|Protocol||Trial Name and Objective|
Phase I/II Randomized Trial of LBH589 (Pabinostat) at Two Dose Levels Combined with Bicalutamide (Casodex) in Men with Castration-Resistant Prostate Cancer
The purpose of this study is to determine the safety (Phase 1) and efficacy, or effectiveness (Phase 2) of an investigational drug, LBH589, in combination with Casodex® for the treatment of prostate cancer. The purpose of the Phase 1 study is to determine the maximum tolerated dose of investigational drug LBH589 in combination with Casodex®. The purpose of the Phase 2 study is to determine the effectiveness of investigational drug LBH589 in combination with Casodex® at the maximum tolerated dose, compared to a lower dose of LBH589 in combination with Casodex®.
Autophagy inhibition to augment mTOR inhibition: A phase I/II trial of RAD001 and hydroxychloroquine in patients with previously treated renal cell carcinoma
Primary Objective Phase I
To determine the maximum tolerated dose of HCQ when administered with daily RAD001 in patients with advanced RCC.
Primary Objective Phase II
To estimate the rate of 6 month PFS in RCC patients receiving RAD001 and HCQ who have had between 1 and 3 prior treatment regimens for advanced disease.
1) To estimate the response rate of this combination.
2) To measure evidence of autophagy inhibition by EM and LC3, p62 immunoblotting in PBMC and tumor tissue
3) To define significant associations between baseline composite p-p70S6K/pAKt score (14) and PFS or response. To characterize significant associations between baseline genetic mutations and outcome and associations between baseline expression of LC3, p62, ATG5 and Beclin and clinical outcome.
Phase I/II Study of Safety and Efficacy of Muscadine Plus (MPX) in Men with Prostate Cancer: A Randomized, Double-Blind Placebo Controlled
Study of the Effects of Two Doses of MPX Capsules on Rising Prostate-Specific Antigen Levels in Men Following Initial Therapy for Prostate Cancer: Phase II
Phase II Primary Objective: To define the effects of placebo and two different daily doses of Muscadine Plus (MPX) on prostate specific antigen doubling time (PSADT) in men who have rising PSA after initial definitive therapy for localized prostate cancer.
Phase II Secondary Objectives: (1) To estimate other measures of PSA kinetics including a)log PSA slope, b)PSAV, c)proportion of men whose PSADT increases greater than 33%, d)greater than 50% reduction in PSA compared with baseline. (2) To assess the adherence, tolerability and toxicity of MPX in both arms of the study.
NCI/CTEP 7998: A Phase I Study of ABT-888 in Combination with Cyclophosphamide in Solid Tumors or Non-Hodgkins Lymphoma
The main purpose of this study is to determine what is the best dose of ABT-888, a drug that prevents proteins from repairing DNA, in combination with cyclophosphamide, a chemotherapy drug that is commonly used to treat many types of cancer. Another goal of this study is to characterize the toxicities of combining ABT-888 and cyclophosphamide. In addition, the pharmacokinetics, or levels of each drug, will be assessed in the blood to evaluate how cyclophosphamide might alter the amount of ABT-888 that is eliminated from the blood.
NCI/CTEP #8850: A Phase I Trial of Riluzole and Sorafenib in Patients with Advanced Solid Tumors and Melanoma (CDUS)
The overall goal of this project is to determine if pharmacological blockade of the metabotropic glutamate receptor 1 (GRM1) signaling pathway with the agent Riluzole, combined with inhibition of RAF signaling with the agent Sorafenib, will result in clinically evident responses in patients with stage IV melanoma.
Phase I Study of Pazopanib in Combination with Weekly Paclitaxel and Carboplatin to Assess the Safety and Tolerability in Patients with Advanced Solid Tumors
1.1 Primary Objective(s)
1.1.1 Determine the safety and tolerability of pazopanib in combination with weekly paclitaxel and weekly carboplatin on Days 1, 8, and 15 every 28 days in patients with advanced solid tumors.
1.1.2 Determine the maximum tolerated dose (MTD) of pazopanib in combination with weekly paclitaxel and weekly carboplatin on Days 1, 8, and 15 every 28 days in patients with advanced solid tumors.
1.1.3 Determine the effect of pazopanib on the pharmacokinetics of paclitaxel and carboplatin.
1.2 Secondary Objective(s)
1.2.1 Assess the clinical activity of pazopanib in combination with paclitaxel and carboplatin administered weekly in patients with solid tumors and in a cohort of triple-negative breast cancer patients.
1.2.2 Evaluate the change in circulating tumor cells in peripheral blood serially in patients enrolled in the dose expansion.
1.2.3 Evaluate blood-based biomarkers, such as cytokines and angiogenic factors (CAF) as potential markers for biological activity, therapeutic sensitivity, or resistance, in patients enrolled in the dose expansion.
NCI/CTEP #8983: A Phase I Trial of MK-2206 and Hydroxychloroquine in Solid Tumors, Melanoma, Renal and Prostate Cancer to Examine the Role of Autophagy in Tumorigenesis
Primary - to define the maximum tolerated dose (MTD) of MK-2206 and hydroxychloroquine (HCQ) when used in combination.
Secondary - (1) to determine the side effects and activity of MK-2206 and hydroxychloroquine when used in combination. (2) to determine if hydroychloroquine alters the pharmcokinetics of MK-2206 due to a drug-drug interaction. (3) to validate biomarkers for autophagy detection
TED12471: A Phase 1 dose-escalation study of the safety and pharmacokinetics of a tablet formulation of SAR245409 administered daily to patients with solid tumors or lymphoma
To evaluate the safety and tolerability of SAR245409 administered
as a tablet formulation on 2 treatment schedules (once daily [QD]
and twice daily [BID] dosing) in patients with solid tumors or
To evaluate the plasma pharmacokinetics (PK) of oral administration
of SAR245409 given as a tablet formulation on QD and BID
treatment schedules in patients with solid tumors or lymphoma
To obtain preliminary information on the effect of food on the plasma
PK of oral administration of SAR245409 as a tablet formulation in
patients with solid tumors or lymphoma
TED12414: International, multicenter, open-label, treatment-extension study for subjects who completed a Phase 1 or Phase 2 parental study to continue receiving treatment with SAR245408 or SAR245409 as a monotherapy or as a combination regimen.
To determine the long-term safety and tolerability of SAR245408 and SAR245409 as a monotherapy or as part of a combination regimen in subjects who are benefiting from treatment.
CC-122-ST-001: A Phase IA/IB, Multi-center,Open-Label, Dose Finding Study To Assess The Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of the Pleiotrophic Pathway modifier CC-122 administered orally to subjects with advanced solid tumors, NHL and Multiple Myeloma.
1. To determine the safety and tolerability of CC-122 given orally and to define the non-tolerable dose, MDT and the recommended phase 2 dose.
2. To determine the PK and extent of urinary excretion of CC-122.
1. Preliminary assessment of the anti-tumor activity of CC-122.
2. To determine the CNS penetration of CC-122.
3. To evaluate the PD effects of CC-122 on gene expression, cytoskeletal structure and cell surface organization in peripheral blood cell components.
4. To evaluate modulation of circulating cytokines in the plasma.
5. To evaluate modulation of immune effector cells and their subtypes in peripheral blood.
6. To evaluate the modulation of cytokine production in ex vivo LPS and anti-CD3 stimulated peripheral blood.
7. To determine the plasmacogenomic relationship between tumor gene sequence or copy number and response.
8. To explore the relationship between PK and PD effects of CC-122.
9. To explore the effect of CC-122 on biomarkers of angiogenesis in pre-and during treatment tumor biopsies when available.
10. To characterize the principle metabolites of CC-122 in plasma and urine.
11.To determine the PK of CC-122 anantiomers in urine and plasma.
12. To assess relationship between renal function and the PK of CC-122.
ECOG E2511 Phase I and Randomized Phase II Double Blind Clinical Trial of Cisplatin and Etoposide in Combination with Veliparib(ABT-888) or Placebo as Frontline Therapy for Extensive Stage Small Cell Lung Cancer
This is a 2-part study consisting of a lead-in phase I dose escalation trial to establish the safety and
determine the optimal dose of veliparib (ABT-888) that will be safely combined with standard doses
of cisplatin and etoposide (CE). This will be followed by a randomized double blind phase II clinical
study to compare CE plus placebo against CE plus veliparib in patients with previously untreated
2.1 Phase I Primary Endpoints
To determine the recommended phase II dose (RP2D) of veliparib to use in combination with
2.2 Phase II Primary Endpoints
To determine whether the addition of ABT-888 to cisplatin etoposide (CE) results in
improved progression free survival (PFS) over CE with placebo in the frontline therapy of
newly diagnosed extensive stage small cell lung cancer
2.3 Phase II Secondary Endpoints
2.3.1 To determine the overall survival (OS) associated with the combination of CE plus
2.3.2 To assess the overall response rate (ORR) as well as complete response rate
(CRR) associated with the combination of CE plus ABT-888
2.3.3 To determine the toxicity profile of the combination of ABT-888 and CE
chemotherapy in this patient population.
2.3.4 To conduct exploratory correlative analysis of the impact of select biomarkers.
2.3.5 To compare the overall toxicity profile and specifically the incidence and severity of
chemotherapy-induced peripheral neuropathy with the addition of ABT-888 to CE
M13-695: A Phase I Study to Evaluate the Safety, Pharmacokinetics and Oral Bioavailability of Veliparib Extended Release Formulations in Subjects with Solid Tumors
Assess and compare the bioavailability of three test extended release (ER) formulations of veliparib with that of the current imemdiate release formulation of veliparib. Evaluate the potential effect of food on the oral bioavailability of three test extended release (ER) formulations of veliparib. Establish the maximum tolerated dose (MTD) and to establish the recommended Phase 2 dose (RPTD) and schedule for one or more of the ER formulations. Secondary objectives of the study are to assess the safety and tolerability of the ER formulations.
TAC113886: A Phase I Dose Escalation Open-Label, Safety, Pharmacokinetic and Pharmacodynamic Study to Determine the Recommended Phase II Dose of GSK1120212 Dosed in Combination with GSK2141795
Primary: Part 1A: To determine the safety, tolerability and recommended Phase II dose of GSK1120212 and GSK2141795 administered in combination orally, once daily continuously. Part 1B: To determine the safety, tolerability and recommended Phase II dose of GSK1120212 and GSK2141795 administered in combination with an alternate schedule (i.e., at least one agent is dosed intermittently). Part 2A, 2B: To evaluate the clinical activity of GSK1120212 and GSK2141795 administered in combination in subjects with solid tumors that are predicted to be sensitive to the inhibition of MEK and/or AKT, including TNBC and BRAF-wild type melanoma.
Secondary: (1) To characterize the PK of GSK1120212 and GSK2141795 for a once daily continuous dosing schedule (Part 1A) and/or an intermittent dosing schedule (Part 1B). (2) Part 1A, Part 1B to evaluate the clinical activity of GSK1120212 and GSK2141795 in subjects with solid tumors. (3) Parts 1 and 2, to characterize the durability of response with GSK1120212 and GSK2141795 dosed orally in combination. (4) To evaluate the pharmacodynamic (PD) response in tumors after treatment with the combination of GSK1120212 and GSK2141795. (5) To explore relationships between study drug PK, PD and clinical activity.
Translational: To explore the association of clinical and PD endpoints with genetic and protein profiles from blood and/or tumor tissue.
Phase I Dose Finding/Phase II Placebo-Controlled Trial of Eltrombopag During Consolidation Therapy in Adults with Acute Myeloid Leukemia (AML) in Complete Remission
2.1 Phase I Primary Objectives
2.1.1 To determine the safety, tolerability and optimal dose of eltrombopag in acute myeloid leukemia patients in complete remission receiving intensive consolidation chemotherapy.
2.1.2 To describe the kinetics of platelet count recovery in acute myeloid leukemia patients in complete remission receiving intensive consolidation chemotherapy who will be receiving eltrombopag.
2.2 Phase I and Phase II Secondary Objective
2.2.1 To determine the plasma concentrations of eltrombopag in acute myeloid leukemia patients in complete remission receiving intensive consolidation chemotherapy (selected dosing regimen only).
2.3 Phase II Primary Objective
2.3.1 To determine if platelet recovery following consolidation chemotherapy is accelerated with eltrombopag.
2.4 Phase II Secondary Objectives
2.4.1 To determine the impact of eltrombopag on platelet transfusion requirements in the setting of consolidation chemotherapy.
2.4.2 To determine the impact of eltrombopag on red blood cell transfusion requirements.
2.4.3 To determine the impact of eltrombopag on occurrence of bleeding events.
2.4.4 To determine the impact of eltrombopag on time to platelet recovery following consolidation chemotherapy.
2.4.5 To determine the impact of eltrombopag on the depth of platelet nadir following a cycle of consolidation chemotherapy.
2.4.6 To determine the duration of platelet nadir in the setting of eltrombopag exposure.
2.4.7 To determine the safety and tolerability of eltrombopag when given at the optimal dose in the setting of consolidation chemotherapy.
2.5 Exploratory Objective
2.5.1 To determine if eltrombopag has an effect on TPO and/or EPO in this setting.
NCI/CTEP# 8317: Phase II trial of cediranib alone or cediranib and lenalidomide in iodine 131-refractory differentiated thyroid cancer
Phase I Primary Objective: to determine the MTD of cediranib plus lenalidomide. Secondary objectives: (1) determine the response rate of cediranib in combination with lenalinomide in patients with iodine refractory, unresectable DTC who have evidence of disease progression within 12 months of study enrollment. (2) determine the toxicity, duration of response, progression free survival, and overall survival in patients with DTC treated with cediranib plus lenalidomide.
Phase II Primary Objectives: (1) determine the progression-free survival rates of single agent cediranib in patients with iodine refractory, unresectable differentiated thyroid cancer (DTC) who have evidence of disease progression within 12 months of study enrollment. (2) determine the progression-free survival rates of cediranib in combination with lenalinomide in patients with iodine refractory, unresectable DTC who have evidence of disease progression within 12 months of study enrollment. (3) compare the progression-free survival curves of single agent cediranib to combination therapy with cediranib with lenalinomide.
Secondary Objectives: (1) determine the response rates and duration of response, early tumor size changes, the toxicity, and overall survival in patients with DTC treated with cediranib or cediranib plus lenalidomide. (2) determine whether the presence of B-RAF or K-RAS mutations in patients with DTC predict response to cediranib or cediranib plus lenalidomide.
A Phase IB/II Pilot Trial of NAB-Paclitaxel Plus Cisplatin Plus Gemcitabine (NABPLAGEMl) in Patients with Previously Untreated Metastatic Pancreatic Ductal Adenocarcinoma
1.The primary objective of this study is to determine the efficacy of nab-paclitaxel plus cisplatin plus gemcitabine for patients with metastatic PDA.
2.Evaluate the safety of cisplatin plus nab-paclitaxel plus gemcitabine