• Cohort 1: Relapsed/refractory Small Cell Lung Cancer • Cohort 2: Relapsed/refractory Soft Tissue Sarcoma • Cohort 3: Relapsed/refractory Triple-Negative Breast Cancer • Cohort 4: Relapsed/refractory ovarian cancer • Cohort 5: Relapsed/refractory endometrial cancer On 05 March 2021 the Sponsor has taken the decision to halt recruitment into the Cohorts for relapsed/refractory triple-negative breast cancer (TNBC) and relapsed/refractory endometrial cancer on this study. MedDRA versio
Conditions
Interventions
Product Name: Tinostamustine
Product Code: EDO-S101
Pharmaceutical Form: Lyophilisate for solution for infusion
INN or Proposed INN: TINOSTAMUSTINE
Current Sponsor code: EDO S101
Concentration unit: m
Sponsors
Mundipharma Research Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Patient willing and able to sign the 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 • 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 = Grade 1 (2) No glucocorticoids requirement or patients may be receiving low doses of glucocorticoids providing the dose has been stable for at least 2 weeks prior to starting the trial medication (3) Follow-up imaging studies show no progression of treated lesions and no new lesions • Evaluable disease; measurable on imaging as assessed by RECIST version 1.1 • ECOG performance status =2 • ANC (polymorphonuclear [PMN] cells plus bands) >1,000/µL • Platelets =100,000/µL. . Platelet transfusions within the 14 days before Day 1 of Cycle 1 is prohibited. • AST/ALT =3× upper limit of normal (ULN). In cases with liver involvement ALT/ AST =5× ULN • Total bilirubin =1.5 mg/dL unless elevated due to known Gilbert’s syndrome • Creatinine =1.5 ULN • Serum potassium and magnesium at least at the lowest limit of normal (LLN) range, before every IMP administration. If it is below LLN, supplementation is permissible • Female study participants of child-bearing potential and their partners, and male study participants who intend to be sexually active with a woman of child-bearing potential, must be willing to use at least TWO highly effective forms of contraception Cohort 1: • Histologically or cytologically confirmed limited or extensive disease stage of SCLC • Received at least 1 line of prior combination chemotherapy or biological therapy and no other standard therapy with proven clinical benefit is available/recommended • At least 28 days should have elapsed since prior treatment as long as the patient has recovered from any related toxicities • Prior radiotherapy is acceptable the patient has recovered from any radiotherapy related acute toxicities • The disease progressing during/relapsing after the previous treatment • Presence of measurable disease as defined by RECIST version 1.1 Cohort 2: • Histologically confirmed diagnosis of advanced, unresectable, or metastatic STS not amenable to curative treatment • Received at least 1 prior line chemotherapy or biological therapy regimen and no other standard therapy with proven clinical benefit is available or recommended. At least 28 days should have elapsed since prior chemotherapy as long as the patient recovered from any related toxicities • Disease progressing during or relapsing after the previous treatment • Presence of measurable disease as defined by RECIST version 1.1 Cohort 3: RECRUITMENT INTO THIS COHORT HAS NOW BEEN HALTED Cohort 4: • Histologically or cytologically confirmed advanced ovarian cancer epithelial ovarian cancer including primary peritoneal cancer or fallopian tube cancer • At least 28 days should have elapsed since prior chemotherapy • Disease progressing during or relapsing after the previous treatment • Presence of measurable disease as defined by RECIST version 1.1 Cohort 5: RECRUITMENT INTO THIS COHORT HAS NOW BEEN HALTED Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64
Exclusion criteria
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 • Patients who are being treated with Valproic Acid for any 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 breastfeeding 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 IMP administration are allowed
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluation of Response Rate in Selected Solid Tumor Cohorts. The Primary Objective of this study is 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 Objective: The Secondary Objectives of this study are: 1) 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. 2) 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. 3) 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. 4) To determine duration of response. 5) To establish the whole PK profiles of Tinostamustine. The Exploratory Objective is to correlate the extent of gene expression changes in tumor samples with anti-tumor activity.;Primary end point(s): Phase 2 is designed to determine the ORR plus the rate of patients with SD of at least 4 months duration of the RP2D (80 mg/m2 of tinostamustine administered over 1 hour on Day 1 and 15 of each 4-week treatment cycle).;Timepoint(s) of evaluation of this end point: Tumor response assessment by imaging will be performed at baseline and every 2 cycles during treatment and every 2 months after stopping treatment according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The Secondary Objectives of this study are: 1) 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 2) 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 3) 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 4) To determine duration of response 5) To establish the whole PK profiles of Tinostamustine The Exploratory Objective is to correlate the extent of gene expression changes in tumor samples with anti-tumor activity.;Timepoint(s) of evaluation of this end point: Safety evaluations will be performed at each study visit i.e. D1 and D15 of each treatment cycle. | — |
Countries
Canada, Italy, Netherlands, Spain, United States
Contacts
Public ContactKarolina Kasztalska-Kazmierczak
Cromsource
Outcome results
None listed