Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

All Drugs and Chemicals

Hormones

Prolactin Release-Inhibiting Factors

Subjects will be administered with EMD 525797 at a dose of 1500 milligram (mg) (diluted with 0.9 percent \[%\] sodium chloride) as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons.

EMD 525797

Subjects will be administered with EMD 525797 at a dose of 750 mg (diluted with 0.9% sodium chloride) as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons.

Subjects will be administered with placebo (as 0.9% sodium chloride) as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons.

Placebo

All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists).

Standard of Care (SoC)

Medical Responsible

The primary objective of the trial is to evaluate the clinical anti-tumor activity of EMD 525797 administered as 1-hour intravenous infusion every 3 weeks in terms of progression free survival (PFS) time in subjects with asymptomatic or mildly symptomatic metastatic castrate-resistant prostate cancer (mCRPC).

EMD 525797 in Subjects With Asymptomatic or Mildly Symptomatic Metastatic Castrate-resistant Prostate Cancer

A Randomized, Double-blind, Placebo-controlled, Multicenter Phase II Trial Investigating Two Doses of EMD 525797 in Subjects With Asymptomatic or Mildly Symptomatic Metastatic Castrate-resistant Prostate Cancer (mCRPC)

PFS was defined as time from randomization until the first documented sign of objective radiographic disease progression (ORDP) or death from any cause. Death was considered as an event only if it was reported within 12 weeks after last tumor assessment without progression. ORDP was defined as: Bone lesion progression (2 or more new bone lesions compared to baseline) assessed with bone scintigraphy. Assessment was based on Response Evaluation Criteria in Solid Tumors version 1.0 (RECIST v1.0) modified as per Prostate Cancer Working Group 2 (PCWG-2); Soft-tissue lesion progression assessed with CT scans according to RECIST v1.0 modified as per PCWG-2; Presence of skeletal events defined as cord compression/fracture documented via a scheduled or unscheduled radiographic assessment triggered by increased pain or other signs and/or symptoms, based on the investigator's discretion; Non-radiological events, including emergency bone irradiation and surgery, were not investigated.

Overall Survival was defined as the time from the date of randomization to the date of death from any cause.

Time to tumor progression was defined as the time from the date of randomization to the date of ORDP. ORDP was defined as: Bone lesion progression (2 or more new bone lesions compared to baseline) assessed with bone scintigraphy, which had to be confirmed by bone scintigraphy 6 weeks later if subjects remained asymptomatic or mildly symptomatic. Assessments were to be based on RECIST v1.0 modified according to PCWG-2; Soft-tissue lesion progression assessed with CT scans according to RECIST v1.0 modified as per PCWG-2; Presence of skeletal events defined as cord compression or fracture documented via a scheduled or unscheduled radiographic assessment triggered by increased pain or other signs and/or symptoms, based on the investigator's discretion; Non-radiological events, including emergency bone irradiation and surgery, were not investigated.

Presence of tumor response in soft tissue lesions was defined as the presence of at least 1 confirmed complete response (CR) or confirmed partial response (PR) in soft tissue lesions, documented by computed tomography (CT) scans. Presence of DC in soft tissue lesions was defined as the presence of at least 1 confirmed CR or confirmed PR or stable disease (SD) lasting at least 12 weeks after randomization. Tumor response assessments were based on RECIST v1.0 modified according to the PCWG-2. The response was evaluated for subjects with measurable disease at baseline. According to RECIST v1.0, CR=disappearance of all target and non-target lesions; PR=at least 30% decrease in the sum of the longest diameter of target lesions and non-complete response/non-progressive disease in non-target lesions.

New bone lesions were evaluated by bone scintigraphy for subjects with bone lesions at baseline.

Presence of DC in bone lesions was defined as the appearance of less than 2 new bone lesions, documented by bone scintigraphy.

Bone and soft tissue lesions composite tumor response was defined as the presence of both a confirmed CR or PR, documented by CT scans, and a DC in bone lesions, documented by bone scintigraphy. CR was defined as disappearance of all target and non-target lesions and PR was defined as at least 30% decrease in the sum of the longest diameter of target lesions and non-complete response/non-progressive disease in non-target lesions. Presence of DC in bone lesions was defined as the appearance of less than 2 new bone lesions.

Presence of skeletal related events was defined as cord compression or fracture documented via a scheduled or unscheduled radiographic assessment triggered by increased pain or other signs and/or symptoms at the investigator discretion. Non-radiological events, including emergency bone irradiation and surgery, were not investigated.

PSA response was defined as a decrease greater than 50 percent (%) in PSA value from baseline for 2 consecutive evaluations greater than or equal to (\>=) 3 Weeks apart.

An AE was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. A serious adverse event was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs were defined as those AEs that started between first dose of study drug and up to 50 days after last dose.

The apparent total body clearance of drug following intravenous administration (CL); The apparent total body clearance of drug at steady state following intravenous administration (CLss).

The apparent volume of distribution during the terminal phase following intravenous administration (V). The estimate of the apparent volume of distribution at steady state following intravenous administration (Vss).

EMD Serono

Subjects were administered with placebo 0.9 percent (%) sodium chloride as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.

Placebo + SoC

Subjects were administered with EMD 525797 at a dose of 750 milligram (mg) (diluted with 0.9% sodium chloride) as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.

EMD 525797 750 mg + SoC

Subjects were administered with EMD 525797 at a dose of 1500 mg (diluted with 0.9% sodium chloride) as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.

EMD 525797 1500 mg + SoC

Subjects were administered with placebo 0.9% sodium chloride as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.

Subjects were administered with EMD 525797 at a dose of 750 mg (diluted with 0.9% sodium chloride) as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.

Total

Age, Continuous

Sex: Female, Male

All Subjects (ALL) analysis set included subjects who signed the Informed consent document.

Merck KGaA Communication Center

Intention-to-treat (ITT) analysis set included all the subjects who were randomized in the study.

Progression Free Survival (PFS) Time

ITT analysis set included all the subjects who were randomized in the study.

Overall Survival

Time to Tumor Progression

Tumor response

Disease control

ITT analysis set included all the subjects who were randomized in the study. "N" signifies the total number of subjects evaluable for this outcome measure.

Number of Subjects With Presence of Tumor Response and Disease Control (DC) in Soft Tissue Lesions

ITT analysis set included all the subjects randomized in the study. "N" signifies the total number of subjects evaluable for this outcome measure.

Number of Subjects With New Bone Lesions Compared to Baseline

Week 13

Week 19

Week 25

ITT analysis set included all the subjects randomized in the study.

Number of Subjects With Presence of DC in Bone Lesions

Bone and Soft Tissue Lesions Composite Tumor Response

Number of Subjects With Presence of Skeletal Related Events

Number of Subjects With Presence of Prostate Specific Antigen (PSA) Response

Minimum Percentage Change From Baseline in PSA Serum Concentration

Minimum Percentage Change From Baseline in the Number of Circulating Tumor Cells (CTCs)

Overall Minimum Percentage Change From Previous Time Point in Circulating Tumor Cells (CTC)

TEAEs

Serious TEAEs

TEAEs leading to death

TEAEs Leading to Permanent Discontinuation

The Safety analysis set included all the randomized subjects who received at least 1 dose of planned trial treatment and had at least one safety assessment following the trial treatment.

Number of Subjects With Any Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation

First dose: CL (n=4, 6)

Fifth dose: CLss (n=2, 4)

Pharmacokinetic Analysis Set (PKA) included all the randomized subjects who received at least the first dose of the trial drug and provided sufficient data for a concentration time profile for EMD 525797. "n" signifies the number of subjects evaluable for each category in the evaluated group, respectively.

Pharmacokinetic Parameter: Clearance of Intravenously Administered EMD 525797 After First Dose (CL) and Clearance in Steady State of EMD52597 After Fifth Dose (CLss)

First dose (n=4, 6)

Fifth dose (n=2, 4)

PKA included all the randomized subjects who received at least the first dose of the trial drug and provided sufficient data for a concentration time profile for EMD 525797. "n" signifies the number of subjects evaluable for each category in the evaluated group, respectively.

Pharmacokinetic Parameter: Volume of Distribution of EMD 525797 After the First Dose (V) and in Steady State After the Fifth Dose (Vss) of Intravenous Infusion

Data for this outcome measure was presented graphically as per planned analysis but not statistically summarized.

To Explore the Relationship Between Number and/or Changes of Numbers of Biomarker and the Clinical Outcome

Subjects were administered with placebo 0.9% sodium chloride as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the standard of care (SoC) consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.

Overall Study

Nervous System Diseases

Rare Diseases

Brain Neoplasms

Meningioma

Central Nervous System Neoplasms

Nervous System Neoplasms

Neoplasms, Nerve Tissue

Neoplasms by Histologic Type

Neoplasms, Vascular Tissue

Meningeal Neoplasms

Coagulants

Hemostatics

Thrombin

Fibrin Tissue Adhesive

Standard of Care (SoC) include any active or inactive adjunctive treatment to hemostasis methods currently used based on each surgeons surgical practice except for the use of other fibrin sealants.

A porcine-derived fibrin sealant consisting of thrombin and fibrinogen

Bioseal Fibrin Sealant

Richard Kocharian, MD, PhD

The objective of this study is to observe the clinical utility and performance of Bioseal when used as an adjunct to hemostasis versus Standard of Care (SoC) in elective meningioma surgery.

Phase IV Bioseal Study in Brain Tumor Surgery

A Prospective, Randomized, Controlled Phase IV Study to Compare Bioseal Versus Standard of Care as an Adjunct to Hemostasis in Elective Brain Tumor Surgery

The percentage of participants with hemostasis at the Target Bleeding Site (TBS) at 6 minutes following start of treatment application. Hemostasis is defined as no detectable bleeding at the TBS.

The percentage of participants with hemostasis at the Target Bleeding Site (TBS) at 3 minutes following start of treatment application. Hemostasis was defined as no detectable bleeding at the TBS.

Guangzhou Bioseal Biotechnology Co., Ltd.

Ethicon, Inc.

Standard of Care (SoC) included manual compression, cautery, manual compression and cautery with a non-fibrin sealant topical absorbable hemostat (TAH).

A porcine-derived fibrin sealant consisting of thrombin and fibrinogen.

Standard of Care (SoC) included manual compression, cautery, manual compression and cautery with a non-fibrin sealant topical absorbable hemostat (TAH). Standard of Care (SoC)

A porcine-derived fibrin sealant consisting of thrombin and fibrinogen Bioseal Fibrin Sealant

Age, Categorical

Height

Weight

Underweight

Normal

Overweight

Obese

BMI Group

Current Smoker

Former Smoker

Never Smoked

Smoking Status

Adult subjects between the ages of 18 and 75 years were eligible for recruitment into the study.Subject 16225 was enrolled at age 12 and did not match the study inclusion/exclusion criteria. This was logged as a protocol deviation.

Senior Director of Ethicon Clinical R&D

H0: Delta \</= -0.1 HA: Delta \> -0.1 Delta is difference in proportion of successes between Bioseal and SOC gropus (Bioseal minus SOC). Success is defined as hemostasis at the TBS at 6 minutes following treatment application

Hemostasis at the Target Bleeding Site (TBS) at 6 Minutes Following Treatment Application. Hemostasis is Defined as no Detectable Bleeding at the TBS.

Hemostasis at the TBS at 3 Minutes Following Treatment Application

Neurosurgical Complication

Unplanned Intervention

Central Nervous System

Surgical Wound Complication

Incidence of Neurosurgical Complications, Central Nervous System Events and Surgical Wound Complications.

Incidence of Potential Bleeding-related Adverse Events

SoC include Standard of Care (SoC) included manual compression, cautery, manual compression and cautery with a non-fibrin sealant topical absorbable hemostat (TAH).

Glioblastoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Neuroepithelioma

Antineoplastic Agents

Micronutrients

Vitamins

Temozolomide

Trans-sodium crocetinate

Vitamin A

Retinol palmitate

Antioxidants

Protective Agents

Trace Elements

Retinol

Trans Sodium Crocetinate plus the Standard of Care (SOC): SOC composed of radiation and temozolomide for 6 weeks followed by 4 weeks of rest followed by six (6) 28-day cycles of temozolomide

Standard of Care (SOC): SOC composed of radiation and temozolomide for 6 weeks followed by 4 weeks of rest followed by six (6) 28-day cycles of temozolomide

Trans Sodium Crocetinate (TSC) plus the Standard of Care (SOC): SOC composed of radiation and temozolomide for 6 weeks followed by 4 weeks of rest followed by six (6) 28-day cycles of temozolomide

Trans Sodium Crocetinate plus SOC

Standard of Care (SOC)

Harry N Cook, RPH/MBA

Open-label, randomized, controlled, phase 3 safety and efficacy registration trial.

Subjects will be randomized at baseline to the standard of care for first-line treatment of glioblastoma plus Trans Sodium Crocetinate (TSC) or the standard of care.

The standard of care for GBM will consist of temozolomide plus radiation therapy for 6 weeks followed by 28 days of rest followed by 6 cycles of post-radiation temozolomide treatment.

During the radiation treatment period subjects will receive:

1. Focal radiation delivered as 60 Gray/30 fractions scheduled at 2 Gray/day for 5 days each week (Monday through Friday) for 6 weeks.
2. Temozolomide 75mg/m2 orally once daily (usually administered the night preceding each radiation session) starting the evening before the first radiation session over a period of 42 calendar days with a maximum of 49 days.
3. TSC 0.25 mg/kg IV for 3 days each week (Monday, Wednesday, Friday) administered between 45 to 60 minutes prior to each radiation session.

Pneumocystis carinii pneumonia (PCP) prophylaxis is required during Temozolomide + radiation administration, regardless of lymphocyte count and is to continue until recovery of lymphocyte count to less than or equal to Grade 1.

During the 28-day rest period all subjects will receive no treatment.

During the post-radiation 6-cycle temozolomide treatment period subjects will receive:

All subjects will receive: 28-day oral temozolomide (150 mg/m2 first cycle and 200 mg/m2 all subsequent cycles as tolerated) administered on Day 1-5 (Monday through Friday) of each 28-day cycle.

Controls: Will receive oral temozolomide at night at home per the standard of care.

Subjects randomized to TSC: Will receive TSC 1.5 mg/kg (or the dose recommended by the Data Safety Monitoring Board) 1.5 to 2 hours before their temozolomide dose during the daytime for 3 days during the first week of each 28-day cycle (Days 1, 3, 5: Monday, Wednesday, Friday). The Tuesday, Thursday doses will be given at night at home. Long-acting antiemetics may be administered prior to daytime temozolomide dosing on Days 1, 3, 5.

In accordance with the FDA directive of August 22, 2017 the safety, tolerability and pharmacokinetics of TSC at doses between 0.25 mg/kg and up to 1.5 mg/kg in combination with concomitant temozolomide will be assessed via a dose escalation run-in prior to initiating the randomized trial.

The first eight (8) subjects enrolled in the 100-206 trial will be assigned (not randomized between treatments) at Baseline to undergo radiation plus temozolomide plus TSC treatment (0.25 mg/kg) for 6 weekly cycles followed by 4 weeks of rest in standard fashion. At the Week 10 clinic visit the same eight (8) subjects will be assigned to treatment with 2 subjects each assigned to TSC at doses of 0.25, 0.50, 1.0 and 1.5 mg/kg.

The first eight (8) subjects will be studied in parallel and all for two full 28-day cycles with inclusion of appropriate blood sampling collection for TSC and temozolomide pharmacokinetics.

The Data Safety Monitoring Board will examine the resultant safety data after 2 full cycles (Weeks 11 through 18 of post-radiation temozolomide treatment period; Days 1 to 56).

The eight (8) subjects that are a part of the dose-escalation run-in will continue at their assigned TSC dose (0.25, 0.5, 1.0, 1.5 mg/kg) for the Week 19 TSC dosing period.

The Data Safety Monitoring Board will recommend an acceptable TSC dose, if different than 1.5 mg/kg, for the post-radiation temozolomide treatment period prior to the Week 23 TSC dosing period for the eight (8) subjects that are a part of the dose-escalation run-in.

Thereafter, subjects will enter the 100-206 trial and be randomized at Baseline between TSC plus standard of care or the standard of care.

Safety and Efficacy Study of Trans Sodium Crocetinate (TSC) in Newly Diagnosed Glioblastoma (GBM) Biopsy-Only Subjects

Open-label, Randomized, Controlled, Phase 3 Safety and Efficacy Study of Trans Sodium Crocetinate With Radiation Therapy and Temozolomide in Newly Diagnosed Glioblastoma (GBM) Biopsy-Only Subjects

Overall survival will be calculated from randomization to the time of death from any cause

Diffusion Pharmaceuticals Inc

Trans Sodium Crocetinate plus the Standard of Care (SOC): SOC composed of radiation and temozolomide for 6 weeks followed by 4 weeks of rest followed by six (6) 28-day cycles of temozolomide

Trans Sodium Crocetinate plus SOC: Trans Sodium Crocetinate (TSC) plus the Standard of Care (SOC): SOC composed of radiation and temozolomide for 6 weeks followed by 4 weeks of rest followed by six (6) 28-day cycles of temozolomide

Trans Sodium Crocetinate Plus SOC

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

The 100-206 trial was an open-label, dose-escalation safety run-in for what was originally planned as a larger randomized trial. 19 pts were enrolled to ensure that at least 8 pts completed the FDA-specified 24-mo. exposure period. At its Q3 2019 meeting, the DSMB found no adverse safety signal and recommended the trial continue as planned. However, the Sponsor did not have resources to fully support the randomized phase of the study and enrollment in the randomized phase was suspended.

Vice President of Clinical Operations

Overall Survival (OS)

Blood and Lymph Conditions

Hematologic Neoplasms

Hematologic Diseases

Lenvatinib

Pembrolizumab

Complement C3

Complement C3d

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations or more for First Course participants and up to 17 administrations for Second Course participants.

Participants receive pembrolizumab 400 mg via intravenous (IV) infusion on Day 1 of each 6-week cycle for up to 17 administrations or more for First Course participants and up to 8 administrations for Second Course participants.

Participants receive pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle PLUS standard of care (SOC) treatment (or per parent study if there is no SOC) for up to 35 administrations or more for First Course participants and up to 17 administrations for Second Course participants. Participants receiving a pembrolizumab-based combination treatment will receive the dose regimen of the combination drug(s) which is recommended per SOC or was used in the parent study protocol if there is no SOC recommendation.

Participants receive pembrolizumab 400 mg via IV infusion on Day 1 of each 6-week cycle PLUS SOC treatment (or per parent study if there is no SOC) for up to 17 administrations or more for First Course participants and up to 8 administrations for Second Course participants. Participants receiving a pembrolizumab-based combination treatment will receive the dose regimen of the combination drug(s) which is recommended per SOC or was used in the parent study protocol if there is no SOC recommendation.

Participants receive the dose matched non-pembrolizumab SOC treatment (e.g. chemotherapy) they were receiving as per parent study protocol.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
EMD 525797 in Subjects With Asymptomatic or Mildly Symptomatic Metastatic Castrate-resistant Prostate Cancer	NCT01360840	Prostate Cancer...	EMD 525797 EMD 525797 Placebo Standard of Car...	18 Years -	EMD Serono
Phase IV Bioseal Study in Brain Tumor Surgery	NCT02034799	Hemostasis Meningioma Surg...	Bioseal Fibrin ... Standard of Car...	18 Years - 75 Years	Ethicon, Inc.
EMD 525797 in Subjects With Asymptomatic or Mildly Symptomatic Metastatic Castrate-resistant Prostate Cancer	NCT01360840	Prostate Cancer...	EMD 525797 EMD 525797 Placebo Standard of Car...	18 Years -	EMD Serono
Safety and Efficacy Study of Trans Sodium Crocetinate (TSC) in Newly Diagnosed Glioblastoma (GBM) Biopsy-Only Subjects	NCT03393000	Glioblastoma	Trans Sodium Cr... Standard of Car...	18 Years - 70 Years	Diffusion Pharmaceuticals Inc
Long-term Safety and Efficacy Extension Study for Participants With Advanced Tumors Who Are Currently on Treatment or in Follow-up in a Pembrolizumab (MK-3475) Study (MK-3475-587/KEYNOTE-587)	NCT03486873	Solid Tumors Hematologic Mal...	Pembrolizumab Standard of Car... Lenvatinib	18 Years -	Merck Sharp & Dohme LLC
EMD 525797 in Subjects With Asymptomatic or Mildly Symptomatic Metastatic Castrate-resistant Prostate Cancer	NCT01360840	Prostate Cancer...	EMD 525797 EMD 525797 Placebo Standard of Car...	18 Years -	EMD Serono

Spots Global Cancer Trial Database for standard of care (soc)