soft tissue sarcomas MedDRA version: 20.0 Level: PT Classification code 10075333 Term: Soft tissue sarcoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: L-Annamycin
Product Code: CP-507
Pharmaceutical Form: Lyophilisate for solution for infusion
INN or Proposed INN: ANNAMYCIN
CAS Number: 92689-49-1
Current Sponsor code: CP-507
Other desc
Sponsors
Narodowy Instytut Onkologii im. Marii Sklodowskiej Curie – Panstwowy Instytut Badawczy (NIO-PIB)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. The subject is =18 years old at the time of signing informed consent. 2. The subject has an ECOG performance status =2 with an estimated life expectancy of greater than three months. 3. The subject has a pathologically confirmed diagnosis of STS (including the following pathological subtypes: liposarcoma, leiomyosarcoma, synovial sarcoma, angiosarcoma, undifferentiated pleomorphic sarcoma, myxofibrosarcoma, malignant peripheral nerve sheath tumour, malignant solitary fibrous tumour, and pleomorphic RMS), and documented metastases that are considered eligible for chemotherapy and not eligible for potentially curative surgical resection. 4. The subject must have measurable disease in the lung, defined as, at a minimum, one lesion that can be accurately measured in at least one dimension of >10 mm. Subjects with with additional sites of disease are eligible. 5. The subject had prior anthracycline therapy (cumulative dose of =500 mg/m2) for their disease and has shown the progression of the disease before study entry – for phase II trial maximum of three previous lines of therapy (adjuvant/neoadjuvant regimen is counted as one line of systemic treatment) 6. At least two weeks must have passed following treatment for their disease with chemotherapy, investigational therapy, targeted agents, biological agents, immune modulators, and any toxicities must have resolved to = grade 1 or previous baseline levels no more than four weeks after completing therapy (except alopecia and polyneuropathy). 7. The subject must have adequate laboratory results, including the following: a. Absolute neutrophil count = 1500/mL and platelets =100,000/mL b. Hemoglobin =8.0 g/dL c. Adequate renal function (The Cockcroft-Gault equation will be used to estimate creatinine clearance. This equation is as follows: Creatinine clearance in milliliters per minute= [140-age] x body weight [kg]/72 x plasma creatinine [mg/dL]; multiplied by 0.85 for women. By using this equation, adequate renal function will be deemed to be a creatinine clearance of greater than 60 mL/minute) d. Bilirubin =1.5 x ULN (unless due to Gilbert’s syndrome) e. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 2.5 × ULN (= 5 x ULN in subjects with liver metastases) 8. The subject is able to understand and sign the informed consent document, can communicate with the Investigator, and can understand and comply with the requirements of the protocol. All subjects (men and women) agree to practise effective contraception during the entire study period and after discontinuing the study drug unless documentation of infertility exists. a. Sexually active, fertile women must use two effective forms of contraception (abstinence, intrauterine device, oral contraceptive, or double barrier device) from the time of informed consent and until at least six months after discontinuing the study drug. b. Sexually active men and their sexual partners must use effective contraceptive methods from the time of informed consent until at least six months after discontinuing the study drug. 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 21 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 9
Exclusion criteria
Exclusion criteria: 1. The subject has any condition that, in the opinion of the Investigator, places the subject at unacceptable risk if they were to participate in the study. 2. Metastases to the central nervous system 3. The subject has left ventricular ejection fraction (LVEF) 480 msec, a history of additional risk factors for torsade des pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome) and use of concomitant medications that significantly prolong the QT/QTc interval. 4. The subject has clinically relevant serious comorbid medical conditions including, but not limited to active infection, known positive status for human immunodeficiency virus and/or active hepatitis B or C, cirrhosis, or psychiatric illness/social situations that would limit compliance with study requirements. 5. The subject is pregnant, lactating, or not using adequate contraception. 6. The subject has a known allergy to study drug or excipients. 7. The subject is required to use moderate or strong inhibitors and inducers of cytochrome P450 (CYP) family enzymes CYP3A and CYP2B and transporters that cannot be held three days before treatment and on the day of treatment. 8. Vaccinated with a live vaccine within 28 days prior to the first dose of the study drug. COVID-19 vaccination with mRNA or replication incompetent viral vector vaccines and annual inactivated influenza vaccines are permitted.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •Phase Ib: To establish the safety and tolerability of weekly dosed L-Annamycin in monotherapy in subjects with STS with metastases. •Phase II: To determine the efficacy of L-Annamycin in subjects with STS with metastases ;Secondary Objective: Phase Ib/II: To determine further safety and tolerability for L-Annamycin, the pharmacokinetics of L-Annamycin and its metabolite (annamycinol) and efficacy.;Primary end point(s): •Phase Ib: to determine the Recommended Phase 2 Dose (RP2D) •Phase II: to evaluate 3-month Progression-Free Survival (PFS). ;Timepoint(s) of evaluation of this end point: 6 month PFS | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase Ib/II: To determine further safety and tolerability for L-Annamycin, the pharmacokinetics of L-Annamycin and its metabolite (annamycinol) and efficacy.;Timepoint(s) of evaluation of this end point: 6 months | — |
Countries
Poland
Contacts
Public ContactAgnieszka Janowska
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy (NIO-PIB)
Outcome results
None listed