A Phase-I dose escalation study to evaluate Safety of NRC-1111.

Phase 1

Recruiting

• Conditions: 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,

• Registration Number: CTRI/2023/03/051121
• Lead Sponsor: NATCO Pharma Ltd

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2023-03-04
• Last Update Posted: 2024-04-30

Recruitment & Eligibility

• Status: Open to Recruitment
• Sex: All
• Target Recruitment: 26

Inclusion Criteria

• 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.
• Male or female patients aged 18 years or older at the time of consent.
• Patients must have life expectancy ≥ 8 weeks.
• ECOG Performance Score less than or equal to 2.
• 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.
• 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.
• Patients must be willing to practice birth control during and for 6 months after treatment.
• 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.
• 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.
• 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.

Exclusion Criteria

• 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.
• Patients with brain metastases or primary CNS malignancies.
• Radiological confirmation is required for symptomatic patients only.
• Patients receiving concurrent therapy for the cancer (Radiation therapy, chemotherapy).
• 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.
• 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).
• Patients who are pregnant or lactating.
• 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.
• 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).
• Prior treatment with mTOR inhibitors in advanced malignancies.
• Patients who received PI3K inhibitor(s) in any stage of their treatment.
• Patients who tested positive for Coronavirus infection (COVID-19) at the time of enrolment.
• Participation in any clinical study within 60 days before the first dose of Investigational Product.
• Patients who are participating in any other clinical trial (both academic and industry run trials).
• 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.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To determine the safety, tolerability, maximum tolerated dose (MTD) and Dose Limiting Toxicity (DLT) of NRC-1111 tablets when	Day 1, Day 7, Day 14, Day 30, Day 60, Day 90, | Day 120 (EOT) and Day 150 (EOS).
administered orally.	Day 1, Day 7, Day 14, Day 30, Day 60, Day 90, | Day 120 (EOT) and Day 150 (EOS).

Secondary Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (4)

Advanced Centre for Treatment Research and Education in Cancer and Tata Memorial Centre; 🇮🇳 Mumbai, MAHARASHTRA, India

Nizams Institute of Medical Sciences; 🇮🇳 Hyderabad, TELANGANA, India

Sahyadri Super Speciality Hospital; 🇮🇳 Pune, MAHARASHTRA, India

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

Advanced Centre for Treatment Research and Education in Cancer and Tata Memorial Centre

🇮🇳Mumbai, MAHARASHTRA, India

Dr Vikram Gota

Principal investigator

7715019117

vikramgota@gmail.com