Status and phase
Conditions
Treatments
About
This is an open-label, multi-center, dose-escalation and dose-expansion phase I study to evaluate the safety, tolerability, PK characteristics and anti-tumor activity of PARP inhibitor IMP4297 and temozolomide combination therapy in patients with advanced solid tumors and with ES-SCLC who develops disease progression after 1L platinum-based regimen.
Full description
This study will be conducted in two parts. Part I of the study will be dose escalation evaluation to determine the MTD and/or recommended phase 2 dose(RP2D) of IMP4297 in combination with temozolomide. Part II of the study will be conducted in two expansion cohorts (sensitive ES-SCLC cohort and resistant ES-SCLC cohort) to further evaluate the anti-tumor activity, safety and tolerability of this regimen in ES-SCLC patients.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
The patient must voluntarily participate in this clinical study and be willing and able to provide written informed consent/assent for the trial.
Age ≥ 18 years old on the day of signing informed consent form (ICF), males or females
Patient population:
Patients have adequate organ function, as indicated by the following laboratory values (had not received blood transfusion, apheresis infusion, erythropoietin, granulocyte colony-stimulating factor, and other relevant medical support within 28 days before the administration of the IPs
Female patients should meet at least 1 of the following criteria before they can participate in the study:
Male patients are eligible to participate in the study if they have undergone vasectomy or agree to use effective methods of contraception from study entry up to 6 months after the last dose of the IP(s).
Exclusion criteria
Patients with primary tumor in central nervous system (CNS) and active or untreated central CNS metastases and/or carcinomatous meningitis should be excluded. Patients with previously treated brain metastases may participate provided they are clinically stable for at least 4 weeks and, have no evidence of new or enlarging brain metastases and no requirements for corticosteroids 14 days prior to dosing with IPs.
Patients with serious acute and chronic infections, including:
Patients who have previously received PARP inhibitors.
Patients who have received strong CYP3A4 inhibitors or inducers prior to the first dose of the IPs (the patient can be enrolled if the elution period prior to the first dose of the IPs is ≥5 half-lives), or patients who need to continue receiving these medications during the study period.
Patients who have received a live-virus vaccination within 28 days of the planned start of study.
Patients who have participated a study of an investigational agent and received study therapy or used an investigational device within 28 days of the first dose of treatment.
Patients have not recovered (i.e., to ≤Grade 1 or to baseline, as evaluated by NCI-CTCAE v5.0) from cytotoxic therapy-induced AEs, except for alopecia.
Patients who have received anti-cancer chemotherapy, endocrine therapy, herbal/alternative therapies (including Chinese herbal or Chinese medicine or proprietary Chinese medicine), or other anti-cancer systemic treatment (except anti-cancer antibody) within 5 half-lives or 14 days, whichever is longer prior to the first dose of the IPs. Patients who have received anti-cancer antibody within 28 days prior to the first dose of the IPs.
Patients who have undergone a major surgery within 28 days prior to the study treatment, or have undergone a radical radiotherapy, or have undergone a palliative radiotherapy within 14 days prior to the study treatment, or have used a radioactive drug (Strontium, Samarium, etc.) within 56 days prior to the study treatment.
In Part II of the study, patients who have other malignancies within 2 years prior to the first dose of the IPs will be excluded. except for radically treated locally curable malignant tumors, such as basal or squamous cell skin cancer, superficial bladder cancer, or prostate, cervical or breast carcinoma in situ.
Patients with uncontrolled pleural effusion, pericardial effusion or ascites requiring recurrent drainage procedures (once monthly or more frequently). Please contact medical monitor if any further discussion or clarification is needed.
Patients with a history of seizures.
Patients with a previously documented diagnosis of myelodysplastic syndrome (MDS).
Patients who have major cardiovascular diseases (such as congestive heart failure, unstable angina, atrial fibrillation, arrhythmia); patients who have acute myocardial infarction, unstable angina, stroke, or transient ischemic attack within 6 months prior to the first dose of the IPs; patients who have congestive heart failure (≥New York Heart Association [NYHA] Classification Class II); patients who have severe arrhythmia requiring medication (including QT interval [QTc] prolongation corrected by the Fridericia's formula [QTcF] of more than 480 msec, pacemaker installation, and previous diagnosis of congenital long QT syndrome).
Patients who are unable to swallow capsules. Patients have gastrointestinal illnesses that may affect the absorption of oral medication IMP4297 and temozolomide.
Patients with a known hypersensitivity to IMP4297, temozolomide or any of the excipients of the products.
Patients who have received transplantation including patients with previous allogeneic bone marrow transplant.
Patients known to have a history of alcoholism or drug abuse.
The investigator believes that the patient's underlying disease may put the patient at risk in IP administration or may affect the evaluation of toxicity events or AEs.
Primary purpose
Allocation
Interventional model
Masking
113 participants in 1 patient group
Loading...
Central trial contact
Min Song
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal