Malignant solid tumour
Conditions
Interventions
Patients will receive 80 mg/m2 of tinostamustine administered over 1 hour on
Day 1 and 15 of each 4-week treatment cycle.
Sponsors
Mundipharma
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: General Inclusion Criteria: • Signed informed consent. • Patients age >=18 years at signing of the informed consent. • Life expectancy > 3 months • Histologically confirmed diagnosis of advanced or metastatic solid tumors, disease should have progressed following at least 1 line of therapy and no other standard therapy with proven clinical benefit is available or recommended based on the investigator*s individual risk- benefit assessment for the patient. • Patients with secondary metastasis to the central nervous system (CNS) are eligible if they have had brain metastases resected or have received radiation therapy ending at least 4 weeks prior to trial day 1 and they meet all of the following criteria: (1) Residual neurological symptoms 1,000 µL. • Platelets >=100,000 / µL. Platelet transfusions within the 14 days before Day 1 of Cycle 1 is prohibited. • Aspartate aminotransferase/alanine aminotransferase (AST/ALT)
Exclusion criteria
Exclusion criteria: To be eligible to participate in the trial, a patient cannot meet any of the following exclusion criteria: • Patients with primary CNS cancer. • Patients with QTc interval (Fridericia*s formula) >450 ms. • Patients who are on treatment with drugs known to prolong the QT/QTc interval. Refer to CredibleMeds list of drugs with known risk of Torsade des pointes (TdP): http://crediblemeds.org/new-drug-list. • Patients who are being treated with valproic acid for any of its indication (epilepsy, mood disorder) • Any serious medical condition that interferes with adherence to trial procedures. • Prior history of another solid tumor malignancy diagnosed within the last 3 years of trial enrollment excluding adequately treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer, in situ breast cancer, in situ prostate cancer (patients must have shown no evidence of active disease for 2 years prior to enrollment). • Pregnant or breast feeding women. • New York Heart Association (NYHA) stage III/IV congestive heart failure (Section 13.2). The following arrhythmias: atrial fibrillation/flutter with poor rate control, documented sustained ventricular tachycardia (defined as >30 seconds or requiring cardioversion before 30 seconds have elapsed) or TdP. • Significant co-morbidities (e.g., active infection requiring systemic therapy, history of human immunodeficiency virus [HIV] infection, or active Hepatitis B or Hepatitis C). • Use of other investigational agents or previous anticancer therapies within 28 days prior to the first dose of tinostamustine, provided the patient has recovered from any related toxicities >=Grade 1. • Steroid treatment within 7 days prior to trial treatment. Patients that require intermittent use of bronchodilators, topical steroids, or local steroid injections will not be excluded from the trial. Patients who have been stabilized to 10 mg prednisolone orally (PO) once daily (QD) (or equivalent), daily (or less) at least 7 days prior to trial drug administration are allowed. Cohort-specific eligibility criteria phase 2 portion of the trial in addition to the general inclusion/exclusion criteria for listed above (refer to protocol page 19-21). Cohort 1 Patient Population: Relapsed/Refractory Small-cell Lung Cancer (SCLC) Cohort 2 Patient Population: Relapsed/Refractory Soft Tissue Sarcoma Cohort 3 Patient Population: Relapsed/Refractory Triple Negative Breast Cancer (RECRUITMENT INTO THIS COHORT HAS NOW BEEN HALTED) Cohort 4 Patient Population: Relapsed/Refractory Ovarian Cancer Cohort 5 Patient Population: Relapsed/Refractory Endometrial Cancer (RECRUITMENT INTO THIS COHORT HAS NOW BEEN HALTED)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase 2: Evaluation of Toxicity and Response Rate in Selected Solid Tumor Cohorts • To determine the objective response rate (ORR) [complete response (CR) plus partial response (PR)] of any duration, plus the rate of patients with stable disease (SD) of at least 4 months duration at a dose of 80 mg/m2 administered over 1 hour on Day 1 and 15 of each 4-week treatment cycle. | — |
Secondary
| Measure | Time frame |
|---|---|
| Phase 2: Evaluation of Toxicity and Response Rate in Selected Solid Tumor Cohorts • To evaluate safety and tolerability of 80 mg/m2 of tinostamustine administered over 1 hour on Day 1 and 15 of each 4-week treatment cycle. • To determine the progression-free survival (PFS) time for patients who received 80 mg/m2 of tinostamustine administered over 1 hour on Day 1 and 15 of each 4-week treatment cycle. • To determine the overall survival (OS) for patients who received 80 mg/m2 of tinostamustine administered over 1 hour on Day 1 and 15 of each 4-week treatment cycle. • To determine duration of response. • To establish the trough PK profiles of tinostamustine. Exploratory Objective • To correlate the extent of gene expression changes in tumor samples with anti-tumor activity. | — |
Countries
Netherlands
Outcome results
None listed