CTRI/2024/01/061635 [Registered on: 19/01/2024] Trial Registered Prospectively
Last Modified On:
29/09/2025
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Single Arm Study
Public Title of Study
A clinical trial to study the safety and effectiveness of Tenalisib in patients with advanced breast cancers
Scientific Title of Study
A Phase II, Multi-center, Single-arm, Open-label Study to Assess the Efficacy and Safety of Tenalisib, a PI3K δ/γ, and SIK3 Inhibitor, in Patients with Metastatic Triple Negative Breast Cancer (TNBC)
Ground floor, Oncology building, Lake Area, Melur Road, Madurai,
Tamilnadu 625107, India.
Madurai TAMIL NADU
7904423513
drsajusv@gmail.com
Dr Ashish Joshi
Mumbai Oncocare Centre
PI OPD no 2, 2nd Floor, Mumbai Oncocare Centre (Unit of Cellcure Cancer Centre Pvt. Ltd.) 2nd Floor,Majithia Apartments, God’s Gift Premises Co-op. society Ltd, S V Road, Irla, Vile Parle (W), 400056 Mumbai (Suburban) MAHARASHTRA
9167009042
ashjoshi44@mocindia.co.in
Dr SadaShivudu
Nizams Institute of Medical Sciences
2nd floor, Department of Medical oncology,
Nizams Institute of Medical Sciences, Punjagutta,
Hyderabad, Telangana, India, 500082. Hyderabad TELANGANA
9440911865
drssgundeti@yahoo.com
Dr Minish Mahendra Jain
Noble Hospitals Private Limited
153, Magarpatta City Road,
Hadapsar, Pune - 411013,
Maharashtra Pune MAHARASHTRA
9823133390
minishjain009@gmail.com
Dr Vivek Agarwala
Rabindranath Tagore International Institute of Cardiac Sciences
Premises No 1489 (124),
Mukundapur, E. M. Bypass, Kolkata - 700099. Kolkata WEST BENGAL
8879222875
drvivekagarwala@gmail.com
Dr Tushar Vishvasrao Patil
Sahyadri Super speciality Hospitals Pvt. Ltd
First Floor, Dr. Tushar Patils OPD, Plot no 30- C, Erandvane, Karve road, Deccan Gym Khana, Pune, Maharashtra- 411004 Pune MAHARASHTRA
9552522556
tussipats@hotmail.com
Dr Sudeep Gupta
Tata Memorial Centre
1109, 11th Floor Homi Bhabha Block, Dr. Ernest Borges Marg, Parel (E), Mumbai-400012 Mumbai MAHARASHTRA
1. Female patients who provide informed consent prior to any study-specific procedures.
2. Patients must be ≥18 years of age, at the time of signing informed consent.
3. Female patients who have histologically confirmed TNBC, defined as having ≤1% cellular expression of ER and PR as determined by immunohistochemistry (IHC), and HER2 expression of 0 to 1+ by IHC, or 2+ by IHC and fluorescence in situ hybridization (FISH) negative, according to American Society of Clinical Oncology (ASCO)/ College of American Pathologists (CAP) guidelines.
4. Patients who have received at least 1 but not more than 3 prior chemotherapy regimens in a metastatic setting.
5. Patients with at least one measurable lesion, per RECIST version 1.1 at baseline (i.e., lesion ≥10 mm in the longest diameter; lymph nodes ≥15 mm in short axis) that can be accurately assessed by CT scan or MRI and is suitable for repeated assessment at follow-up visits. Bone-only disease is not permitted.
6. ECOG performance status 0 to 2.
7. Life expectancy of at least 3 months.
8. Adequate bone marrow, liver, and renal functions as assessed within 7 (±2) days before the first dose of the study drug as defined below: a. Hemoglobin ≥ 9.0 g/dL (shouldn’t be transfused or treated with erythropoietin to maintain or exceed this level).
b. Absolute neutrophil count (ANC) ≥ 1.0 x 109/L without growth factor support.
c. Platelet count ≥ 150 x 109/L.
d. Total bilirubin ≤ 1.5 times the ULN (or ≤ 3 x ULN, if the patient has Gilbert syndrome).
e. ALT and AST ≤ 3 x ULN (≤ 5 x ULN for patients with liver metastasis or liver involvement).
f. Creatinine clearance ≥ 30 mL/min (calculated using the Cockcroft-Gault formula) for patients with creatinine levels above ULN.
9. Female patients of childbearing potential should be willing to use a medically acceptable method of contraception while participating in the study and for 30 days after the last dose of the study drug AND must have a negative serum pregnancy test within 72 hours prior to Cycle 1 Day 1 (C1D1).
10. Ability to swallow and retain oral medication.
11. Willingness and capability to comply with the study requirements.
ExclusionCriteria
Details
1. Patients receiving anticancer therapy (e.g., chemotherapy, biologic therapy, or any other investigational product) within 4 weeks or 5 half-lives of the drug prior to C1D1, whichever is shorter.
2. Patient who has not recovered from acute toxicities (defined as NCI-CTCAE grade > 1) of previous therapy except treatment-related alopecia. (Note: Patients with any unresolved toxicities which in the opinion of PI are stable and controlled with medication can be enrolled in the study).
3. Prior exposure to PI3K inhibitors (e.g., alpelisib, buparlisib) for breast cancer.
4. Major surgery within 4 weeks of starting study treatment OR any patient who has not recovered from the effects of major surgery.
5. Patient with symptomatic uncontrolled brain metastasis. (Note: A scan to confirm the absence of brain metastases is not required. Patients whose brain metastatic disease has remained stable for ≥ 4 weeks (prior to the start of study treatment) following treatment of brain metastases are eligible. The patient can receive a stable dose of corticosteroids before and during the study if steroids were started at least 4 weeks prior to C1D1).
6. HIV-positive patients who are on antiretroviral therapy OR active hepatitis C OR active hepatitis B virus infections. (Note: Documentation of infection HIV, HBV, and HCV will be done based on medical history).
7. Ongoing immunosuppressive therapy including systemic corticosteroids except as allowed per concomitant medication.
8. Known history of severe liver injury (e.g., alcoholic liver disease, primary biliary cirrhosis, ongoing extrahepatic obstruction caused by stones, cirrhosis of the liver or portal hypertension) as judged by the investigator. (Note: Exception will be patients with liver metastasis who can be enrolled in the study).
9. History of severe cutaneous reactions [e.g., Drug Rash with Eosinophilia and Systemic Symptoms (DRESS), Stevens-Johnson syndrome (SJS), or Toxic Epidermal Necrolysis (TEN)] in the past.
10. Active gastrointestinal tract disease with malabsorption syndrome or uncontrolled inflammatory gastrointestinal diseases such as Crohn’s disease or ulcerative colitis, as judged by the investigator.
11. Myocardial infarction within 6 months before starting therapy, symptomatic congestive heart failure (New York Heart Association > Class II), unstable angina, or unstable cardiac arrhythmia requiring medication or clinically relevant findings in the ECG such as second-or third-degree AV block, significant prolongation of the QTcF interval, unless agreed between the investigator and the medical monitor.
12. Concurrent disease or condition that would interfere with study participation or safety, such as the following:
a. Active, clinically significant infection requiring a parenteral antimicrobial agent.
b. Clinically significant bleeding diathesis or coagulopathy, including known platelet function disorder.
c. Mood disorders like OCD, severe depression, history of suicidal attempts, schizophrenia, etc. as per the investigator’s discretion
13. Concurrent medications or substances with the potential to affect the activity or pharmacokinetics of tenalisib, as reviewed and confirmed by a medical monitor.
14. Pregnancy or lactation.
15. Patients with other active malignancies at the time of screening except for adequately treated in situ carcinoma of the cervix uteri or basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin. (Note: Patients with prior malignancies which are treated and are in remission without requiring active treatment are allowed in the study.)
16. A serious uncontrolled medical disorder or active infection which would impair the ability of the patient to receive study treatment or whose control may be jeopardized by the complications of this therapy.
Method of Generating Random Sequence
Not Applicable
Method of Concealment
Not Applicable
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
Efficacy-
a. Clinical benefit rate (CBR) defined as the percentage of patients achieving complete response (CR), partial response (PR), or stable disease (SD) for 16 weeks or longer based on Response Evaluation Criteria in Solid Tumor (RECIST) 1.1 on treatment
b. Duration of Clinical Benefit (DoCB).
c. Overall Response Rate (ORR), & Duration of Response (DoR).
d. Progression Free Survival (PFS).
Safety- To evaluate & grade Adverse Events (AEs), grade 3/4 AEs, & Serious Adverse Events (SAEs), using NCI-CTCAE Version 5.0.
Radiological assessment by RECIST version 1.1 at C3D1 (± 7 days) & approximately 8 weeks thereafter (± 7 days), and/ or at the EOT, & as clinically indicated (if clinical progression is suspected).
Secondary Outcome
Outcome
TimePoints
Pharmacokinetics-Trough plasma concentrations of tenalisib & its metabolite (IN0385).
Exploratory- Correlation of efficacy to baseline mutational status (PIK3CA, AKT1, PTEN, TP53, INPP4B, BRCA1, and BRCA2).
Pharmacokinetics-PK assessment pre-dose on C1D15, C2D1, C2D15, & C3D1.
Exploratory-Mutational status at baseline
Target Sample Size
Total Sample Size="40" Sample Size from India="40" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
The objective of this Phase II, open-label, single-arm, study, is to evaluate the efficacy and safety of tenalisib in 40 patients with metastatic TNBC, who have received at least one but not more than 3 prior therapies in a metastatic setting.
Tenalisib at the dose of 400 mg BID will be administered orally in 28 days of the cycle until disease progression, consent withdrawal, or unacceptable toxicity