Research Institute
Room no.104, Dept of surgical Oncology, Mahatma Gandhi Cancer Hospital and Research Institute (A Unit of Vizag Hospital and Cancer Research Centre Private Limited) 1/7, M.V.P. Colony, Visakhapatnam-530 017, Andhra Pradesh, India Visakhapatnam ANDHRA PRADESH
9013355935
drrakeshreddyboya@yahoo.com
Dr Poonam Patil
Manipal Hospital
Dept of Oncology, 98, HAL Airport Road- Bangalore 560 017, KARNATAKA Bangalore KARNATAKA
9945687185
poonampatil@manipalhospitals.com
Dr Anand Pathak
Meditrina Institute of Medical Sciences
278, Central Bazar Road, Ramdaspeth, Nagpur, Maharashtra 440012 Nagpur MAHARASHTRA
7126669666
jueely1194@yahoo.co.in
Dr Manikam Prabagar
N. G. Hospital Pvt. Ltd.
No. 577, Trichy Road, Near B-5 Police Station, Singanallur, Coimbatore, Tamilnadu - 641005 Coimbatore TAMIL NADU
Department of Radiation Oncology, P.O Box No 2417, Medical College Campus, Thiruvanthapuram 695011, Kerala Thiruvananthapuram KERALA
9447882149
sivanandancd@hotmail.com
Dr Tushar Vishvasrao Patil
Sahyadri Speciality Hopsital
Plot No 30 C, Karve Road Main Road, Karve Road Deccan, Near Tilak Tank Oposite To Garware College Near Erandawane, Pune - 411004, Maharashtra Pune MAHARASHTRA
09552522556
tussipats@hotmail.com
Dr Shailesh Bondarde
Shatabdi Super Speciality Hospital
Cabin No. 4, 1st Floor, G-11, Suyojit City Centre, Opp Mahamarg Bus Stand, Mumbai Naka, Nashik 422005, MAHARASHTRA Nashik MAHARASHTRA
2532501888
shaileshbondarde@yahoo.com
Dr Shyam Aggarwal
Sir Ganga Ram Hospital
Room no 212 A, Department of Oncology, Rajinder Nagar-11060, New Delhi, DELHI New Delhi DELHI
9811075870
drshyam_aggarwal@yahoo.com
Dr Rakesh Neve
Sterling Hospital
Sector 27, Near Bhel Chowk, Pradhikaran, Nigdi, Near Mouli Garden, Pimpri-Chinchwad,Pune 411044 Pune MAHARASHTRA
9881143140
rakesh.neve23@gmail.com
Dr Kumar Prabhash
Tata Memorial Hospital
Dept. of Oncology, Dr. Ernest Borges Marg Parel-400 012 Mumbai, MAHARASHTRA Mumbai MAHARASHTRA
09224182898
kprabhash1@gmail.com
Dr Unmesh Takalkar
United CIIGMA Institute of Medical Sciences Pvt Ltd
1.Patients of either gender (≥ 18 years) with locally advanced or metastatic NSCLC that has progressed after standard treatment, which must have included platinum-doublet chemotherapy and/or a programmed cell death protein 1 [PD 1]/programmed cell death protein ligand 1 [PD-L1] inhibitors
2.Patients with a histologically or cytologically confirmed diagnosis of locally advanced or metastatic Stage IIIB or Stage IV NSCLC
3.Confirmed activating RAS mutational status based on circulating tumor deoxyribose nucleic acid (ctDNA) as determined by the central testing laboratory
4.Failure of anti-cancer therapy (as provided in inclusion criteria no. 1) based on a history of radiological documentation of disease progression in advanced disease or subsequent relapse of the disease
5.Patients with measurable disease, i.e., presenting with at least one measurable tumor lesion as per RECIST v1.1
6.Patients with an ECOG performance status score of ≤ 2
7.Patients must be able to swallow and retain orally administered medication and not have any clinically significant gastrointestinal abnormalities that may alter absorption
8.Patients must have clinical laboratory values that meet the following criteria:
a.Absolute neutrophil count ≥ 1.5 × 109/L
b.Platelets ≥ 100 × 109/L
c.Hemoglobin ≥ 8 g/dL
d.Liver function tests:
i.Serum bilirubin ≤ 1.2 x upper limit of normal (ULN)
ii.AST and ALT ≤ 3 x ULN without liver metastases or ≤ 5 × ULN if the patient has documented liver metastases
iii.International normalized ratio (INR) < 1.3 if the patient is not on anticoagulants or < 3 if the patient is on anticoagulants
e.Serum creatinine ≤ 1.5 mg/dL or estimated glomerular filtration rate > 40 mL/min/1.73 m2
f.Serum amylase ≤ 1.5 × ULN
g.Serum lipase ≤ 1.5 × ULN
9.Patients must have adequate life expectancy in the opinion of the Investigator
10.Acute toxicities from any prior therapy, surgery, or radiotherapy must have resolved to Grade 0 or 1 as per the National Cancer Institute Common terminology criteria for adverse events version 4.03 (NCI-CTCAE v4.03)
11.Women of childbearing potential must have a negative serum pregnancy test prior to study entry and agree to use highly effective methods of contraception to prevent pregnancy from study entry through at least 3 months after the last dose of the study medication (such contraception may include hormonal birth control e.g., combined estrogen and progestogen containing [oral, intravaginal, or transdermal] or progesterone only [oral, injectable, or implantable] hormonal contraception associated with inhibition of ovulation, intrauterine devices, intrauterine hormone releasing system OR bilateral tubal occlusion, vasectomized partner, or sexual abstinence)
12.A female patient of non-childbearing potential will have had at least 12 continuous months of natural (spontaneous) amenorrhea, follicle stimulating hormone (FSH) level > 40 mIU/mL at Screening, or have had surgical bilateral oophorectomy, hysterectomy, or tubal ligation > 6 weeks prior to Screening; in the case of oophorectomy alone, reproductive status will be confirmed by hormone level assessment
13.A male patient must agree to use adequate contraception from study entry through at least 3 months after the last dose of study medication
14.Patients must be willing to undergo and able to tolerate frequent magnetic resonance imaging (MRI) or computed tomography (CT) assessments during the study
15.Patients must be able to understand and be willing to complete symptom assessments using a PRO instrument
16.Patients must be able to understand and be willing to voluntary provide signed and dated written informed consent
17.Patients willing and able to comply with the requirements of the protocol.
ExclusionCriteria
Details
1. Patients with central nervous system metastases as confirmed by CT/MRI of brain
2. Patients with a history of another primary malignancy, with the exception of locally excised non-melanoma skin cancer and carcinoma in situ of the uterine cervix. A patient who has had no evidence of disease from another primary cancer for 5 or more years is allowed to participate in the study
3. Patients with any serious and/or unstable pre-existing medical disorder (aside from malignancy exception above), psychiatric disorder, seizure disorder, or other conditions that could interfere with the patient’s safety, providing informed consent or compliance to the study procedures, in the opinion of the Investigator
4. Patients with a known immediate or delayed hypersensitivity reaction or idiosyncrasy to LNP3794, docetaxel or its excipients
5. Patients with a history of treatment with MEK inhibitors (such as selumetinib, trametinib, and sorafenib), BRAF inhibitors (such as dabrafenib, vemurafenib) or docetaxel as monotherapy or as part of a combination regimen or study regimen (Note: prior treatment with paclitaxel is acceptable)
6. Anti-cancer therapy (including chemotherapy and radiation therapy) within the last 3 weeks prior to randomization or limited field of radiation for palliation within 7 days of the first dose of study medication
7. Patients who have any contraindication for therapy with docetaxel
8. Patients who have a history or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy; for example predisposing factors of RVO or central serous retinopathy include uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes
10. Patients who have any severe and/or uncontrolled medical conditions or other conditions that, in the opinion of the Investigator, could affect the patient’s participation in the study
11. Patients who have liver disease such as cirrhosis, decompensated liver disease, chronic active hepatitis, or chronic persistent hepatitis
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Not Applicable
Blinding/Masking
Not Applicable
Primary Outcome
Outcome
TimePoints
To evaluate the progression free survival (PFS) in the treatment arms in the target population.
12 months
Secondary Outcome
Outcome
TimePoints
•To examine measures of efficacy, including overall survival (OS), objective response rate (ORR), duration of response (DOR), and best overall response (BOR) in the target population.
To evaluate measures of safety and tolerability for patients in the study.
To evaluate LNP3794 pharmacokinetics (PK) in a subset of LNP3794 and LNP3794 - docetaxel treated patients.
Total Sample Size="141" Sample Size from India="141" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
This is a Phase II/III, pivotal, 3 arm, randomized, multi-center, open label, parallel group study in NSCLC patients who are positive for RAS mutations (KRAS, NRAS or HRAS).The study will evaluate the efficacy, safety, tolerability, PK and PD of LNP3794 administered alone or in combination with docetaxel compared to docetaxel alone.
Due to poor accrual rate and because of negligible incidence of RAS mutation positive NSCLC patients encountered in the study Lupin decided to terminate the study.