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Tumor or LymphomaPhase 1NCT01703481

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

A Phase 1 study testing JNJ-42756493: Part 1, JNJ-42756493: Part 2 and JNJ-42756493: Part 3 in people with Tumor or Lymphoma, run by Janssen Research & Development, LLC at 37 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Tumor or Lymphoma
What is being tested?
JNJ-42756493: Part 1, JNJ-42756493: Part 2 and JNJ-42756493: Part 3
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
188 participants
Where
37 sitesin 3 countries
Study dates
15 Jun 2012to 5 Jul 2017
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)

Who cannot join

  • 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 locations and contacts

37 sites in 3 countries.

37 sites in 3 countries

United States23 sites

  • Study site

    Albuquerque, New Mexico

  • Study site

    Augusta, Georgia

  • Study site

    Birmingham, Alabama

  • Study site

    Boston, Massachusetts

  • Study site

    Charlotte, North Carolina

  • Study site

    Chicago, Illinois

  • Study site

    Dallas, Texas

  • Study site

    Denver, Colorado

  • Study site

    Detroit, Michigan

  • Study site

    Durham, North Carolina

  • Study site

    Fairfax, Virginia

  • Study site

    Goshen, Indiana

  • Study site

    Houston, Texas

  • Study site

    La Jolla, California

  • Study site

    Los Angeles, California

  • Study site

    Nashville, Tennessee

  • Study site

    New Brunswick, New Jersey

  • Study site

    Sacramento, California

  • Study site

    Santa Monica, California

  • Study site

    St Louis, Missouri

  • Study site

    Tampa, Florida

  • Study site

    Tucson, Arizona

  • Study site

    Tyler, Texas

Other trials in United States

France7 sites

  • Study site

    Bordeaux

  • Study site

    Caen

  • Study site

    Dijon

  • Study site

    Lyon

  • Study site

    Marseille

  • Study site

    Saint-Herblain

  • Study site

    Villejuif

Other trials in France

Spain7 sites

  • Study site

    Badalona

  • Study site

    Barcelona

  • Study site

    Madrid

  • Study site

    Málaga

  • Study site

    Pamplona

  • Study site

    Seville

  • Study site

    Valencia

Other trials in Spain

About this study

Official title: 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

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.

Read the detailed description

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.

Being tested
JNJ-42756493: Part 1, JNJ-42756493: Part 2, JNJ-42756493: Part 3, JNJ-42756493: Part 4
Keywords
Tumor, Fibroblast Growth Factor Receptor (FGFR), Non-Small Cell Lung Cancer (NSCLC), Small Cell Lung Cancer (SCLC), JNJ-42756493
Medical subject headings
Neoplasms, Lymphoma, Acrocephalosyndactylia, Carcinoma, Non-Small-Cell Lung, Small Cell Lung Carcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • JNJ-42756493: Part 1Drug

    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).

  • JNJ-42756493: Part 2Drug

    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).

  • JNJ-42756493: Part 3Drug

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

  • JNJ-42756493: Part 4Drug

    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.

Study groups in NCT01703481
Study groupRoleWhat they receive
Part 1ExperimentalDose Escalation, Part 1: Participants will be enrolled in sequential cohorts to determine recommended Phase 2 doses (RP2D).
Receives: Drug: JNJ-42756493: Part 1
Part 2ExperimentalDose Confirmation, Part 2: Tumor biopsy cohorts will confirm RP2D.
Receives: Drug: JNJ-42756493: Part 2
Part 3, Cohort AExperimentalFirst dose expansion, Part 3: Participants with squamous non-small cell lung cancer.
Receives: Drug: JNJ-42756493: Part 3
Part 3, Cohort BExperimentalFirst dose expansion, Part 3: Participants with small cell lung cancer.
Receives: Drug: JNJ-42756493: Part 3
Part 3, Cohort CExperimentalFirst dose expansion, Part 3: Participants with breast cancer.
Receives: Drug: JNJ-42756493: Part 3
Part 3, Cohort DExperimentalFirst 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).
Receives: Drug: JNJ-42756493: Part 3
Part 4, Cohort EExperimentalSecond dose expansion, Part 4: Participants with non-small cell lung cancer.
Receives: Drug: JNJ-42756493: Part 4
Part 4, Cohort FExperimentalSecond dose expansion, Part 4: Participants with solid tumors (consisting of one of the following: breast, urothelial, GBM).
Receives: Drug: JNJ-42756493: Part 4

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part 1: Maximum Tolerated Dose (MTD) of JNJ-42756493

    The maximum tolerated dose as determined in Part 1 of the study will be used as the recommended dose for Part 2, 3 and Part 4.

    Measured: Up to Part 1 Day 84 (Cycle 4, Day 21)

Secondary outcomes (12)

  1. Maximum Observed Plasma Concentration (Cmax) of JNJ-42756493

    The Cmax is the maximum observed plasma concentration.

    Measured: Up to Part 4 Day 84 (Cycle 4, Day 21)

  2. Minimum Observed Plasma Concentration (Cmin) of JNJ-42756493

    The Cmin is the minimum observed plasma concentration.

    Measured: Up to Part 4 Day 84 (Cycle 4, Day 21)

  3. Time to Reach Maximum Observed Plasma Concentration (Tmax) of JNJ-42756493

    The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.

    Measured: Up to Part 4 Day 84 (Cycle 4, Day 21)

  4. Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau)

    The AUCtau is the measure of the plasma drug concentration from time zero to end of dosing interval (24 hour). It is used to characterize drug absorption.

    Measured: Up to Part 4 Day 84 (Cycle 4, Day 21)

  5. Elimination Half Life of JNJ-42756493

    The elimination half-life (t1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).

    Measured: Up to Part 4 Day 84 (Cycle 4, Day 21)

  6. Apparent Volume of Distribution at Steady-State (Vss) of JNJ-42756493

    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 blood concentration of a drug. Vss is the apparent volume of distribution at steady-state, which is estimated by (D/AUC[0-infinity])*(AUMC[0-infinity])/AUC[0-infinity]) where D is the dose of study drug, AUMC(0-infinity) is the area under the first moment curve extrapolated to infinity and AUC(0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time.

    Measured: Up to Part 4 Day 84 (Cycle 4, Day 21)

  7. Total Clearance of JNJ-42756493

    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Total clearance of drug is calculated as dose divided by AUCtau at steady-state.

    Measured: Up to Part 4 Day 84 (Cycle 4, Day 21)

  8. Accumulation Index (AI) of JNJ-42756493

    Accumulation index is calculated by Cmax on Day 1 of Cycle 2/Cmax on Day 1 of Cycle 1 and/or AUCtau on Day 1 of Cycle 2/AUCtau on Day 1 of Cycle 1, where tau is the length of the dosing interval (24 hour).

    Measured: Up to Part 4Day 84 (Cycle 4, Day 21)

  9. Number of Participants With Objective Tumor Response

    Objective response based on assessment of confirmed Complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST). CR defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to less than 10 millimeter (mm). PR defined as at least 30 percent (%) decrease in sum of the diameters of the target lesions taking as reference the Baseline sum diameters. Confirmed responses are those that persist on repeat imaging study for at least 4 weeks after initial documentation of response.

    Measured: Up to Part 4 Day 84 (Cycle 4, Day 21)

  10. Progression Free Survival (PFS)

    Progression free survival is the time period from start of study medication till the disease progression or death, whichever occurs first.

    Measured: Up to Part 4 Day 84 (Cycle 4, Day 21)

  11. Duration of Objective Response

    Duration of objective response is time interval from the first date that criteria for complete response or partial response are met to the first date of progression of disease.

    Measured: Up to Part 4 Day 84

  12. Number of Participants With an Adverse Event

    An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.

    Measured: Up to Part 4 Day 84 (Cycle 4, Day 21)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Oct 2012 (estimated)
  2. Study start15 Jun 2012
  3. Primary completion5 Jul 2017
  4. Study completion5 Jul 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
188 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01703481
Sponsor's protocol ID
CR100845
Other IDs
42756493EDI1001, 2012-000697-34
Status last verified
Jan 2025
First submitted
22 Mar 2012
Last updated
3 Feb 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated device
No

Publications

  • Tabernero J, Bahleda R, Dienstmann R, Infante JR, Mita A, Italiano A, Calvo E, Moreno V, Adamo B, Gazzah A, Zhong B, Platero SJ, Smit JW, Stuyckens K, Chatterjee-Kishore M, Rodon J, Peddareddigari V, Luo FR, Soria JC. Phase I Dose-Escalation Study of JNJ-42756493, an Oral Pan-Fibroblast Growth Factor Receptor Inhibitor, in Patients With Advanced Solid Tumors. J Clin Oncol. 2015 Oct 20;33(30):3401-8. doi: 10.1200/JCO.2014.60.7341. Epub 2015 Aug 31.

    PubMed 26324363

  • Valade E, Dosne AG, Xie H, Kleiman R, Li LY, Perez-Ruixo JJ, Ouellet D. Assessment of the effect of erdafitinib on cardiac safety: analysis of ECGs and exposure-QTc in patients with advanced or refractory solid tumors. Cancer Chemother Pharmacol. 2019 Sep;84(3):621-633. doi: 10.1007/s00280-019-03896-1. Epub 2019 Jul 6.

    PubMed 31280362

  • Bahleda R, Italiano A, Hierro C, Mita A, Cervantes A, Chan N, Awad M, Calvo E, Moreno V, Govindan R, Spira A, Gonzalez M, Zhong B, Santiago-Walker A, Poggesi I, Parekh T, Xie H, Infante J, Tabernero J. Multicenter Phase I Study of Erdafitinib (JNJ-42756493), Oral Pan-Fibroblast Growth Factor Receptor Inhibitor, in Patients with Advanced or Refractory Solid Tumors. Clin Cancer Res. 2019 Aug 15;25(16):4888-4897. doi: 10.1158/1078-0432.CCR-18-3334. Epub 2019 May 14.

    PubMed 31088831

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing JNJ-42756493: Part 1, JNJ-42756493: Part 2 and JNJ-42756493: Part 3 in people with Tumor or Lymphoma, run by Janssen Research & Development, LLC at 37 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 37 sites in United States, France, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1: Maximum Tolerated Dose (MTD) of JNJ-42756493 (time frame: Up to Part 1 Day 84 (Cycle 4, Day 21)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01703481, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Feb 2025.

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