cropped color_logo_with_background.png

A Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of JNJ-42756493 in Adult Participants With Advanced or Refractory Solid Tumors or Lymphoma

Study Purpose

The purpose of this study is to evaluate the safety, pharmacokinetics (study of what the body does to a drug), and pharmacodynamics (study of what a drug does to the body) of JNJ-42756493, a pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, in adult participants with advanced or refractory solid tumors or lymphoma.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - 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) - Eastern Cooperative Oncology Group performance status score 0 or 1.
  • - 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.
  • - 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)

    Exclusion Criteria:

    - 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.
  • - Participants with GBM can be enrolled 2 weeks after last treatment.
  • - History or current condition of uncontrolled cardiovascular disease.
  • - Participants with persistent phosphate greater than upper limit of normal during screening (within 14 days prior to Day 1 of Cycle 1 up until pre-dose of Cycle 1) and despite medical management of phosphate levels.
  • - Participants taking medications known to have a significant risk of causing QTc prolongation and Torsades de Pointes.
  • - Left ventricular ejection fraction (LVEF) less than 50 percent as assessed by echocardiography (or multi-gated acquisition) performed at screening.
  • - 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.
- Participants not recovered from reversible toxicity of prior anticancer therapy (except toxicities which are not clinically significant such as alopecia, skin discoloration, or Grade 1 neuropathy)

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT01703481
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Janssen Research & Development, LLC
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Janssen Research & Development, LLC Clinical Trial
Principal Investigator Affiliation Janssen Research & Development, LLC
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Industry
Overall Status Completed
Countries France, Spain, United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Tumor or Lymphoma
Additional Details

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.

Arms & Interventions

Arms

Experimental: Part 1

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

Experimental: Part 2

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

Experimental: Part 3, Cohort A

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

Experimental: Part 3, Cohort B

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

Experimental: Part 3, Cohort C

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

Experimental: Part 3, Cohort D

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).

Experimental: Part 4, Cohort E

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

Experimental: Part 4, Cohort F

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

Interventions

Drug: - JNJ-42756493: Part 1

Participants will receive 0.5 mg (starting dose) capsule of JNJ-42756493 orally (by mouth) once daily on Day 1 of Cycle 1. Dose of the study medication will be escalated sequentially till the dose limiting toxicity is achieved to determine the recommended part 2 doses (RP2D).

Drug: - JNJ-42756493: Part 2

Participants will receive JNJ-42756493 at the RP2D or below RP2D (maximum tolerated dose from Part 1) orally once daily on a 21 days cycle to confirm RP2D (in Part 2).

Drug: - JNJ-42756493: Part 3

Participants will receive JNJ-42756493 at first RP2D of 9 mg daily in Part 3 orally once daily on a 21 days cycle.

Drug: - JNJ-42756493: Part 4

Participants will receive JNJ-42756493 second RP2D of 10 mg intermittent dosing in Part 4 (with option to increase to 12 mg intermittent dosing based on phosphate level), orally on an intermittent schedule of daily for 7 days followed by 7 days off with a 28-day cycle.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Birmingham, Alabama

Status

Address

Birmingham, Alabama,

Tucson, Arizona

Status

Address

Tucson, Arizona,

La Jolla, California

Status

Address

La Jolla, California,

Los Angeles, California

Status

Address

Los Angeles, California,

Sacramento, California

Status

Address

Sacramento, California,

Santa Monica, California

Status

Address

Santa Monica, California,

Denver, Colorado

Status

Address

Denver, Colorado,

Tampa, Florida

Status

Address

Tampa, Florida,

Augusta, Georgia

Status

Address

Augusta, Georgia,

Chicago, Illinois

Status

Address

Chicago, Illinois,

Goshen, Indiana

Status

Address

Goshen, Indiana,

Boston, Massachusetts

Status

Address

Boston, Massachusetts,

Detroit, Michigan

Status

Address

Detroit, Michigan,

Saint Louis, Missouri

Status

Address

Saint Louis, Missouri,

New Brunswick, New Jersey

Status

Address

New Brunswick, New Jersey,

Albuquerque, New Mexico

Status

Address

Albuquerque, New Mexico,

Charlotte, North Carolina

Status

Address

Charlotte, North Carolina,

Durham, North Carolina

Status

Address

Durham, North Carolina,

Nashville, Tennessee

Status

Address

Nashville, Tennessee,

Dallas, Texas

Status

Address

Dallas, Texas,

Houston, Texas

Status

Address

Houston, Texas,

Tyler, Texas

Status

Address

Tyler, Texas,

Fairfax, Virginia

Status

Address

Fairfax, Virginia,

International Sites

Bordeaux, France

Status

Address

Bordeaux, ,

Caen Cedex 05, France

Status

Address

Caen Cedex 05, ,

Dijon, France

Status

Address

Dijon, ,

Lyon, France

Status

Address

Lyon, ,

Marseille, France

Status

Address

Marseille, ,

Saint Herblain Cedex, France

Status

Address

Saint Herblain Cedex, ,

Villejuif, France

Status

Address

Villejuif, ,

Badalona, Spain

Status

Address

Badalona, ,

Barcelona, Spain

Status

Address

Barcelona, ,

Madrid, Spain

Status

Address

Madrid, ,

Málaga, Spain

Status

Address

Málaga, ,

Pamplona, Spain

Status

Address

Pamplona, ,

Sevilla, Spain

Status

Address

Sevilla, ,

Valencia, Spain

Status

Address

Valencia, ,