Anti-Infective Agents

All Drugs and Chemicals

Antineoplastic Agents

Itraconazole

Olaparib

Hydroxyitraconazole

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Clotrimazole

Miconazole

Antifungal Agents

Cytochrome P-450 Enzyme Inhibitors

Hormones

Hormone Antagonists

Cytochrome P-450 CYP3A Inhibitors

Sequential treatments of olaparib alone followed by olaparib+itraconazole, with a washout period in between.

Blood samples taken pre and post dosing with olaparib+/- itraconazole

Pharmacokinetic sampling

Olaparib tablets: Part A 100mg od, days 1 and 9 only. Part B 10x300mg doses over 5 days (300mg bd).

Olaparib tablet dosing

Itraconazole 200mg od Part A days 5 to 11 only

Anitra Fielding

Ruth Plummer, Prof

This is a 3-part study in patients with advanced solid tumours: Part A will assess the effect of itraconazole on the PK parameters of olaparib and will determine the effect of olaparib on the QT interval following single oral dosing; Part B will determine the effect of olaparib on the QT Interval following multiple oral dosing; Part C will allow patients continued access to olaparib after the PK and QT phases and will provide for additional safety data collection. A total of 48 patients are planned to be enrolled; at least 42 evaluable patients will be required to complete the study. Patients will participate as a single cohort in all parts of the study.

To Assess the Effect of Itraconazole (a CYP3A4 Inhibitor) on the Pharmacokinetics of Olaparib, and the Effect of Olaparib on QT Interval Following Oral Dosing of a Tablet Formulation to Patients With Advanced Solid Tumours

A Non-randomised, Open-label, Sequential, Three-part, Phase I Study to Assess the Effect of Itraconazole (a CYP3A4 Inhibitor) on the Pharmacokinetics of Olaparib Following Oral Dosing of a Tablet Formulation, and to Provide Data on the Effect of Olaparib on QT Interval Following Oral Dosing of a Tablet Formulation to Patients With Advanced Solid Tumours

Rate and extent of absorption of olaparib following single (Part A) and multiple (Part B) oral doses of olaparib tablet formulation by assessment of maximum plasma olaparib concentration (Cmax)

Rate and extent of absorption of olaparib following single (Part A) and multiple (Part B) oral doses of olaparib tablet formulation by assessment of area under the plasma concentration time curve from zero to infinity (AUC)

Rate and extent of absorption of olaparib following single (Part A) and multiple (Part B) oral doses of olaparib tablet formulation by assessment of area under the plasma concentration time curve from zero to the last measurable time point, (AUC0-t)

Rate and extent of absorption of olaparib following following single (Part A) and multiple (Part B) oral doses of olaparib tablet formulation by assessment of time to reach maximum plasma concentration for olaparib (tmax)

Rate and extent of absorption of olaparib following following single (Part A) and multiple (Part B) oral doses of olaparib tablet formulation by assessment of area under the plasma concentration time curve from zero to the last measurable time point (AUC0-τ)

Rate and extent of absorption of olaparib following following single (Part A) and multiple (Part B) oral doses of olaparib tablet formulation by assessment of time olaparib apparent clearance (CL/F)

Rate and extent of absorption of olaparib following following single (Part A) and multiple (Part B) oral doses of olaparib tablet formulation by assessment of olaparib apparent volume of distribution (Vz/F)

Rate and extent of absorption of olaparib following following single (Part A) and multiple (Part B) oral doses of olaparib tablet formulation by assessment of olaparib terminal half-life (t1/2).

Rate and extent of absorption of itraconazole by assessment of maximum plasma itraconazole concentration (Cmax).

Rate and extent of absorption of itraconazole by assessment of area under the plasma concentration time curve from zero to the last measurable time point (AUC0-τ)

Rate and extent of absorption of itraconazole by assessment of time to reach maximum plasma concentration for itraconazole (tmax)

Rate and extent of absorption of itraconazole by assessment of itraconazole apparent clearance (CL/F)

Rate and extent of absorption of hydroxyl -itraconazole by assessment of maximum plasma hydroxyl -itraconazole concentration (Cmax).

Rate and extent of absorption of hydroxy-itraconazole by assessment of hydroxy-itraconazole apparent clearance (CL/F)

Rate and extent of absorption of hydroxyl -itraconazole by assessment time to reach maximum plasma concentration for hydroxyl-itraconazole (tmax)

Rate and extent of absorption of hydroxyl -itraconazole by assessment of area under the plasma concentration time curve from zero to the last measurable time point (AUC0-τ)

Assessment of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle (the QT interval), uncorrected and corrected for heart rate (QTc) following single (Part A) and multiple (Part B) oral doses of olaparib tablet formulation.

Assessment of adverse events (AEs), graded by CTCAE (v4.0): Adverse events (AEs) will be collected from the time of signed informed consent throughout the treatment period in Part A and Part B up to and including the 30-day follow-up period. In Part C, AEs will be collected until 12 months after the last patient entered Part C, and including the 30 day follow-up period for any patients who discontinue

These will occur at screening, on the day before dosing in each treatment period and 30 days after last dose in Parts A and B. In Part C, will be assessed weekly for a 28-day period followed by every 4 weeks up to 12 months after the last patient enters Part C and at treatment discontinuation. All will be assessed 30 days after last dose.

Assessment of vital signs (including BP and pulse). These will occur at screening, on the day before dosing in each treatment period and 30 days after last dose in Parts A and B. In Part C, all except ECG will be assessed weekly for a 28-day period followed by every 4 weeks up to 12 months after the last patient enters Part C and at treatment discontinuation. All will be assessed 30 days after last dose.

Assessment of laboratory parameters (clinical chemistry, hematology, and urinalysis) : These will occur at screening, on the day before dosing in each treatment period and 30 days after last dose in Parts A and B. In Part C, all except ECG will be assessed weekly for a 28-day period followed by every 4 weeks up to 12 months after the last patient enters Part C and at treatment discontinuation. All will be assessed 30 days after last dose.

AstraZeneca

Hematinics

Coagulants

Amino Acids

Antibodies

Hepatitis C Antibodies

Immunoglobulins

Liver Extracts

Thrombin

Bilirubin

N-Methylaspartate

Alanine

Aspartic Acid

Patients with:

(i) negative result for serum hepatitis B surface antigen and hepatitis C antibody (ii) total bilirubin ≤1.5 x institutional upper limit of normal (ULN), albumin and prothrombin time within normal limits and must not have ascites (unless related to disease under study) or encephalopathy (iii) aspartate aminotransferase or serum glutamic oxaloacetic transaminase (AST), alanine aminotransferase or serum glutamic pyruvic transaminase (ALT) ≤2.5 x institutional ULN unless liver metastases are present in which case it must be ≤5 x ULN

As defined by the Child-Pugh Classification System.

Part A - single 300mg oral dose olaparib (administered as 2x150mg tablets) Part B - 300mg oral dose olaparib (administered as 2x150mg tablets) bd

Christian Rolfo

This is a 2-part study in patients with advanced solid tumours. Part A will investigate the PK of olaparib in patients with mild or moderate hepatic impairment compared to patients with normal hepatic function; Part B will allow patients with mild or moderate hepatic impairment or normal hepatic function continued access to olaparib after the PK phase and will provide additional safety data.

Study to Assess the Blood Levels and Safety of Olaparib in Patients With Advanced Solid Tumours and Normal Liver Function or Mild or Moderate Liver Impairment

An Open-label, Non-randomised, Multicentre, Comparative, Phase I Study to Determine the Pharmacokinetics, Safety and Tolerability of Olaparib Following a Single Oral 300 mg Dose to Patients With Advanced Solid Tumours and Normal Hepatic Function or Mild or Moderate Hepatic Impairment

Summary of Geometric Least Squares (GLS) Mean for normal, mild and moderate hepatic impairment

Summary of ratio of Geometric Least Squares (GLS) Means

Summary of Geometric Least Squares (GLS) Mean

Summary of Ratio of Geometric Least Squares (GLS) Means

Summary of Geometric Least Squares (GLS) Mean for ratio of mild hepatic impairment compared to normal

Summary of Geometric Least Squares (GLS) Means

Normal (Part A)

Mild (Part A)

Moderate (Part A)

Normal (Part B)

Mild (Part B)

Moderate (Part B)

Olaparib 300 mg (2x150 mg tablets) single dose administered to patients with normal hepatic function

Normal Hepatic Function

Olaparib 300 mg (2x150 mg tablets) single dose administered to patients with mild hepatic function

Mild Hepatic Impairment

Olaparib 300 mg (2x150 mg tablets) single dose administered to patients with moderate hepatic function

Moderate Hepatic Impairment

Total

Age, Continuous

Sex: Female, Male

Anitra Fielding - Senior Research Physician

Moderate Hepatic Function

PK Analysis Set (Part A) One patient excluded from mild impairment arm due to surgery that may affect olaparib absorption.

Maximum Plasma Concentration (Cmax)

Olaparib 300 mg (2x150 mg tablets) single dose administered to patients with mild/normal hepatic function

GLSMean Ratio of Mild to Normal

Olaparib 300 mg (2x150 mg tablets) single dose administered to patients with moderate/normal hepatic function

GLSMean Ratio of Moderate to Normal

PK Analysis Set (Part A) One patient excluded from mild impairment group due to surgery that may affect olaparib absorption.

Ratio of Maximum Plasma Concentration (Cmax) - Mild vs Normal and Moderate vs Normal

Area Under the Plasma Concentration Time Curve From Zero to Infinity (AUC)

Ratio of Area Under the Plasma Concentration Time Curve From Zero to Infinity (AUC) - Mild vs Normal and Moderate vs Normal

Area Under the Plasma Concentration Time Curve From Zero to the Last Measureable Time Point(AUC 0-t)

Ratio of Area Under the Plasma Concentration Time Curve From Zero to the Last Measureable Time Point(AUC 0-t)

Apparent Clearance Following Oral Administration (CL/F)

GLSMean Ration of Mild to Normal

Ratio of Apparent Clearance Following Oral Administration (CL/F)

Time to Reach Maximum Plasma Concentration (Tmax)

Terminal Half-life (t½)

Apparent Volume of Distribution (Vz/F)

Overall Study

Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Symptoms and General Pathology

Carcinoma

Uterine Cervical Neoplasms

Disease Progression

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Antibodies, Monoclonal

Paclitaxel

Carboplatin

Vinorelbine

Nimotuzumab

Albumin-Bound Paclitaxel

Cisplatin

Antineoplastic Agents, Immunological

Injection of 200 mg of Nimotuzumab (weekly during 18 weeks), in combination with chemotherapy (6 cycles, every 21 days: 70 mg / m2 Cisplatin and Vinorelbine 60 mg / m2 (Per Os) at day 1 and day 8.

The objective of the present study is to assess the overall survival of patients after administration of Nimotuzumab hR3 monoclonal antibodies (combined with a chemotherapy) in the treatment of patients with cervix epithelial tumors as first-line treatment.

After the first line , a 200mg dose of hR3 monoclonal antibodies will be given every 14 days until progress.

A second -line chemotherapy is proposed, this is based on Carboplatin (CBP) at AUC of 6, and Paclitaxel (Txl) 175 mg / m2 / SC as 3 hour infusion, every 3 weeks, concomitant with the administration of hR3, every 14 days, until a toxicity limit or an ECOG status greater than 3 appears.

Injection of the Placebo in the same procedures (weekly during 18 weeks), in combination with chemotherapy (6 cycles, every 21 days: 70 mg / m2 Cisplatin and Vinorelbine 60 mg / m2 (Per Os) at day 1 and day 8.

After the first line , a 200mg dose of hR3 monoclonal antibodies will be given every 14 days until progress.

A second -line chemotherapy is proposed, this is based on Carboplatin (CBP) at AUC of 6, and Paclitaxel (Txl) 175 mg / m2 / SC as 3 hour infusion, every 3 weeks, concomitant with the administration of hR3, every 14 days, until a toxicity limit or an ECOG status greater than 3 appears.

Nimotuzumab ( h-R3)

Placebo

Mohamed MECHETI, MD.

The objective of the present study is to estimate the overall survival of patients with cervical cancer after the administration of monoclonal antibody (mAb) Nimotuzumab (hR3) in combination with chemotherapy of first intention. Patients will be randomized in two parallel treatment groups. The first group will receive a dose of 200 mg of monoclonal antibody anti-hR3 (weekly during 18 weeks), combined with a chemotherapy (6 cycles, every 21 days of Cisplatin 70mg/m2, Vinorelbine 60 mg/m2 (Per Os) at D1 and D8 and then 80mg / m2. The second group will receive a placebo in combination with the same chemotherapy regimen as the first group.

At the end of the first intention chemotherapy treatment, a dose of maintenance of Nimotuzumab will be administered at the dose of 200mg every 14 days until progression. A second chemotherapy in the second intention is proposed, this one is based on Carboplatin ( CBP) in an AUC (area under curve) of 6, and Paclitaxel (Txl) in 175 mg / m2 / BSA (body surface area ) in drip of 3 hours, every 3 weeks, concomitant with the administration of hR3, every 14 days, until a limit of toxicity or an ECOG (Eastern Cooperative Oncology Group) status superior to 3, appears.

The objective of the present study is to assess the overall survival of patients after administration of Nimotuzumab hR3 monoclonal antibodies (combined with a chemotherapy) in the treatment of patients with cervix epithelial tumors as first-line treatment.

The patients included will be divided into two treatment groups. The first group receive a 200 mg dose of hR3 monoclonal antibody (weekly for 18 weeks), and chemotherapy (6 cycles, every 21 days: Cisplatin (CDDP) 70 mg / m2 on day 1, Vinorelbine 60 mg / m2 on day 1 and day 8) and then 80mg / m2. The second group receive a placebo in addition to the listed chemotherapy.

After the first line , a 200mg dose of hR3 monoclonal antibodies will be given every 14 days until progress.

A second -line chemotherapy is proposed, this is based on Carboplatin (CBP) at AUC of 6, and Paclitaxel (Txl) 175 mg / m2 / SC as 3 hour infusion, every 3 weeks, concomitant with the administration of hR3, every 14 days, until a toxicity limit or an ECOG status greater than 3 appears.

The survival overall will be considered as the main variable of the response and survival without progression from the antitumor response, the toxicity assessment and the quality of life will be the secondary variables. In addition, the effects may arise during treatment will be identified, and tumor biopsy markers such as, EGF-R and HPV will be determined and those of p53, Ki67 and Bcl-2 by immunohistochemistry (IHC).

It is expected to achieve a difference in survival between the treatment groups of 6.5 vs 10.5 months (0.278 vs 0.62) in favor of the group with mAb hR3.

Evaluate Efficacy of the Association Nimotuzumab(HR3) /Cisplatin-Vinorelbine on Patients With Cervical Carcinom

Multicenter Randomised Double-blind Study to Compare HR3 or Placebo in Combination With Cisplatin-navelbine for Patients With Cervical Carcinoma, Followed in Case of Progression by a Second Line.

El Kendi Pharmaceuticals Manufacturing Company

Central Nervous System Depressants

Psychotropic Drugs

Gastrointestinal Agents

Docetaxel

Fluvoxamine

Serotonin

Lactitol

Vadimezan

ASA404 + Fluvoxamine (Core Phase), ASA404 + either paclitaxel or docetaxel or paclitaxel plus carboplain chemotherapy combination (Extension Phase)

Vadimezan™

Novartis Pharmaceuticals

This trial is designed to study the drug-drug interaction between ASA404 and fluvoxamine, an inhibitor of its metabolic pathway (CYP1A2). The study will consist of two phases. The purpose of the Core Phase is to study the drug drug interaction between fluvoxamine and ASA404. The purpose of the Extension Phase is to provide continued treatment for those patients that have not progressed during the Core Phase and to collect safety data on ASA404 when given in combination with paclitaxel, docetaxel or the paclitaxel plus carboplatin chemotherapy regimen.

Safety and Pharmacokinetics of ASA404 When Given Together With Fluvoxamine, a Selective Serotonin Receptor Reuptake Inhibitor and CYP1A2 Inhibitor

A Multi-center, Open-label, Drug-drug Interaction Study to Assess the Effects of Fluvoxamine on the Pharmacokinetics of ASA404 in Adult Patients With Solid Tumor Malignancies

Renal Insufficiency

Patients with calculated serum creatinine clearance ≥81 mL/min (using Cockcroft-Gault equation).

Patients with calculated serum creatinine clearance 51-80 mL/min (using Cockcroft-Gault equation).

Patients with calculated serum creatinine clearance 31-50 mL/min (using Cockcroft-Gault equation).

This is a 2-part study in patients with advanced solid tumours. Part A will investigate the PK of olaparib in patients with mild or moderate renal impairment compared to patients with normal renal function; Part B will allow eligible study patients continued access to olaparib after the PK phase and will provide additional safety data.

Study to Assess the Blood Levels and Safety of Olaparib in Patients With Advanced Solid Tumours and Normal or Impaired Kidney Function

An Open-label, Non-randomised, Multicentre, Comparative, Phase I Study of the Pharmacokinetics, Safety and Tolerability of Olaparib Following a Single Oral 300 mg Dose to Patients With Advanced Solid Tumours and Normal Renal Function or Renal Impairment

Degree to which olaparib binds to the proteins within blood plasma

Cmax of unbound olaparib; calculated by multiplying total Cmax value by estimated protein binding

AUC of unbound olaparib; calculated by multiplying total AUC by estimated protein binding

Maximum plasma drug concentration of olaparib

Area under plasma concentration-time curve from zero to infinity of olaparib

Area under plasma concentration-time curve from zero to the last measurable time point of olaparib

Time to reach maximum plasma concentration of olaparib

Apparent volume of distribution of olaparib

Renal clearance of olaparib, calculated as the ratio of amount of drug excreted over 24 hours to AUC0-24

AE data were collected on Days 1-5, and at 30 days following the date of last dose of study medication if the subject discontinued in Part A.

Patients from Part A of the study with calculated serum creatinine clearance ≥81 mL/min (using Cockcroft-Gault equation). Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).

Part A Normal Renal Function

Patients in Part A of the study with stable renal impairment with calculated serum creatinine clearance 51 to 80 mL/min (using Cockcroft-Gault equation), for at least 2 months prior to the start of the study.

Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).

Part A Mild Renal Impairment

Patients in Part A of the study with stable renal impairment with calculated serum creatinine clearance 31 to 50 mL/min (using Cockcroft-Gault equation), for at least 2 months prior to the start of the study.

Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).

Part A Moderate Renal Impairment

Patients in Part B of the study with calculated serum creatinine clearance ≥81 mL/min (using Cockcroft-Gault equation). Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).

Part B Normal Renal Function

Patient in Part B of the study with stable renal impairment with calculated serum creatinine clearance 51 to 80 mL/min (using Cockcroft-Gault equation), for at least 2 months prior to the start of the study.

Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).

Part B Mild Renal Impairment

Patient in Part B of the study with stable renal impairment with calculated serum creatinine clearance 31 to 50 mL/min (using Cockcroft-Gault equation), for at least 2 months prior to the start of the study.

Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).

Part B Moderate Renal Impairment

Patients with calculated serum creatinine clearance ≥81 mL/min (using Cockcroft-Gault equation). Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).

Normal Renal Function

Patients with stable renal impairment with calculated serum creatinine clearance 51 to 80 mL/min (using Cockcroft-Gault equation), for at least 2 months prior to the start of the study.

Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).

Mild Renal Impairment

Patients with stable renal impairment with calculated serum creatinine clearance 31 to 50 mL/min (using Cockcroft-Gault equation), for at least 2 months prior to the start of the study.

Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).

Moderate Renal Impairment

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Data are presented for Part A and Part B.

Dr Anitra Fielding

Null hypothesis: There are no clinically significant differences in the PK of olaparib when administered to patients with moderate or mild renal impairment compared to patients with normal renal function.

PK analysis set: All patients who receive an olaparib dose and have full PK sampling up to 96 hours post-dose.

Any patients with major protocol deviations that affected the evaluability of the PK profile were excluded.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
To Assess the Effect of Itraconazole (a CYP3A4 Inhibitor) on the Pharmacokinetics of Olaparib, and the Effect of Olaparib on QT Interval Following Oral Dosing of a Tablet Formulation to Patients With Advanced Solid Tumours	NCT01900028	Solid Tumours	Pharmacokinetic... Olaparib tablet... Itraconazole	18 Years - 130 Years	AstraZeneca
Study to Assess the Blood Levels and Safety of Olaparib in Patients With Advanced Solid Tumours and Normal Liver Function or Mild or Moderate Liver Impairment	NCT01894243	Solid Tumours	Olaparib tablet...	18 Years - 130 Years	AstraZeneca
Evaluate Efficacy of the Association Nimotuzumab(HR3) /Cisplatin-Vinorelbine on Patients With Cervical Carcinom	NCT03413579	Cervical Cancer	Nimotuzumab ( h... Placebo	18 Years - 75 Years	El Kendi Pharmaceuticals Manufacturing Company
Safety and Pharmacokinetics of ASA404 When Given Together With Fluvoxamine, a Selective Serotonin Receptor Reuptake Inhibitor and CYP1A2 Inhibitor	NCT01299415	Solid Tumors	Vadimezan™	18 Years -	Novartis
Study to Assess the Blood Levels and Safety of Olaparib in Patients With Advanced Solid Tumours and Normal or Impaired Kidney Function	NCT01894256	Solid Tumours	Olaparib tablet...	18 Years - 75 Years	AstraZeneca
Study to Assess the Blood Levels and Safety of Olaparib in Patients With Advanced Solid Tumours and Normal Liver Function or Mild or Moderate Liver Impairment	NCT01894243	Solid Tumours	Olaparib tablet...	18 Years - 130 Years	AstraZeneca

Spots Global Cancer Trial Database for oncology,

Every month we try and update this database with for oncology, cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for oncology,

Every month we try and update this database with for oncology, cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for oncology, cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.