Completed

A Phase 1 Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of JNJ-42756493, a Pan-Fibroblast Growth Factor Receptor (FGFR) Tyrosine Kinase Inhibitor, in Subjects With Advanced or Refractory Solid Tumors or Lymphoma

What is being tested

JNJ-42756493: Part 1

+ JNJ-42756493: Part 2

+ JNJ-42756493: Part 3

Drug

Who is being recruted

Congenital Abnormalities+28

+ Bone Diseases

+ Bone Diseases, Developmental

Over 18 Years

+12 Eligibility Criteria

See all eligibility criteria

How is the trial designed

Treatment Study

Phase 1

Interventional

Study Start: June 2012

See protocol details

Summary

Principal SponsorJanssen Research & Development, LLC

Last updated: February 3, 2025

Sourced from a government-validated database.Claim as a partner

Study start date: June 15, 2012

Actual date on which the first participant was enrolled.

This is a first-in-human, non-randomized (individuals will not be assigned by chance to study treatments), open-label (individuals will know the identity of study treatments), multicenter (more than 1 hospital work on a study), Phase 1 study. The study consists of 4 parts. Part 1 is the dose-escalation phase, which will be guided by pharmacokinetics, pharmacodynamics and safety. In part 1, safe and biologically active Phase 2 doses (recommended Phase 2 doses [RP2D]) for JNJ-42756493 will be primarily assessed. Participants will be enrolled in sequential cohorts (first cohort will receive the starting dose and subsequent cohorts will receive increased doses of JNJ-42756493). Part 2 is the Dose Confirmation Phase, which consists of a pre and post treatment tumor biopsy cohorts to confirm the RP2D based on the pharmacodynamic effect of JNJ-42756493 on fibroblast growth factor receptor (FGFR) signaling pathway in tumor. Part 3 is the first Dose Expansion Phase, which is designed to evaluate inclusion biomarkers and preliminary clinical activity at the first RP2D. It consists of 4 expansion cohorts, 1 each for squamous cell lung cancer, small cell lung cancer, breast cancer, other solid tumors (Cohorts A, B, C, and D). Part 4 is the second Dose Expansion Phase, which is designed to evaluate inclusion biomarkers and preliminary clinical activity at the second RP2D. Biomarker eligibility has also been refined based on emerging data. It consists of 2 expansion cohorts, Cohort E for non-small cell lung cancer and Cohort F for select solid tumors including breast, urothelial, GBM, ovarian, head & neck, esophageal, gastric, and cholangiocarcinoma (Cohorts E and F). Enrollment of some cohorts may be discontinued due to lack of enrollment or for futility. The study is estimated to take approximately 48 months to complete. Participants' safety will be monitored throughout the study.

NCT01703481

Principal SponsorJanssen Research & Development, LLC

Last updated: February 3, 2025

Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

188 patients to be enrolled

Total number of participants that the clinical trial aims to recruit.

Treatment Study

These studies test new ways to treat a disease, condition, or health issue. The goal is to see if a new drug, therapy, or approach works better or has fewer side effects than existing options.

Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.

Conditions

Criteria

Any sex

Biological sex of participants that are eligible to enroll.

Over 18 Years

Range of ages for which participants are eligible to join.

Healthy volunteers not allowed

If individuals who are healthy and do not have the condition being studied can participate.

Conditions

Pathology

Congenital AbnormalitiesBone DiseasesBone Diseases, DevelopmentalBronchial NeoplasmsCarcinoma, BronchogenicCraniosynostosesDysostosesHemic and Lymphatic DiseasesImmune System DiseasesImmunoproliferative DisordersLung DiseasesLung NeoplasmsLymphatic DiseasesLymphoproliferative DisordersMusculoskeletal AbnormalitiesMusculoskeletal DiseasesCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesNeoplasms by Histologic TypeNeoplasms by SiteRespiratory Tract DiseasesRespiratory Tract NeoplasmsSyndactylySynostosisThoracic NeoplasmsLimb Deformities, CongenitalCraniofacial AbnormalitiesAcrocephalosyndactyliaCarcinoma, Non-Small-Cell LungLymphomaNeoplasmsSmall Cell Lung Carcinoma

Criteria

4 inclusion criteria required to participate

Adequate bone marrow, liver, and renal function within the 14 days prior to Day 1 of Cycle 1 of study drug up until pre-dose of Cycle 1

Eastern Cooperative Oncology Group performance status score 0 or 1

Histologically or cytologically confirmed: solid malignancy or lymphoma that is metastatic or unresectable, and for which standard curative treatment is no longer effective (Part 1); any type of advanced or refractory solid malignancy (excluding lymphoma) that is metastatic or unresectable and for which standard curative treatment is no longer effective (Part 2); advanced or refractory squamous non-small cell lung cancer (Cohort A, Part 3), advanced or refractory small cell lung cancer (Cohort B, Part 3), advanced or refractory breast cancer (Cohort C, Part 3), any type of advanced or refractory solid malignancy (excluding lymphoma) ([consisting of one of the following: gastric, head and neck, lung adenocarcinoma, urothelial, glioblastoma multiforme (GBM), ovarian or prostate]) (Cohort D, Part 3), advanced or refractory non small cell lung cancer(Cohort E, Part 4), any type of advanced or refractory solid malignancy (consisting of one of the following: Breast, Urothelial, GBM, Ovarian, Head & Neck, Esophageal, Gastric, and Cholangiocarcinoma) (Cohort F, Part 4)

Magnesium within 0.85 to 1.25 * institutional normal limits, Sodium greater than or equal to 130 milli equivalent per liter, Potassium within institutional normal limits (within 14 days prior to Day 1 of Cycle 1 up until pre-dose of Cycle 1)

8 exclusion criteria prevent from participating

Any medical condition that requires intact wound healing capacity and is expected to endanger participant safety if wound healing capacity would be severely reduced during administration of the investigational agent

Chemotherapy, targeted therapies, radiotherapy, immunotherapy, or treatment with an investigational anticancer agent within 2 weeks or at least 5 half-lives of the drug, whichever is longer and up to a maximum of 4 weeks (in the case of nitrosoureas and mitomycin C within 6 weeks) before the first administration of study drug. Localized radiation therapy and ongoing luteinizing hormone-releasing hormone (LHRH) agonists, bisphosphonates and denosumab, are permitted

History or current condition of uncontrolled cardiovascular disease

Left ventricular ejection fraction (LVEF) less than 50 percent as assessed by echocardiography (or multi-gated acquisition) performed at screening

Show More Criteria

Study Plan

Find out more about all the medication administered in this study, their detailed description and what they involve.

Treatment Groups

Study Objectives

8 intervention groups are designated in this study

This study does not include a placebo group

Treatment Groups

Group I

Experimental

Dose Escalation, Part 1: Participants will be enrolled in sequential cohorts to determine recommended Phase 2 doses (RP2D).

Group II

Experimental

Dose Confirmation, Part 2: Tumor biopsy cohorts will confirm RP2D.

Group III

Experimental

First dose expansion, Part 3: Participants with squamous non-small cell lung cancer.

Group IV

Experimental

First dose expansion, Part 3: Participants with small cell lung cancer.

Group 5

Experimental

First dose expansion, Part 3: Participants with breast cancer.

Group 6

Experimental

First dose expansion, Part 3: Participants with solid tumors (consisting of one of the following: gastric, head and neck, lung adenocarcinoma, urothelial, glioblastoma multiforme [GBM], ovarian or prostate).

Group 7

Experimental

Second dose expansion, Part 4: Participants with non-small cell lung cancer.

Group 8

Experimental

Second dose expansion, Part 4: Participants with solid tumors (consisting of one of the following: breast, urothelial, GBM).

Study Objectives

Primary Objectives

Secondary Objectives

Study Centers

These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.

This study has 37 locations

Birmingham, United StatesOpen in Google Maps

Tucson, United States

La Jolla, United States

Los Angeles, United States

Completed37 Study Centers