View clinical trials related to Solid Tumors.
Filter by:Methods Patients received OM-174 twice weekly for a total of 5, 10 or 15 injections of either 600, 800 or 1000 µg/m². Pharmacokinetic analysis and cytokine dosages were performed. Natural Killer cells activity and toll-like receptors 4 polymorphism analysis were also performed.
This is a Phase 1, open-label, dose-escalation trial of avelumab [antibody targeting programmed death ligand 1 (anti PD-L1)] with consecutive parallel group expansion in participants with selected tumor indications. New recruitment is open for all active cohorts. Active cohorts: Escalation revised dosing regimen cohort. Closed cohorts: Non-small cell lung cancer (NSCLC, first line), NSCLC (post-platinum), metastatic breast cancer (MBC), colorectal cancer (CRC), urothelial carcinoma (secondary), mesothelioma, gastric/GEJ cancer (first line switch maintenance and second line), and ovarian cancer (secondary and platinum refractory + liposomal doxorubicin), renal cell carcinoma (second line) melanoma and head, neck squamous cell carcinoma (HNSCC), castrate-resistant prostate cancer (CRPC), adrenocortical carcinoma (ACC) urothelial carcinoma (efficacy), gastric/gastroesophageal junction (GEJ) cancer (third line), renal cell carcinoma (RCC, first line) and escalation phase .
This is a Phase I study to understand the biodistribution of MM-398 and to determine the feasibility of using Ferumoxytol as a tumor imaging agent.
BACKGROUND: - Wee1 is a tyrosine kinase involved in the phosphorylation and inactivation of cyclin-dependent kinase 1 (CDK1/CDC2)-bound cyclin B, resulting in G2 cell cycle arrest in response to deoxyribonucleic acid (DNA) damage to allow time for DNA repair. Recent preclinical data additionally implicates Wee1 in maintenance of genomic integrity during S phase. - Adavosertib (AZD1775) is a selective inhibitor of Wee1 kinase. Recent preclinical model data additionally show single agent anti-tumor activity in multiple cancer cell lines and tumor xenografts. - Preliminary data show AZD1775 is tolerable at lower doses in combination with chemotherapeutic agents. We propose to demonstrate single-agent activity for AZD1775. PRIMARY OBJECTIVE: - To establish the safety and tolerability of single-agent AZD1775 in patients with refractory solid tumors - To determine the pharmacokinetics of AZD1775 in patients with refractory solid tumors SECONDARY OBJECTIVES: - To determine the effect of AZD1775 on markers of DNA damage and apoptosis in tumor tissue and circulating tumor cells - To evaluate the antitumor activity of AZD1775 in patients with refractory solid tumors EXPLORATORY OBJECTIVES: -To identify tumor genomic alterations and gene expression patterns potentially associated with AZD1775 antitumor activity ELIGIBILITY: - Patients must have histologically confirmed solid tumors for which all standard therapy known to prolong survival have failed, or for which standard therapies do not exist. - No major surgery, radiation, or chemotherapy within 3 weeks or (5 half-lives, whichever is shorter) prior to entering the study. - Adequate organ function STUDY DESIGN: - This study will follow a traditional 3+3 design. - In Arm A starting at dose level 1, AZD1775 will be administered orally, twice a day (BID), for 5 doses (Day (D) 1-3) during each cycle. Starting at dose level 2 and onwards, AZD1775 will be administered orally, BID, for 5 doses for the first 2 weeks of each cycle (D1-3 and 8- 10). Each cycle is 21 days (+/- 1 day for scheduling). - Once maximum tolerated dose (MTD) is established, 6 additional patients will be enrolled at the MTD to further evaluate that dose for pharmacokinetics (PK) and pharmacodynamics (PD) endpoints. - A further expansion arm of 6 additional patients with documented tumors harboring breast cancer type 1 or 2 (BRCA)-1 or -2 mutations will also be enrolled at the MTD to further explore the safety of the agent and obtain preliminary evidence of activity in this patient population. - Based on preliminary evidence of drug activity in an alternative once-daily dosing schedule, patients without a documented BRCA mutation will be accrued to a once-daily dosing schedule Arm B, with mandatory paired tumor biopsies at the maximum tolerated single daily dose, to further evaluate PD endpoints. AZD1775 will be administered orally once daily for 5 days (D1-5 and 8-12) during weeks 1 and 2 of each 21-day cycle (+/- 1 day for scheduling). - During the escalation phase, tumor biopsies will be optional and will be evaluated for pharmacodynamic (PD) studies for evidence of Wee1 inhibition DNA damage and repair, and apoptosis (gamma H2A histone family member X (yH2AX), phosphorylated Nbs1 (pNbs1), Rad51, Rabbit polyclonal phospho-cyclin-dependent kinases (pTyr15-Cdk) and caspase 3). During the expansion phase, once MTD is reached, mandatory paired tumor biopsies will be pursued in up to 20 additional patients enrolled at the MTD to further evaluate PD endpoints.
ST1968 is a novel camptothecin derivative which interacts with topoisomerase I-DNA complex, inducing S-Phase specific cytotoxicity. It is endowed with a potent antitumor activity and an increased Therapeutic Index with respect to the clinically used analogues (i.e.irinotecan and topotecan) in some xenograft models (ovary, colon, head & neck, cervix). Anti-tumor activity has been also noted in platinum resistant ovarian cell xenografts and in topoisomerase I mutant prostate cell lines. The acceptable toxicity profile in animals and the activity in camptothecin-resistant cell lines make ST1968 a good candidate for clinical trials.
This is a prospective, randomized, open-label, Phase I, crossover study to assess the effect of food on the bioavailability of AXL1717 including patients with advanced malignant tumors
The primary objective of this study is to determine the safe and tolerable dose level of OPB-111077 for patients with advanced cancer.
Background: Site-specific delivery of anti-cancer therapeutics is paramount for both reducing nonspecific toxicities and increasing efficacy of chemotherapeutic agents. Due to their small molecular size and nonspecific mechanisms of action, most conventional chemotherapies result in significant toxicities that limit the effectiveness of treatment and reduce the overall quality of life for cancer patients. Encapsulation of these toxic agents inside lipid-based carrier systems (so-called liposomes) results in passive targeting of the compounds to solid tumors. The preferential delivery of liposomal drugs to solid tumors is mostly due to altered barrier-properties of tumor-associated vessels. This results in both an improved delivery and at the same time a significantly milder toxicity profile. Recently, the specificity of delivery was further increased by attaching monoclonal antibodies or antibody fragments to the surface of liposomes (=immunoliposomes, antibody-linked nanoparticles). Antibody-coated immunoliposomes attach more selectively to antigens expressed on the target cells and they are internalized more efficiently. Furthermore, there is evidence that drug resistance, a major challenge in cancer treatment, may be overcome by such delivery systems. A logical and accessible target, such as EGFR, is overexpressed on a variety of primary human cancer cells and it is involved in signaling pathways that contribute both to tumor initiation and tumor progression. Recently, the investigators have tested immunoliposomes against the epidermal growth factor receptor (EGFR) in a preclinical setting. Based on the preclinical results we have initiated this phase I clinical trial. Study hypothesis: The investigators hypothesize that anti-EGFR-immunoliposomes selectively deliver cytotoxic compounds to EGFR-overexpressing tumors cells. Specific delivery is supposed to increase efficacy while reducing side-effects of the compound. The primary objective of this phase 1 trial is the determination of the maximum tolerated dose (MTD) for future phase 2 trials of this nanoparticle.
The purpose of this study is to determine the effects of tivantinib on the QTc interval in patients with solid tumors
This is an open-label, multicenter, ascending, multiple dose study of nesvacumab (REGN910/ SAR307746) in combination with aflibercept ("ziv-aflibercept" in the U.S.)