Antineoplastic Agents

All Drugs and Chemicals

Immune Checkpoint Inhibitors

Enrolled patients will be administered allogeneic γδ T cells with or without the combinations of traditional therapies, including chemotherapy, targeted therapy, radiotherapy, immune checkpoint inhibitors and others.

Phase 1:Enrolled patents will be administered allogeneic γδ T cells from 2x10\^6/kg, 1 x10\^7/kg to 5x10\^7/kg every 2-4 weeks to determine the recommended dose level.

Phase 2: Enrolled patents will be administered allogeneic γδ T cells at the recommended dose level to confirm the efficacy.

Whether or not in combination with other therapies will be determined by research physicians according to the disease status of enrolled patients.

Allogeneic γδ T cells

Weidong Han, M.D

Weidong Han

Yanshan Li

Kaichao Feng

The study is to determine the safety, feasibility and efficacy of allogeneic γδ T cell therapy in patients with solid tumors.

This is an open-label, single-center, phase 1/2 study to evaluate the safety, feasibility and efficacy of allogeneic γδ T cell therapy. In phase 1 period, a typical 3+3 dose-escalation design will be used to determine the optimal dose level based on the incidence of dose-limiting toxicity (DLT), which will be recommended as the fixed dose level in the following expansion period and phase 2. The initial infusion dose level will start from 2x10\^6/kg to 5x10\^7/kg in every 2-4 weeks. Combinations with chemotherapy, targeted therapy, radiotherapy, immune checkpoint inhibitors and other therapies are allowed in this study depending on the disease status of the enrolled patients.

Allogeneic γδ T Cell Therapy for the Treatment of Solid Tumors

An Open-label, Phase 1/2 Study of Allogeneic γδ T Cell Therapy for the Treatment of Solid Tumors

γδ T cells in peripheral blood after infusion will be analysed by TCR or flow cytometry.

The dose escalation strategy will follow the Food and Drug Administration Guideline for design of early phase clinical trials of cellular therapy products.

Safety of the γδ T cell infusion will be based on the risk of treatment-related severe adverse events as identified in the National Cancer Common Terminology Criteria for Adverse Events (CTCAE) version 5.

Objective clinical response will be assessed by investigators every 2 circles during the treatments and every 2 months after treatment until 2 years after the start of 1st cycle of treatment.

The duration of objective response in patients will be recorded until 2years after the start of 1st cycle of treatment

Observation for overall survival l (OS) will be recorded until 2years after the start of 1st cycle of treatment.

Observation for progression-free survival (PFS) will be recorded until 2years after the start of 1st cycle of treatment

Incidence, nature ,and severity of adverse events will be graded according to the NCI CTCAEv5.0.

Chinese PLA General Hospital

Professor

Anticonvulsants

Amino Acids

Bromides

Proline

To assess the tolerability and safety of increasing multiple doses administration of PDM08: 560 μg, 1.12 mg, 2.24 mg, 3.5 mg and 14 mg, 28 mg and 56 mg administered twice a week for four weeks in patients with advanced solid tumours for which there is no standard therapy or the patient is refractory to it.

To assess the tolerability and safety of increasing multiple doses administration of PDM08: 560 μg, 1.12, 2.24, 3.5, 14, 28 and 56 mg administered twice a week for four weeks in patients with advanced solid tumours for which there is no standard therapy or they are refractory to it.

PDM08

Jorge Barriuso, MD, PhD

This phase I study in adult patients with advanced solid tumours is designed to evaluate toxicity, drug exposure (pharmacokinetics) and drug action (pharmacodynamics) of a new molecule, PDM08, administered twice a week cycles of 4 weeks. This drug has shown antitumoral activity in several murine cancer models.

Phase I study, open, dose escalation, in adult patients with advanced solid tumours, to evaluate tolerability, pharmacokinetics and pharmacodynamics of ascending PDM08 doses administered twice a week cycles of 4 weeks.

After checking the safety of the first drug doses, a new dose escalation was proposed and approved by the Ethic Committee and the Medicines Agency.

This clinical trial is carried out in adult patients with advanced solid tumours whose disease has progressed despite standard therapy, or for which there is no standard antineoplastic therapy, or are refractory to it.

In pharmacodynamic non clinical studies, PDM08 presented antitumour activity against different tumour models including, renal, colon, lung, prostate and breast cancer models.

PDM08 Clinical Trial in Advanced Solid Tumors

Phase I Study, Open, Dose Escalation, in Adult Patients With Advanced Solid Tumours, to Evaluate Tolerability, Pharmacokinetics and Pharmacodynamics of PDM08 Administered Twice a Week Cycles of 4 Weeks.

Drug safety will be measured by the number and grade of adverse events, by participant, related to the drug in study (PDM08) in the cohorts studied: 560 μg, 1.12 mg, 2.24 mg, 3.5 mg and 14 mg, 28 mg and 56 mg administered twice a week for four weeks.

The drug will be administered twice a week for four weeks.

Safety and tolerability will be measured considering the adverse events occurred, by participant, related with the drug in study, PDM08, at each cohort.

Drug tolerability will be assessed by determining the DLT. It will be determined for each cohort (increasing multiple doses of PDM08): 560 μg, 1.12 mg, 2.24 mg, 3.5 mg and 14 mg, 28 mg and 56 mg administered twice a week for four weeks). Dose Limiting Toxicity will be considered the dose that produces adverse events of a severity grade 3 or greater, related to the drug in study (PDM08) in the classification specified in the list of Toxicity Criteria of the National Cancer Institute (CTCAE v04.03).

Blood sampling collected on Day 1 and 25 of each cohort cycle.Cohorts (doses): 560 μg, 1.12 mg, 2.24 mg, 3.5 mg and 14 mg, 28 mg and 56 mg administered twice a week for four weeks.

Blood collection scheme: - Dose of 560 μg and 1.12 mg: 0,0.25, 1, 2, 4, 8, 12 hours post-dose, on day 1 and day 25 of each cycle. - Doses of 2.24 mg, 3.5 mg, 14 mg, 28 mg, and 56 mg: 0,0.25, 1, 2, 4, 8, 12, 16 and 24 hours post-dose, on day 1 and day 25 of each cycle.

Pharmacokinetic parameters will be expressed as mean ± standard deviation and confidence interval 95%. Linearity will be analyzed.

Blood sampling will be collected on Day 1 and Day 25 of each cohort cycle.Cohorts(doses): 560 μg, 1.12 mg, 2.24 mg, 3.5 mg and 14 mg, 28 mg and 56 mg administered twice a week for four weeks.

Blood collection scheme:

* Dose of 560 μg and 1.12 mg: 0,0.25, 1, 2, 4, 8, 12 hours post-dose, on day 1 and day 25 of each cycle.
* Dose of 3.5 mg and 14 mg, 28 mg and 56 mg: 0,0.25, 1, 2, 4, 8, 12, 16 and 24 hours post-dose, on day 1 and day 25 of each cycle.

Pharmacokinetic parameters will be expressed as mean ± standard deviation and confidence interval 95%. Linearity will be analyzed.

Blood sampling will be collected on Day 1 and Day 25 of each cohort cycle.Cohorts(dose): 560 μg, 1.12 mg, 2.24 mg, 3.5 mg and 14 mg, 28 mg and 56 mg administered twice a week for four weeks.

Blood collection scheme:

* Dose of 1.12 mg and 2.24 mg: 0,0.25, 1, 2, 4, 8, 12 hours post-dose, on day 1 and day 25 of each cycle.
* Dose of 2.24 mg; 3.5 mg and 14 mg, 28 mg and 56 mg: 0,0.25, 1, 2, 4, 8, 12, 16 and 24 hours post-dose, on day 1 and day 25 of each cycle.

Pharmacokinetic parameters will be expressed as mean ± standard deviation and confidence interval 95%. Linearity will be analyzed.

Blood sampling will be collected on Day 1 and Day 25 of each cohort cycle.Cohorts(dose): 560 μg, 1.12 mg, 2.24 mg, 3.5 mg and 14 mg, 28 mg and 56 mg administered twice a week for four weeks.

Blood collection scheme:

* Dose of 560 μg and 1.12 mg: 0,0.25, 1, 2, 4, 8, 12 hours post-dose, on day 1 and day 25 of each cycle.
* Dose of 2.24 mg, 3.5 mg and 14 mg, 28 mg and 56 mg: 0,0.25, 1, 2, 4, 8, 12, 16 and 24 hours post-dose, on day 1 and day 25 of each cycle.

Pharmacokinetic parameters will be expressed as mean ± standard deviation and confidence interval 95%. Linearity will be analyzed.

Changes in tumour size will be measured by CT (RECIST criteria v.1.1) at each cohort on days 1, 4, 11, 25, 29 and 43 of the study.

Pharmacodynamic parameters will be tabulated as raw values and sorted by dose. Statistical analysis will be performed using ANOVA with repeated measures, including baseline values as cofactor.

Changes in tumour activity will be measured by PET in each cohort on days 1, 4 11, 25, 29 and 43 of the study.

Pharmacodynamic parameters will be tabulated as raw values and sorted by dose. Statistical analysis will be performed using ANOVA with repeated measures, including baseline values as cofactor.

Myeloid cells in peripheral blood (total myeloid cells, monocyte-macrophage series, granulocytes and myeloid suppressor in peripheral blood) will be measured in each cohort on days 1, 4, 11, 25, 29 and 43 of the study.

In order to determine the function of these populations the exresion of membrane markers will be analyze; and membrane markers displayed in relation to the degree of activation of lymphocytes. These parameters will be measured at each cohort on days 1, 4, 11, 25, 29 and 43 of the study.

Serum Immunoglobulins and subtypes (IgG1, IgG2, IgG3, IgG4, IgM, IgA) will be measured at each cohort on days 1, 4, 11, 25, 29 and 43 of the study.

C3 and C4 components of the complement system, CRP, and the total activity of the classical complement pathway. measured as haemolytic capacity CH50,will be measured in serum of all the participants at each cohort on days 1, 4, 11, 25, 29 and 43 of the study.

Serum cytokines that will be measured will be:IL1α, IL1β, IL2, IL4, IL5, IL6, IL7, IL10, IL12, IL17, TNFα, IFNγ, G-CSF, GM-CSF, VEGF. Serum cytokines will be measured in serum at each cohort on days 1, 4, 11, 25, 29 and 43 of the study.

Prodimed S.A.

Topotecan

Olaparib

Poly(ADP-ribose) Polymerase Inhibitors

Topoisomerase I Inhibitors

Enzyme Inhibitors

KU-0059436 (AZD2281)(PARP inhibitor)

James Cassidy

James Carmichael, BSc MBChB MD FRCP

The purpose of this study is to identify a safe and tolerable dose of the drug KU-0059436 that can be given in combination with topotecan chemotherapy in patients with advanced solid tumours

Study to Assess the Safety and Tolerability of a PARP Inhibitor in Combination With Topotecan

A Phase I, Open-Label, Study of the Safety and Tolerability of KU-0059436 and Topotecan in the Treatment of Patients With Advanced Solid Tumours

KuDOS Pharmaceuticals Limited

AstraZeneca

Neoplasms

Symptoms and General Pathology

All Conditions

Neoplasm Metastasis

Bevacizumab

Angiogenesis Inhibitors

Fosbretabulin

Combretastatin

Antineoplastic Agents, Immunological

Growth Inhibitors

Tubulin Modulators

Antimitotic Agents

Combretastatin A4 Phosphate (CA4P)

Bevacizumab (Avastin)

Paul Nathan, MD

Hillori Connors, MS

Peter Harris, MD

The purpose of this study is to determine the safety and tolerability of three dose levels of combretastatin A4 phosphate (CA4P) given intravenously (IV) in combination with bevacizumab every 14 days in patients with advanced solid tumors. The maximum tolerated dose will be defined if it is at one of the three dose levels under study.

Safety Study of Increasing Doses of Combretastatin in Combination With Bevacizumab (Avastin) in Patients With Advanced Solid Tumors

OXC4P1-105: A Phase I Study of the Safety, Tolerability, and Antitumor Activity of Escalating Doses of Combretastatin A4 Phosphate Given in Combination With Bevacizumab to Subjects With Advanced Solid Tumors

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Allogeneic γδ T Cell Therapy for the Treatment of Solid Tumors	NCT04765462	Malignant Solid...	Allogeneic γδ T...	18 Years - 75 Years	Chinese PLA General Hospital
PDM08 Clinical Trial in Advanced Solid Tumors	NCT01380249	Malignant Solid...	PDM08	18 Years -	Prodimed S.A.
Study to Assess the Safety and Tolerability of a PARP Inhibitor in Combination With Topotecan	NCT00516438	Malignant Solid...	KU-0059436 (AZD... Topotecan	18 Years -	AstraZeneca
Study to Assess the Safety and Tolerability of a PARP Inhibitor in Combination With Topotecan	NCT00516438	Malignant Solid...	KU-0059436 (AZD... Topotecan	18 Years -	AstraZeneca
Allogeneic γδ T Cell Therapy for the Treatment of Solid Tumors	NCT04765462	Malignant Solid...	Allogeneic γδ T...	18 Years - 75 Years	Chinese PLA General Hospital
Safety Study of Increasing Doses of Combretastatin in Combination With Bevacizumab (Avastin) in Patients With Advanced Solid Tumors	NCT00395434	Tumors	Combretastatin ... Bevacizumab (Av...	18 Years -	Mateon Therapeutics

Spots Global Cancer Trial Database for malignant solid tumours