A Phase 1/2a Study to Assess the Safety and Efficacy of CKD-516 Tab. in Combination With Irinotecan Inj.
Ontology highlight
ABSTRACT:
DISEASE(S): Colorectal Cancer,Colorectal Neoplasms
PROVIDER: 2238528 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
Similar Datasets
Project description:A Phase I study was conducted to determine the tolerability, activity, and immune responses of JEN-101 in dogs with advanced melanoma. A 3+3 dose escalation design was used to evaluate intratumoral injection of JEN-101 at 1, 3, 10, or 20 μg/kg every three weeks for four cycles. A second course was allowable in the absence of disease progression or toxicity. Peripheral blood, serum, and tumor biopsies were collected at baseline and at pre-specified timepoints for pharmacokinetic and immune analyses, which included serum cytokines, immunohistochemistry, and gene expression assessment. JEN-101 was well tolerated with adverse events being fever, lethargy, and isolated elevated liver enzymes. Five dogs experienced grade 3 events and no grade 4 events were observed. Pharmacokinetic analysis showed a trend towards dose-related Cmax within 8 hours of injection. Responding dogs demonstrated increased systemic interferon-γ and IL-10 AUC levels and local recruitment of CD3+ T cells. Increased pro-inflammatory and antigen processing gene expressions were identified in responding lesions.
2024-10-04 | GSE278391 | GEO
Project description:Innovative pro-regenerative treatment strategies for progressive multiple sclerosis (PMS), combining neuroprotection and immunomodulation, represents an unmet need. Neural precursor cells (NPCs) transplanted in animal models of multiple sclerosis promote neuroprotection and remyelination by releasing molecules sustaining trophic support and neural plasticity. We present the results of STEMS, a single dose escalation phase I clinical trial, evaluating the feasibility, safety, and tolerability of intrathecally transplanted human fetal NPCs (hfNPCs) in 12 PMS patients.
2022-11-18 | PXD034840 | Pride
Project description:Innovative pro-regenerative treatment strategies for progressive multiple sclerosis (PMS), combining neuroprotection and immunomodulation, represents an unmet need. Neural precursor cells (NPCs) transplanted in animal models of multiple sclerosis promote neuroprotection and remyelination by releasing molecules sustaining trophic support and neural plasticity. We present the results of STEMS, a single dose escalation phase I clinical trial, evaluating the feasibility, safety, and tolerability of intrathecally transplanted human fetal NPCs (hfNPCs) in 12 PMS patients.
2022-11-18 | PXD034846 | Pride
Project description:Phase I Safety, Pharmacokinetic and Pharmacogenomic Trial of ES-285, a Novel Marine Cytotoxic Agent Administered as an Infusion over 24 h Every 21 Days in Patients with Solid Tumors Purpose: A dose-escalation, phase I study evaluated the safety, pharmacokinetics, pharmacogenomics and efficacy of ES-285, a novel agent isolated from a marine mollusc, in adult cancer patients. Experimental design: Patients received a 24-hour i.v. infusion of ES-285 once every 3 weeks until disease progression or unacceptable toxicity. The starting dose was 4mg/m2. Dose escalation proceeded according to the worst toxicity observed in the previous cohort. Results: 28 patients were treated with 72 courses of ES-285 across 8 dose levels. No doselimiting toxicities (DLTs) were seen between 4mg/m2 and 128mg/m2. Two out of 4 patients treated at 256mg/m2 had dose-limiting reversible grade 3 transaminitis; one patient at 256mg/m2 also had transient grade 3 central neurotoxicity. One of 3 patients subsequently treated at 200mg/m2 died following drug-related central neurotoxicity. Pharmacokinetic studies indicated dose-proportionality with high volume of distribution (median Vss at 256mg/m2 was 2389L, range 1615-4051L) and long elimination half life (median t1/2 at 256mg/m2 was 29h, range 21-32h). The 3 patients with DLT had the highest drug exposure. Pharmacogenomic studies of paired surrogate tissue samples identified changes in gene expression following treatment that correlated with increasing dose. Pre-treatment 59- and 49-gene sets were identified in blood and skin respectively, that may predict DLT. Disease stabilisation for 6 to 18 weeks was recorded in 9 patients. Conclusion: Using this schedule, 128 mg/m2 was considered safe and feasible. At this dose, pharmacologically relevant concentrations of drug were safely achieved with pharmacogenomic studies indicating changes in the expression of genes of potential biological relevance. Keywords: dose response
2009-04-01 | GSE12062 | GEO
Project description:This is a Phase 1/2, multi-center, open-label basket study designed to evaluate the safety and anti-tumor activity of IDE196 in patients with solid tumors harboring GNAQ or GNA11 (GNAQ/11) mutations or PRKC fusions, including metastatic uveal melanoma (MUM), cutaneous melanoma, colorectal cancer, and other solid tumors.
Phase 1 (dose escalation - monotherapy) will assess safety, tolerability and pharmacokinetics of IDE196 via standard dose escalation scheme and determine the recommended Phase 2 dose. Safety and anti-tumor activity will be assessed in the Phase 2 (dose expansion) part of the study.
Phase 1 Tablet and Food Effect Pharmacokinetic (PK) Substudy will assess the PK profile of IDE196 tablet and evaluate the effects of food on the PK profile of IDE196 tablet
Phase 1 (dose escalation - binimetib combination) will assess safety, tolerability and pharmacokinetics of IDE196 and binimetinib via standard dose escalation scheme and determine the recommended Phase 2 dose. Safety and anti-tumor activity will be assessed in the Phase 2 (dose expansion) part of the study.
Phase 1 (dose escalation - crizotinib combination) will assess safety, tolerability and pharmacokinetics of IDE196 and crizotinib via standard dose escalation scheme and determine the recommended Phase 2 dose. Safety and anti-tumor activity will be assessed in the Phase 2 (dose expansion) part of the study. Evaluation of safety and efficacy across multiple doses may be explored in the dose optimization part of the study.
Crizotinib monotherapy with crossover to combination cohort may be assessed for safety and to show the contribution of each study drug to anti-tumor activity.
| 2305357 | ecrin-mdr-crc
Project description:This is an open-label, Phase 2, multicenter study to evaluate the efficacy, safety, tolerability, and pharmacokinetic profiles of botensilimab as monotherapy and in combination with balstilimab or standard-of-care treatments in participants with refractory metastatic colorectal cancer.
| 2760681 | ecrin-mdr-crc
Project description:This study is divided into two parts; Part 1 of the study is a dose escalation phase to select the recommended dose for Part 2 based on the safety, pharmacokinetic, and pharmacodynamic profiles observed after oral administration of GSK525762 in the following subjects: NMC, small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), colorectal cancer (CRC), neuroblastoma (NB), castration resistant prostate cancer (CRPC), triple negative breast cancer (TNBC), estrogen receptor positive (ER positive) breast cancer, and MYCN driven solid tumor subjects. Part 2 of the study will explore the safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical activity of the recommended dose from Part 1 in cohorts comprised of NMC, small cell lung cancer (SCLC), castration resistant prostate cancer (CRPC), triple negative breast cancer (TNBC), and estrogen receptor positive (ER positive) breast cancer subjects. Approximately 60 subjects will be enrolled in the Part 1 and approximately 150 subjects will be enrolled in Part 2. A sub-study will be opened in Part 1 to approximately 10-12 subjects in the United States to investigate the relative bioavailability of the besylate tablet compared to the amorphous free-base tablet at the maximum tolerated dose (MTD) or recommended phase 2 dosing (RP2D), the effect of high-fat high-calorie meal on the bioavailability of the besylate tablet at the MTD or RP2D and the dose proportionality of 2 doses of GSK525762 administered as besylate tablet.
| 2124522 | ecrin-mdr-crc
Project description:Combining PD-L1 blockade with inhibition of oncogenic mitogen-activated protein kinase (MAPK) signaling may result in long-lasting responses in patients with advanced melanoma. This phase 1, open-label, dose-escalation and -expansion study (NCT02027961) investigated safety, tolerability and preliminary efficacy of durvalumab (anti–PD-L1) combined with dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) for patients with BRAF-mutated melanoma (cohort A, n=26), or durvalumab and trametinib given concomitantly (cohort B, n=20) or sequentially (cohort C, n=22) for patients with BRAF-wild type melanoma. Adverse events and treatment discontinuation rates were more common than previously reported for these agents given as monotherapy. Objective responses were observed in 69.2% (cohort A), 20.0% (cohort B) and 31.8% (cohort C) of patients, with evidence of improved tumor immune infiltration and durable responses in a subset of patients with available biopsy samples. In conclusion, combined MAPK inhibition and anti–PD-L1 therapy may provide treatment options for patients with advanced melanoma.
2020-09-24 | GSE158403 | GEO
Project description:This is an open-label, Phase I, dose-escalation study to determine the maximum tolerated dose (MTD) and/or recommended phase two dose (RPTD), and evaluate the safety, efficacy, and pharmacokinetic (PK) profile of ABBV-621 for participants with previously-treated solid tumors or hematologic malignancies.
Only chemotherapy combination (ABBV-621 + FOLFIRI) enrolling participants with RAS-mutant CRC who have received one prior line of therapy is open for enrollment.
| 2238930 | ecrin-mdr-crc
Project description:This study is to assess the safety, tolerability, and biomarkers of protection in healthy malaria-naive adults, who will receive bites from Anopheles stephensi mosquitoes either infected with Plasmodium falciparum Sporozoites (PfRAS) (true-immunization) or noninfected (mock-immunization).
2022-12-31 | GSE192756 | GEO