A Clinical Study to know the safety, pharmacokinetics and anticancer activity of NRC-2694-A in patients with advanced cancers

Phase 1

Completed

• Conditions: Neoplasm of unspecified behavior of unspecified site,

• Registration Number: CTRI/2014/01/004293
• Lead Sponsor: NATCO Pharma Limited

Brief Summary

Despite significant advances in systemic therapies, radiation oncology and surgical techniques, many patients with cancer are still incurable. One of the key approaches recently has been to target the receptor tyrosine kinases, which are often over expressed and/or mutated in many tumors and regulate proliferation, apoptosis, angiogenesis, tumor invasiveness and distant metastases. Though several agents have been developed in this area, there is a lot of scope for improvement in terms of newer and better agents.

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Amplified epidermal growth factor receptor (EGFR) signaling is frequently found in human tumors and can be caused by various mechanisms. As amplified EGFR signaling plays an important role in carcinogenesis, inhibiting this process could be the rationale approach in the development of New Chemical Entity (NCE)

NRC-2694-A belongs to the quinazoline class of EGFR tyrosine kinase inhibitor demonstrated good anti cancer activity in preclinical  studies.

Detailed Description

Not available

Study Timeline

• Study Start: 2014-01-13
• Study Completion: 2017-07-02
• Last Update Posted: 2020-06-06

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• •Patients must be greater or equal to 18 years old with expected life expectancy more than 8 weeks.
• •ECOG Performance Score less than or equal to 2 •Patients with evaluable disease, histologically documented confirmed diagnosis of an advanced solid malignancy for whom standard treatment options did not exist •Adequate bone marrow reserve (WBC at least 3,000/mm3, neutrophil count greater than or equal to 2000/mm3, platelet count greater than or equal to 1,00,000mm3 and hemoglobin level 8.0 g/dL), renal function (normal serum creatinine), liver function [total bilirubin level less than or equal to 2 times upper normal limit (UNL) and serum transaminases levels less than or equal to 2.5 times UNL/ less than or equal to 5 times for liver metastasis and/or obstructive jaundice.
• Subjects must have tested negative for, HIV, HbsAg and pregnancy (for female subjects) •Patients must not have received chemotherapy within 14 days (6 weeks for nitrosureas or mytomycin C) 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 2 months after treatment.

Exclusion Criteria

• • Patients with major illness including active cardiac, hepatic, endocrine, renal or psychiatric disorders inadequately controlled with current therapy.
• • Patients with brain metastases or primary CNS malignancies.
• • Concurrent therapy for the cancer (Radiation therapy, chemotherapy etc) • 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 4 hours before or after the study drug administration).

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Adverse events at each dose level will be evaluated using clinical (physical examinations, ECGs and vital signs) and safety laboratory parameters namely Hematology (complete blood count, differential count, platelet count) and Biochemistry values. All adverse events will be graded using National Cancer Institute- Common Terminology Criteria for Adverse Events (NCI-CTCAE)	Adverse events at each dose level will be evaluated using clinical (physical examinations, ECGs and vital signs) and safety laboratory parameters namely Hematology (complete blood count, differential count, platelet count) and Biochemistry values. All adverse events will be graded using National Cancer Institute- Common Terminology Criteria for Adverse Events (NCI-CTCAE)

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetic	Day 1 and Day 12
Tumor Evaluation	Day 30, 60 and 90

Trial Locations

Locations (2)

Nizams Institute of Medical Sciences; 🇮🇳 Hyderabad, ANDHRA PRADESH, India

Tata Memorial Centre; 🇮🇳 (Suburban), MAHARASHTRA, India

Nizams Institute of Medical Sciences

🇮🇳Hyderabad, ANDHRA PRADESH, India

Dr D Raghunadharao

Principal investigator

04023372947

telerama@rediffmail.com