CTRI/2023/03/051121 [Registered on: 28/03/2023] Trial Registered Prospectively
Last Modified On:
30/04/2024
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Single Arm Study
Public Title of Study
A Phase-I dose escalation study to evaluate Safety of NRC-1111.
Scientific Title of Study
A Phase-I, multicenter, open-label, dose escalation study of NRC-1111 in adult patients with advanced solid malignancies.
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
NAT11P1, Version 3.0, Date: September 21, 2022
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Sadashivudu Gundeti
Designation
Professor & Head - Department of Medical Oncology
Affiliation
Nizams Institute of Medical Sciences
Address
Punjagutta, Hyderabad, Telangana 500082,India Medical Oncology Block, 2nd floor
Hyderabad TELANGANA 500082 India
Phone
9440911865
Fax
Email
drssgundeti@yahoo.com
Details of Contact Person Scientific Query
Name
Dr Atul Gupta
Designation
Vice President-Medical & Scientific Affairs Medical & Scientific Affairs
Affiliation
Navitas Lifesciences Pvt. Limited
Address
Mobius Towers, SJR i Park, EPIP, Whitefield, Bangalore, India. Mobius Towers, SJR i Park, EPIP, Whitefield, Ground Floor, Tower 1. Bangalore KARNATAKA 560066 India
Phone
08043515700
Fax
Email
atul.gupta@navitaslifesciences.com
Details of Contact Person Public Query
Name
Thirumalaivasan K
Designation
Assistant Vice President - Clinical Development Operations
Affiliation
Navitas Lifesciences Pvt. Limited
Address
Mobius Towers, SJR i Park, EPIP, Whitefield, Bangalore, India. Mobius Towers, SJR i Park, EPIP, Whitefield, Ground Floor, Tower 1. Bangalore KARNATAKA 560066 India
NATCO House, Road No. 2, Banjara Hills, Hyderabad – 500034
Type of Sponsor
Pharmaceutical industry-Indian
Details of Secondary Sponsor
Name
Address
NIL
NIL
Countries of Recruitment
India
Sites of Study
No of Sites = 4
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Vikram Gota
Advanced Centre for Treatment Research and Education in Cancer and Tata Memorial Centre
Room No. 102, Clinical pharmacology laboratory, Khanolkar Shodhika building,
Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Sector 22, Kharghar,
Navi Mumbai-410210.
Mumbai MAHARASHTRA
7715019117
vikramgota@gmail.com
Dr Sadashivudu Gundeti
Nizams Institute of Medical Sciences
Department of Medical Oncology, Panjagutta Rd, Panjagutta Market, Punjagutta, Hyderabad, Telangana 500082,India Hyderabad TELANGANA
Tata Memorial Centre Institutional Ethics Committee - 3 (ACTREC)
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: C348||Malignant neoplasm of overlappingsites of bronchus and lung, (2) ICD-10 Condition: C508||Malignant neoplasm of overlappingsites of breast, (3) ICD-10 Condition: C108||Malignant neoplasm of overlappingsites of oropharynx, (4) ICD-10 Condition: C569||Malignant neoplasm of unspecifiedovary,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
Not Applicable
Not Applicable
Intervention
NRC-1111
Dose: 5 mg, 10 mg, 25 mg, 50 mg and 100 mg
Route of Administration and frequency: Oral route and once daily.
Intervention Duration: 120 days
Inclusion Criteria
Age From
18.00 Year(s)
Age To
75.00 Year(s)
Gender
Both
Details
Patients will be considered eligible for the study based on the following criteria:
1. Patients willing and able to provide voluntary written informed consent and to follow the protocol requirements.
2. Male or female patients aged 18 years or older at the time of consent.
3. Patients must have life expectancy ≥ 8 weeks.
4. ECOG Performance Score less than or equal to 2.
5. Patients with histologically documented, confirmed diagnosis of an advanced solid
malignancy for whom standard treatment options do not exist. Tumours must have
progressed (RECIST v1.1) on the last line of therapy before enrolment into the study.
6. Patients must have measurable lesion per RECIST v1.1.
8. Patients must not have received chemotherapy within 30 days and radiotherapy within
3 weeks and must not have undergone surgery within 2 weeks before dosing.
9. Patients must be willing to practice birth control during and for 6 months after
treatment.
10. Negative urine pregnancy test within 72 hours before starting study treatment in all premenopausal
women (PMS) and woman with < 12 months after onset of menopause.
This test is not required for women who have undergone hysterectomy and sterilization.
11. Women of childbearing potential, (defined as women physiologically capable of becoming pregnant) they must agree to use effective method of contraception during dosing and for at least 06 months after the treatment discontinuation) practicing
two acceptable methods of contraception.
12. Male patients must agree to use a condom.
• Patient is non-fertile (orchiectomy) or has a female partner
of nonchildbearing potential (i.e., postmenopausal,
surgically sterile).
• Patient and his female partner must agree to use an
adequate contraceptive method throughout the study
period and for 6 months following the last dose of
investigational product.
• Male patient engaged in sexual activity with a pregnant
female is required to use a condom throughout the study
period and for 6 months following the last dose of
investigational product.
Acceptable methods of contraception include the following:
• Intrauterine devices plus condoms
• Double-barrier methods (e.g., condoms and diaphragms with spermicidal gel or foam)
• Hormonal contraceptives (oral, depot, patch, injectable, or
vaginal ring), stabilized for at least 30 days prior to the
screening visit, plus condoms. Note: If the patient becomes
sexually active during the study, she should use one of the
other acceptable methods noted above in addition to the hormonal contraceptive until it has been stabilized for 30 days.
ExclusionCriteria
Details
Patients meeting any of the following criteria will be excluded from the study:
1. Has a major illness, including active cardiac, hepatic, endocrine, pulmonary, autoimmune disease, interstitial lung disease, renal or psychiatric disorders, inadequately controlled with therapy corresponding to the illness.
2. Patients with brain metastases or primary CNS
malignancies. Radiological confirmation is required for symptomatic patients only.
3. Patients receiving concurrent therapy for the cancer (Radiation therapy, chemotherapy).
4. Has tested positive for HIV, HBsAg, HCV antibody, or HCV RNA at screening. However, patients who test positive for HCV antibody, but negative for HCV RNA, will be allowed. In addition, patients with controlled HIV, chronic HBV on suppressive antiviral therapy, or a history
of HCV infection status post-curative antiviral treatment
with an HCV viral load below limit of quantification are permitted to participate.
5. Has baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >480 milliseconds [CTCAE Grade 1] using Fredericia’s QT correction formula).
6. Patients who are pregnant or lactating.
7. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study, and which may obscure the evaluation of toxicity or alters drug
metabolism.
8. Impairment of gastrointestinal function that could significantly alter the absorption of the study drug and also the use of medication altering gastric pH (mild antacids are permitted if taken either 2 hours before or after the study drug administration).
9. Prior treatment with mTOR inhibitors in advanced malignancies.
10. Patients who received PI3K inhibitor(s) in any stage of their treatment.
11. Patients who tested positive for Coronavirus infection (COVID-19) at the time of enrolment.
12. Participation in any clinical study within 60 days before the first dose of Investigational Product.
13. Patients who are participating in any other clinical trial (both academic and industry run trials).
14. Patients with clinically manifest diabetes mellitus (treated and/or with clinical signs or with fasting glucose > 140 mg/dL or 7.8 mmol/L, HbA1c > 5.7), history of gestational diabetes mellitus or documented steroid induced diabetes mellitus.
Method of Generating Random Sequence
Not Applicable
Method of Concealment
Not Applicable
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To determine the safety, tolerability, maximum tolerated dose (MTD) and Dose Limiting Toxicity (DLT) of NRC-1111 tablets when
administered orally.
Day 1, Day 7, Day 14, Day 30, Day 60, Day 90,
Day 120 (EOT) and Day 150 (EOS).
Secondary Outcome
Outcome
TimePoints
To evaluate the anticancer activity of NRC-1111 in patients with advanced solid malignancies.
Screening Visit, Day 1, Day 30, Day 60, Day 90 and Day 120 (EOT).
To evaluate the single and multiple dose pharmacokinetics of NRC-1111 in patients with advanced solid malignancies.
Serial PK samples will be collected on Day 1 and Day 7 at pre dose, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 24.0 hours from dosing.
Target Sample Size
Total Sample Size="26" Sample Size from India="26" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
The study will be conducted in patients with confirmed diagnosis of advanced solid malignancies for whom standard treatment options do not exist. The primary objective of the study is to determine the safety, tolerability, maximum tolerated dose (MTD) and Dose Limiting Toxicity (DLT) of NRC-1111 tablets when administered orally. The secondary objective is to evaluate the anticancer activity, single and multiple dose pharmacokinetics of NRC-1111 in patients with advanced solid malignancies.