Phase I/II, Multicenter, Open-label, Clinical and Pharmacokinetic Study of PM14 in Combination with Irinotecan in Pretreated Patients with Selected Advanced Solid Tumors
- Conditions
- Patients with Selected Advanced Solid TumorsTherapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2024-514890-24-00
- Lead Sponsor
- Pharma Mar S.A.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 45
Voluntarily signed and dated written informed consent prior to any specific study procedure., Age = 18 years., Eastern Cooperative Oncology Group (ECOG) performance status (PS) = 1., Histologically or cytologically-confirmed selected advanced solid tumors (see below) for which the standard of care therapies have failed, or are intolerant to standard of care therapies that are known to provide clinical benefit. a)Gastrointestinal: esophageal carcinoma, gastric adenocarcinoma, pancreatic adenocarcinoma, biliary tract carcinoma, hepatocarcinoma and poorly differentiated (grade 3) gastroenteropancreatic neuroendocrine neoplasms (Ki 67 index >20%; mitotic count >20%). b)Lung: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). c)Sarcoma: liposarcoma, leiomyosarcoma, synovial sarcoma and Ewing’s sarcoma. d)Gynecological: epithelial ovarian carcinoma (including primary peritoneal disease and/or fallopian tube carcinomas and/or endometrial adenocarcinomas), endometrial carcinoma and carcinoma of cervix. e)Breast: ductal or lobular carcinoma. f)Genitourinary tract tumors: urothelial bladder carcinoma, clear cell renal carcinoma and prostate adenocarcinoma. g)Other: malignant pleural mesothelioma, extrapulmonary small cell carcinoma, and adrenocortical carcinoma., In the Expansion stage only (tumor-specific cohort[s] at the RD): a)Measurable disease according to RECIST v.1.1. b)Documented disease progression per RECIST v.1.1 during or immediately after last therapy according to any of the aforementioned criteria., Washout periods: a)At least three weeks since the last chemotherapy, radiotherapy (RT) >30 Gy, or monoclonal antibody (MAb)-containing therapy. b)At least two weeks since the last biological/investigational single-agent therapy (excluding MAbs) and/or palliative RT (=10 fractions or =30 Gy total dose). c)In patients with hormone-sensitive breast cancer progressing while on hormone therapy (except for luteinizing hormone-releasing hormone [LHRH] analogues in pre-menopausal women or megestrol acetate), all other hormonal therapies must be stopped at least one week before study treatment start. d)Castrate-resistant prostate cancer (CRPC) patients may continue receiving hormone therapy prior to and during study treatment. Note: washout periods will be referred to the day of first cycle administration (Day 1), not to the day of registration, Adequate bone marrow, renal, hepatic, and metabolic function (assessed = 7 days before registration): a)Platelet count = 100 x 109/L, hemoglobin = 9.0 g/dL and absolute neutrophil count (ANC) = 2.0 x 109/L. b)Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 3.0 x the upper limit of normal (ULN), even in the presence of liver metastases. c)Alkaline phosphatase (AP) = 2.5 x ULN (= 5 x ULN if disease-related/in the case of liver metastases). d)Total bilirubin = 1.5 x ULN or direct bilirubin = ULN. e)Calculated creatinine clearance (CrCL) = 30 mL/minute (using Cockcroft-Gault formula). f)Creatine phosphokinase (CPK) = 2.5 x ULN. g)Serum albumin = 3.0 g/dL.*, Recovery to grade = 1 or to baseline from any adverse event (AE) derived from previous treatment (excluding alopecia and/or cutaneous toxicity and/or peripheral neuropathy and/or fatigue grade = 2).
Concomitant diseases/conditions: a)History or presence of unstable angina, myocardial infarction, congestive heart failure, or clinically significant valvular heart disease within the previous year. b)Symptomatic arrhythmia or any uncontrolled arrhythmia requiring ongoing treatment. c)Myopathy or any clinical situation that causes significant and persistent elevation of CPK (> 2.5 x ULN in two different determinations performed one week apart). d)Ongoing chronic alcohol consumption or cirrhosis with Child-Pugh score B or C. Known Gilbert disease. e)Active uncontrolled infection. f)Known human immunodeficiency virus (HIV) or known hepatitis C virus (HCV) infection or active hepatitis B. For hepatitis B, this includes positive tests for both Hepatitis B surface antigen (HBsAg) and quantitative Hepatitis B polymerase chain reaction (PCR). For hepatitis C, this includes positive tests for both Hepatitis C antibody and quantitative Hepatitis C PCR. g)Any past or present chronic inflammatory colon and/or liver disease, past intestinal obstruction, pseudo or sub-occlusion or paralysis. h)Evident symptomatic pulmonary fibrosis or interstitial pneumonitis, pleural or cardiac effusion rapidly increasing and/or necessitating prompt local treatment within seven days. i)Any other major illness that, in the Investigator’s judgment, will substantially increase the risk associated with the patient’s participation in this study (e.g., COVID-19)., Prior treatment with lurbinectedin (Zepzelca®), trabectedin (Yondelis®) or topoisomerase I inhibitors is excluded, if the last dose was administered within six months prior to the first infusion of PM14 and irinotecan., Use of (strong or moderate) inhibitors or strong inducers of CYP3A4 activity within two weeks prior to the first infusion of PM14 and irinotecan., Active or untreated central nervous system (CNS) involvement. Exception: patients with previously treated CNS metastases are eligible provided they have to show radiographic stability (defined as no CNS progression for at least four weeks from post-radiotherapy brain scan to brain scan performed during study screening), and patients should not have neurologic sign/symptoms secondary to the brain metastases or RT. Any steroid treatment must be completed =14 days before the first dose of study treatment. Note: for all SCLC patients regardless of prior history of brain metastases or patients with other solid tumors and previously treated CNS metastases, adequate CNS imaging (contrast enhanced-computed tomography [CT] or magnetic resonance imaging [MRI], if applicable) will be performed at baseline to document any disease involvement, Limitation of the patient’s ability to comply with the treatment or follow-up protocol., Women who are pregnant or breast feeding and fertile patients (men and women) who are not using an effective method of contraception. Women of childbearing potential (WOCBP) must agree to use an effective contraception method to avoid pregnancy during the course of the trial (and for at least six months after the last infusion). Fertile male patients must agree to refrain from fathering a child or donating sperm during the trial and for four months after the last infusion. Valid methods to determine childbearing potential, adequate contraception and requirements of WOCBP partners are described in APPENDIX 2
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method