Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Skin and Connective Tissue Diseases

Digestive System Diseases

Gland and Hormone Related Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Carcinoma

Prostatic Neoplasms

Adenocarcinoma

Breast Neoplasms

Colorectal Neoplasms

Pancreatic Neoplasms

Melanoma

Carcinoma, Renal Cell

Liver Neoplasms

Mesothelioma

Mesothelioma, Malignant

Neoplasms, Squamous Cell

Neoplasms by Histologic Type

Skin Diseases

Adenoma

Neoplasms, Glandular and Epithelial

Neoplasms, Mesothelial

Breast Diseases

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Endocrine Gland Neoplasms

Pancreatic Diseases

Endocrine System Diseases

Liver Diseases

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Genital Neoplasms, Male

Genital Diseases

Genital Diseases, Male

Prostatic Diseases

Pancreatic Cancer

Malignant Mesothelioma

All Drugs and Chemicals

Mitogens

PF-06952229 at 375 mg BID in combination with enzalutamide

PF-06952229 at 500 mg BID in combination with enzalutamide

PF-06952229 at 625 mg BID in combination with enzalutamide

PF-06952229 at 750 mg BID in combination with enzalutamide

PF-06952229 at recommended Phase 2 Dose BID

PF-06952229 at recommended phase 2 dose BID in combination with enzalutamide

Oral 7 days on / 7 days off - 28 day cycles (Part 1)

PF-06952229

Prostate Cancer (Part 2). 160mg, capsules, orally, daily

Enzalutamide

Pfizer CT.gov Call Center

A Phase 1 dose escalation and expansion study evaluating safety, tolerability and pharmacokinetics of PF-06952229 in adult patients with advanced solid tumors.

This is a Phase 1, open label, multi center, multiple dose, dose escalation and expansion, safety, tolerability, PK, and pharmacodynamics study of PF 06952229 in previously treated patients with advanced or metastatic cancers that may have high TGFbeta signatures and EMT expression.

The study includes Parts 1A and 1B, which are dose-escalation for monotherapy and combination therapy with enzalutamide, respectively, and Parts 2A and 2B, which are dose expansion for monotherapy and combination therapy with enzalutamide, respectively.

PF-06952229 Treatment in Adult Patients With Advanced Solid Tumors

A PHASE 1 DOSE ESCALATION AND EXPANSION STUDY EVALUATING SAFETY, TOLERABILITY AND PHARMACOKINETICS OF PF 06952229 IN ADULT PATIENTS WITH ADVANCED SOLID TUMORS

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

First cycle DLTs will be utilized to determine the max tolerated dose and future escalations or deescalations. A DLT is any of the predefined set of unacceptable adverse events observed and at least possibly related to investigational agents.

Treatment-related AE is any untoward medical occurrence attributed to study drug in a participant who received study drug.

Laboratory parameters may include: hematology (hemoglobin, hematocrit, red blood cell, platelet and white blood cell count, neutrophils, eosinophils, monocytes, basophils and lymphocytes), chemistry (blood urea nitrogen, creatinine, sodium, potassium, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, albumin, total protein and serum pregnancy test \[for all female participants\]) and urine (urine pregnancy test \[for all female participants\]). Clinical significance of laboratory parameters was determined at the investigator's discretion.

Prostate-specific antigen decline by more than 50% from baseline

Tumor assessment per prostate cancer working group 2 and RECIST v1.1

Single dose and multiple dose PK will be calculated as data permits including Maximum Observed Plasma Concentration (Cmax).

Single dose and multiple dose PK will be calculated as data permits including Time to Reach Maximum Observed Plasma Concentration (Tmax).

Single dose and multiple dose PK will be calculated as data permits including Area Under the Curve (AUC).

Single dose and multiple dose PK will be calculated as data permits including Apparent Oral Clearance (CL/F). Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

Single dose and multiple dose PK will be calculated as data permits including Apparent Volume of Distribution (Vz/F). Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.

The time it takes for the concentration of the study drug in plasma to be reduced by 50%

Prostate-specific antigen decline by more than 50% from baseline.

Number of Participants With Tumor Reponse per PCWG2 and RECIST v1.1

Proportion of patients with a reduction in tumor burden as defined by RECIST 1.1. and PWG3 response criteria.

Time of initial response until documented tumor progression.

The time from Cycle 1 Day 1 dose administration to disease progression or death from any cause.

Time from Cycle 1 Day 1 until death from any cause.

Time from Cycle 1 Day 1 until objective tumor progression.

Time from Cycle 1 Day 1 to objective tumor response.

As data permit, levels of intra-tumor T cells, such as CD8 IHC, will be assessed.

Pfizer

Symptoms and General Pathology

Wounds and Injuries

Inflammation

Fibrosis

Head and Neck Neoplasms

Radiation Injuries

This arm applies the developed rehabilitation assessment software by using two web cameras placed in the front and the side of the subject. The subject sits between two cameras. The observer asks the subject to move the head in each direction, to open the mouth, and to move the tongue. The software will measure CROM, mouth opening, and tongue movement.

This arm applies video-fluoroscopic swallowing (VFSS) and functional oral intake scale (FOIS) to measure the direct, dynamic view of oral, pharyngeal, and upper esophageal function during swallowing with food and liquid mixed with barium, and the functional intake of dysphagic patients, respectively.

In phase 2, this software will be tested in occupational therapists, and head and neck cancer patients results for reliability and validity.

In phase 3, the experiment in the oropharyngeal dysphagia specialists results in content validity, the comparison between the developed software, and VFSS and FOIS results in criterion-related validity, and the experiment in head and neck cancer patients results in reliability.

Rehabilitation assessment software

In phase 3, this study applies VFSS and FOIS for the head and neck cancer patients for comparison with the developed rehabilitation assessment software for criterion-related validity.

VFSS and FOIS

Panrasee Ritthipravat

The current cervical range of motion (CROM) and tongue movement measurement methods are not reliable between observers, which is not practical in real-world usage. This research is to develop the cervical range of motion measurement, and tongue movement estimation software, to compare between the developed software and the current measurement techniques, and to test in clinical aspects for reliability and validity assessment. The investigators investigate the developed software in healthy people in phase 1. In phases 2 and 3, the investigators compare the software to the standard measurement methods in dysphagic patients who have head and neck cancer for reliability and validity.

Rehabilitation Assessment and Progress Tracking System Based on Video Images for Dysphagic Patients

The data requires to be confidential. It is prohibited to share the participant-level data.

The same investigator will repeat cervical range of motion measurement by using the developed rehabilitation software and the standard cervical range of motion (CROM) measurement method from the goniometer.

The cervical range of motion (CROM) measurement by using the developed rehabilitation software and the standard CROM measurement method from the goniometer will be repeated by different observers.

The correlation of the concurrent cervical range of motion (CROM) measurement outcome at approximately the same time between the developed rehabilitation assessment software and the standard CROM measurement method from the goniometer.

The criterion-related validity of the rehabilitation assessment software will be assessed by the correlation between the cervical range of motion measurement by the developed rehabilitation assessment software and the functional swallowing assessment by videofluoroscopic Swallowing Study (VFSS), and functional oral intake scale (FOIS).

Mahidol University

Neoplasm Metastasis

Recurrence

Urinary Bladder Neoplasms

Carcinoma, Transitional Cell

Urinary Bladder Diseases

Transitional Cell Carcinoma

Camurati-Engelmann Disease

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Investigational study drug, administered intravenously every 2 weeks until disease progression or unacceptable toxicity.

PF-03446962 will be administered in 1hr intravenously at a dose of 10 mg/Kg on day 1, then every 2 weeks until the evidence of disease progression or onset of unacceptable toxicity.

PF03446962

Andrea Necchi, MD

Filippo G De Braud, MD

Alessandro M Gianni, MD

Salvage chemotherapy for advanced urothelial cancer (UC) yields suboptimal response rates of 15-40%, a median progression-free survival of 2-4 months and a median overall survival of 6 months. A rationale for targeting angiogenesis in UC is supported by preclinical evidences and early signals of clinical activity of anti-VEGF TKI as demonstrated by our group with the use of pazopanib.

Despite this activity, progression inevitably occurs and mechanisms determining resistance to conventional anti-angiogenic agents are under investigation.

PF-03446962 (Pfizer Inc) is a novel fully human monoclonal antibody (mAb) against ALK1 with dose-dependent antiangiogenic activity as demonstrated in nonclinical studies in a chimera mouse model bearing human tumor xenograft. The investigators suggest that PF-03446962 may increase current results for patients with advanced urothelial cancer failing upfront chemotherapy due to its mechanisms of action. Due to the lack of reliable and reproducible predictors of response as well as of imaging tools to assess tumor response, the trial will provide incorporation of 18FDG-PET/CT and contrast-enhanced ultrasound to stage and evaluate response of urothelial cancers, together with standard imaging modalities (RECIST criteria). Blood and tissue samples will be collected for translational purposes.

This is an open-label, single arm, non randomised, phase II proof-of-concept study of the monoclonal antibody against TGF-beta receptor ALK1 (PF03446962) for patients with urothelial cancer relapsing/progressing after first line chemotherapy.

The study is planned according to Simon's Optimal two-stage design. The primary endpoint is the proportion of patients who are progression-free at 2-months. A 2-month PFS rate of 50% is not promising, while a 70% rate will be promising. In stage 1, 21 evaluable patients will be accrued. If 12 patients at least will be progression-free at 2 months, enrollment will be extended to the 2nd stage for further 24 patients. If, out of the total of 45 patients, 27 at least will be progression-free at 2 months, treatment will be declared worthy for further investigations.

Maximum overall accrual is 45 patients. Type I and type II error rates will be set both at the 10% level.

PF-03446962 in Relapsed or Refractory Urothelial Cancer

Phase II Study of the Fully Human Monoclonal Antibody Against Transforming Growth Factor-beta (TGFβ) Receptor ALK1 (PF-03446962) in Relapsed or Refractory Urothelial Cancer (UC) Failing First-line Treatment.

Progression-free survival (PFS) is defined as the interval from the first dose of study drug to the date of the first documented disease progression or death for any reason, with censoring at the date of last contact for alive patients. A patient who has not progressed or died by the date of the analysis cut-off or when the patient received any further anticancer therapy would have the PFS censored at the time of last adequate tumor assessment before either cut-off date or the commencement of further anticancer therapy date, respectively.

Incidence of adverse events (AEs), defined as any new untoward medical conditions occurrence or worsening of a pre-existing medical condition that does not necessarily have a causal relationship with the study drugs. AEs will be graded according to the NCI-CTC version 4.03 and the relationship of each AEs to study drugs will be assessed by the investigator.

Assessment of response-rate by RECIST v1.1 criteria. RR (%) = CR + PR

Overall Survival (OS) will be calculated as the interval from the date of the first dose of study drug to the date of death for any cause, with censoring at the date of last contact for patients alive. The Kaplan-Meier method will be used to estimate the OS curve (median and 95% confidence interval).

Tissue will be examined in terms of genotyping by high-resolution array comparative genome hybridization (aCGH) and expression of VEGFR, PDGFR, KIT, EGFR, HER2/neu, PTEN on tissue microarrays (TMAs).

Circulating VEGF, soluble VEGFR-1, 2 and -3, soluble c-Kit, IL-6, 8, 12 and HGF will be evaluated by using multiplex ELISA plates.

Circulating tumor cells will be evaluated as a potential response biomarkers.

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Principal Investigator

Heart and Blood Diseases

Diseases and Abnormalities at or Before Birth

Cardiomyopathies

Necrosis

Arrhythmogenic Right Ventricular Dysplasia

Heart Diseases

Heart Defects, Congenital

Congenital Abnormalities

Cardiovascular Abnormalities

Arrhythmogenic Right Ventricular Cardiomyopathy

Fibrinolytic Agents

Anticoagulants

Heparin

Calcium heparin

Carrier of a definite diagnosis of arrhythmogenic dysplasia of the right ventricle in line with the criteria of the Task Force 2010 (see Appendices), admitted for an electrical mapping of the right ventricle

Without heart disease, admitted for a Kent bundle ablation or endocavity procedure / Wolff-Parkinson-White syndrome or common flutter (in subjects in whom the same irrigated material will be used and for whom echocardiography will have excluded associated heart disease).

Peripheral immunological assessment carried out as part of the research, on venous blood at the puncture point necessary for the electrophysiological examination: 1 heparin tube and 1 EDTA tube

Peripheral immunological assessment on venous blood

Immunological assessment carried out as part of the research, on intracardiac material taken during the electrophysiological examination: 1 EDTA tube

Immunological assessment carried out on intracardiac material

Philippe MAURY, MD

Maxime BENEYTO

Audrey TOMASIK

Philippe MAURY

The understanding of ARVC pathophysiology remains incomplete. Several clues indicate that disease progression is mediated through inflammation. The present study aim to document the feasibility of detecting the potential presence of intracardiac local inflammatory components in patients with ARVC.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable condition characterized by right ventricular (RV) dilatation/dysfunction and malignant ventricular arrhythmias. The understanding of ARVC pathophysiology remains incomplete. Several clues indicate that disease progression is mediated through inflammation. First, presence of subepicardial late gadolinium enhancement sharing the same characteristics as the ones found in myocarditis is common on cardiac magnetic resonance imaging (CMR). Second, clinical pathology findings of inflammatory infiltrates of mononuclear cells are frequent and correlate to the extent and severity of ARVC. Finally, from a biological standpoint, the exploratory study conducted by Campian et al. has shown an exaggerated humoral inflammatory response in peripheral blood whilst anti-desmoglein-2 antibodies (targeting a component of the desmosome) emerge as a sensitive and specific biomarker for ARVC. As specific treatments for ARVC are currently lacking, a better understanding of the humoral pathophysiology of the disease could unlock new therapeutic targets. We recently demonstrated that collecting local cardiomyocytes was feasible through irrigated ablation catheters in patients with ARVC. These steerable catheters may easily map the whole right ventricle and locate endocardial or epicardial scars. Aspiration of local blood or cellular material through the inner lumen of the catheter once pressed on the parietal wall may be an interesting technique for retrieving local inflammation markers.

Local Inflammation in Arrhythmogenic Right Ventricular Cardiomyopathy

Rate of Tumor Necrosis Factor alpha in the blood

Rate of Transforming Growth Factor beta in the blood

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
PF-06952229 Treatment in Adult Patients With Advanced Solid Tumors	NCT03685591	Breast Neoplasm... Prostate Neopla... Neoplasms, Squa... Melanoma Mesothelioma Pancreatic Neop... Colorectal Neop... Carcinoma, Rena... Liver Neoplasms	PF-06952229 Enzalutamide	18 Years -	Pfizer
Rehabilitation Assessment and Progress Tracking System Based on Video Images for Dysphagic Patients	NCT05141539	Healthy Head and Neck C...	Rehabilitation ... VFSS and FOIS	18 Years - 80 Years	Mahidol University
PF-03446962 in Relapsed or Refractory Urothelial Cancer	NCT01620970	Transitional Ce...	PF03446962	18 Years -	Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Local Inflammation in Arrhythmogenic Right Ventricular Cardiomyopathy	NCT05209776	Arrhythmogenic ...	Peripheral immu... Immunological a...	18 Years - 99 Years	University Hospital, Toulouse
PF-03446962 in Relapsed or Refractory Urothelial Cancer	NCT01620970	Transitional Ce...	PF03446962	18 Years -	Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Rehabilitation Assessment and Progress Tracking System Based on Video Images for Dysphagic Patients	NCT05141539	Healthy Head and Neck C...	Rehabilitation ... VFSS and FOIS	18 Years - 80 Years	Mahidol University
Rehabilitation Assessment and Progress Tracking System Based on Video Images for Dysphagic Patients	NCT05141539	Healthy Head and Neck C...	Rehabilitation ... VFSS and FOIS	18 Years - 80 Years	Mahidol University

Spots Global Cancer Trial Database for transforming growth factor beta