Locally Advanced or Metastatic Esophageal, Esophagogastric Junction or Gastric Cancer MedDRA version: 12.1 Level: LLT Classification code 10056267 Term: Gastroesophageal cancer
Conditions
Interventions
Product Name: IRVALEC (elisidepsin trifluoroacetate)
Product Code: PM02734
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: elisidepsin trifluoroacetate
CAS N
Sponsors
Pharma Mar, S.A. Sociedad Unipersonal
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age = 18 years. 2. Eastern Cooperative Oncology Group (ECOG) PS of = 1 (see Appendix 1). 3. Life expectancy = 3 months. 4. Patients with histologically/cytologically confirmed diagnosis of locally advanced (unresectable) or metastatic esophageal, esophagogastric junction or gastric cancer. Patients must have received one but not more than two prior lines of systemic therapy and must be progressing after last prior therapy before study entry. 5. Adequate bone marrow, renal, hepatic, and metabolic function (assessed = 7 days before first study drug administration): a) Platelet count = 100 x 109/l, hemoglobin = 8.5 g/dl and absolute neutrophil count (ANC) = 1.0 x 109/l. b) Aspartate aminotransferase (AST) and ALT = 3.0 x upper limit of normal (ULN), independently of the presence of liver metastases. c) Direct bilirubin = ULN and total bilirubin = 1.5 x ULN. d) International Normalized Ratio (INR) = 1.5 (except if ongoing oral anticoagulation therapy). e) Renal function: patients with calculated creatinine clearance (using Cockcroft and Gault’s formula, see Appendix 3) = 30 ml/min. f) Albumin = 2.5 g/dl. 6. Recovery to grade = 1 from any AE derived from any previous anticancer treatment (excluding alopecia and grade 2 non-painful peripheral neuropathy). 7. Women of childbearing potential must have a negative serum pregnancy test before study entry. Both women and men must agree to use a medically acceptable method of contraception throughout the treatment period and for six months after discontinuation of treatment. Acceptable methods of contraception include complete abstinence, intrauterine device (IUD), oral contraceptive, subdermal implant and double barrier (condom with a contraceptive sponge or contraceptive suppository). 8. Voluntarily signed and dated written informed consent, obtained from the patient prior to any specific study procedure. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Concomitant diseases/conditions: a) Clinically relevant non-neoplastic liver disease [i.e., cirrhosis; active chronic hepatitis, hepatitis C virus (HCV)/hepatitis B virus (HBV) infection]. b) History or presence of unstable angina, myocardial infarction, clinically relevant valvular heart disease, treatment-requiring and/or symptomatic arrhythmia or congestive heart failure within the last six months prior to enrollment. c) Active uncontrolled infection. d) Known human immunodeficiency virus infection (HIV1/2). e) Limitation of the patient’s ability to comply with the treatment or follow-up protocol. f) Parenteral nutritional support = 25% of total daily caloric requirements. g) Any other major illness that, in the Investigator’s or the Sponsor’s judgment, will substantially increase the risk associated with the patient’s participation in this study. h) Painful peripheral neuropathy = grade 2. i) Any ongoing cancer-related coagulopathy disorder [other than medically treated deep venous thrombosis (DVT) during at least one month]. 2. Known central nervous system (CNS) metastatic involvement. 3. Malignant or non-malignant ascitis = grade 3. 4. Primary histology other than squamous-cell carcinoma or adenocarcinoma. 5. Prior treatment with elisidepsin or KF. 6. Less than 50 kg of body weight (only for patients included in the dose optimization phase). 7. Men or women of childbearing potential who are not using an effective method of contraception as previously described; women who are pregnant or breast feeding. 8. High transfusional requirements (> 4 packages of red blood cells and/or one platelet transfusion) in the last four weeks prior to study entry. 9. Participation in another clinical trial or concomitant treatment with any investigational product in the 4-week period prior to study entry. 10. Patients with a prior invasive malignancy (except non-melanoma skin cancer) who have had any evidence of disease within the last three years. 11. Major surgery performed or planned within four weeks of the start of study treatment (line placement is not considered major surgery). 12. Patients with serious non-healing wound or ulcer. This includes history of abdominal fistula, gastrointestinal perforation, active uncontrolled bleeding or intraabdominal abscess during the last three months before study entry.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Primary endpoint: Rate of tumor control, defined as confirmed objective response of any duration or PFS-4 [absence of disease progression (clinical and/or radiological)] or death at Week 16 ± 1). Secondary efficacy endpoints - Progression-free survival rate at six months and one year (PFS-6 and 1-yr PFS), defined as the percentage of patients who are alive and with no evidence of disease progression at six months and one year after the date of randomization (or after the date of registration if only one of the two schedules proceeds to the Expansion stage), respectively. - Rate of response (RR), defined as the percentage of evaluable patients having at least PR or CR. Antitumor activity will be evaluated according to the RECIST, version 1.1, whenever applicable [by helical contrast enhanced computed tomography (CT) scan or magnetic resonance imaging (MRI), as appropriate] a minimum of eight weeks after initial therapy in all patients with measurable disease. - Duration of response (DR), defined as the time between the date when the response criteria (PR or CR, the first that is reached) are fulfilled and the first date when disease progression, recurrence or death is objectively documented (taking the smallest measurements documented since the treatment started as reference for progressive disease). - Progression-free survival (PFS), defined as the time from the date of randomization (or after the date of registration if only one of the two schedules proceeds to the Expansion stage) to the date of negative assessment (progression or death) or last tumor evaluation. - Overall survival (OS), defined as the time from the date of randomization (or after the date of registration if only one of the two schedules proceeds to the Expansion stage) to the date of death (or the last day when the patient is known to be alive), and rate of survival at one year (1-yr OS), defined as the percentage of patients who are alive at one year after the date of rand | — |
Countries
France, United Kingdom
Outcome results
None listed