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NeoplasmsPhase 1NCT01962532

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

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

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 determine a dose for future development and to evaluate the safety, pharmacokinetics, pharmacodynamics, and efficacy profiles of JNJ-42756493 in Japanese and other Asian patients with advanced or refractory solid tumors or lymphoma. Read more about this study

Who is it for?
Ages 20 years and older
Conditions the study is for
Neoplasms, Lymphoma, Adenocarcinoma
What is being tested?
Part 1: JNJ-42756493 and Part 2: JNJ-42756493
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
19 participants
Where
3 sitesJapan
Study dates
21 Aug 2013to 28 Jan 2016
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 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Part 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 2: Histologically or cytologically confirmed gastric adenocarcinoma including gastroesophageal junctions that is metastatic, locally advanced or unresectable, and for which standard treatment is no longer effective or tolerable
  • Eastern Cooperative Oncology Group performance status score 0 or 1
  • Adequate bone marrow, liver, and renal function according to protocol-defined criteria within the 7 days prior to Day 1 of Cycle 1
  • Laboratory values within protocol -defined parameters
  • Agrees to protocol-defined use of effective contraception
  • Negative urine pregnancy test (urine or serum beta human chorionic gonadotropin [beta-HCG]) at screening for women of child bearing potential

Who cannot join

  • Has had chemotherapy, radiotherapy, immunotherapy, or treatment with an investigational anticancer agent within 3 weeks (nitrosoureas and mitomycin C within 6 weeks) before the first administration of study drug (localized radiation therapy for palliative purposes and ongoing luteinizing hormone-releasing hormone agonists and antagonists for patients with prostate cancer, bisphosphonates and denosumab are permitted
  • History or current condition of uncontrolled cardiovascular disease as defined in the protocol
  • Taking medications known to have a risk of causing QTc prolongation and Torsades de Pointes or known as strong CYP3A inhibitors or inducers
  • Left ventricular ejection fraction less than (<) 50 percent (%) as assessed by echocardiography (or multi-gated acquisition [MUGA]) performed at screening
  • Uncontrolled intercurrent illness including, but not limited to, poorly controlled hypertension or diabetes, ongoing active infection, psychiatric illness, or a risk of gastrointestinal perforation
  • Woman who is pregnant, breast-feeding, or planning to become pregnant or is a man who plans to father a child, while the participant is enrolled in this study and is within 3 or 5 months, respectively, after the last dose of the study drug
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  • Not recovered from reversible, clinically significant toxicity of prior anticancer therapy
  • Presence of 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
  • Major surgery within 4 weeks before enrollment
  • Known human immunodeficiency virus infection
  • Known hepatitis B or C (except hepatocellular carcinoma)
  • Active, symptomatic, or untreated brain metastasis

Trial locations and contacts

3 sites in 1 country.

Japan3 sites
  • Study site

    Kashiwa

  • Study site

    Matsuyama

  • Study site

    Tokyo

Other trials in Japan

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 determine a dose for future development and to evaluate the safety, pharmacokinetics, pharmacodynamics, and efficacy profiles of JNJ-42756493 in Japanese and other Asian patients with advanced or refractory solid tumors or lymphoma.

Read the detailed description

This is an open-label (identity of assigned study drug will be known), multicenter, 2-part, Phase 1 dose escalation/expansion to evaluate the safety, pharmacokinetics (study of what the body does to a drug), pharmacodynamics (study of what a drug does to the body) and clinical activity of JNJ-42756493 administered orally once daily in 21-day cycles or 28 days cycles of intermittent dosing regimen (7 days on/7 days off) to Japanese and Asian participants >=20 years of age with advanced or refractory solid tumors or lymphoma who are not candidates for approved or available therapies. Approximately 40 participants will be enrolled. In Part 1 Participants will be required to be hospitalized after the first dose on Day 1 of Cycle 1 until Day 2 of Cycle 2 (for daily continuous dosing) or until Day 14 of Cycle 1 (for intermittent dosing), however extension of hospitalization will be allowed until Day 2 of Cycle 2 according to investigators clinical judgment. The Part 1 dose-escalation phase is designed to determine the recommended Phase 2 dose (RP2D) based on safety, pharmacokinetic, and pharmacodynamic data of JNJ-42756493. Participants will be enrolled in sequential cohorts based on the 3+3 dose-escalation scheme; the first cohort will receive the starting dose and subsequent cohorts will receive increased doses of JNJ-42756493. After the last participants in each cohort completes Cycle 1, the Safety Evaluation Team (SET) will evaluate the safety and pharmacokinetic data according to protocol-defined criteria and make the decision whether to escalate the dose in a new cohort. To determine the recommended Phase 2 dose, the SET will review all safety, pharmacokinetic, and pharmacodynamic data from Part 1 before initiation of Part 2. The total number of participants enrolled in Part 1 will depend on the dose level at which the recommended Phase 2 dose is established. After the recommended Phase 2 dose is established, the Part 2 dose-expansion phase will be opened. Part 2 study will be done in a molecularly-defined subset of Participants with gastric adenocarcinoma including gastroesophageal junctions at the RP2D. In Part2, Participants can be hospitalized until Day 8 of Cycle 1 as needed. In addition, extension of hospitalization will be allowed until Day 15 of Cycle 1 according to investigator's clinical judgment. In Part 2, approximately 25 participants will be treated at the recommended Phase 2 dose as 28 days cycles of intermittent dosing regimen in order to evaluate fibroblast growth factor receptor target modulation in tumor, to further elaborate safety, pharmacokinetics, and pharmacodynamics of JNJ-42756493, as well as to evaluate preliminary clinical responses. Participants who are tolerating study drug treatment and achieve clinical responses or stable disease will continue to receive study drug at the same dose until disease progression, unacceptable toxicity, or withdrawal of consent. Serial pharmacokinetic and pharmacodynamic samples will be collected, and safety and efficacy will be monitored throughout the study.

Being tested
Part 1: JNJ-42756493, Part 2: JNJ-42756493
Keywords
Neoplasms, Lymphoma, Advanced or refractory solid tumors, Advanced or refractory lymphoma, Gastric adenocarcinoma, Gastroesophageal junctions, JNJ-42756493, Pharmacokinetics, Japanese, Asian, Pharmacodynamics
Medical subject headings
Neoplasms, Lymphoma, Adenocarcinoma

What participants receive

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

  • Part 1: JNJ-42756493Drug

    JNJ-42756493 dose escalation starting at dose of 2 mg orally daily for 21-day cycles and 28 day cycles Intermitting dosing regimen (7 days on and 7 days off) up to the maximum tolerated dose in order to determine the recommended Phase 2 dose.

  • Part 2: JNJ-42756493Drug

    Recommended Phase 2 JNJ-42756493 dose determined in Part 1 administered orally for 28-days cycles (Intermitting dosing regimen).

Study groups in NCT01962532
Study groupRoleWhat they receive
Part 1: Dose Escalation (Daily Dosing)ExperimentalDose escalation of JNJ-42756493 is to occur until a dose at which <33 percent of participants experience a dose-limiting toxicity, the maximum concentration of JNJ-42756493 is less than the protocol-defined cardiovascular threshold, and JNJ-42756493 is biologically active. Participants will receive study drug once day on Day 1 of Cycle 1 followed by a 2-day drug-free period (Days 2 and 3 of Cycle 1) and continues throughout the 21 day cycle. For all subsequent cycles once a day for 21 days.
Receives: Drug: Part 1: JNJ-42756493
Part 1: Dose Escalation (Intermittent Dosing)ExperimentalIntermitting dosing regimen will be 28 days (7 days on and 7 days off). Participants will receive JNJ-42756493 on Days 1 to 7 and Days 15 to 21 of each cycle; JNJ-42756493 will not be administered on Days 8 to 14 and Days 22 to 28 of each cycle.
Receives: Drug: Part 1: JNJ-42756493
Part 2: Dose ExpansionExperimentalParticipants will receive the recommended Phase 2 JNJ-42756493 dose determined in Part 1 as Intermitting dosing regimen (28 days, 7 days on and 7 days off). Participants who are tolerating study drug treatment and achieve clinical responses or stable disease will continue to receive study drug at the same dose until disease progression, unacceptable toxicity, or withdrawal of consent.
Receives: Drug: Part 2: JNJ-42756493

What is being measured

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

  1. Number of participants affected by adverse events by MedDRA system organ class (SOC) and Preferred term (PT)

    Measured: Up to 30 days after the last dose of study medication

Secondary outcomes (12)
  1. Maximum observed plasma concentration of JNJ-42756493

    Measured: Up to Part 2 Cycle 4 (each cycle is 28 days) Day 1

  2. Minimum observed plasma concentration of JNJ-42756493

    Measured: Up to Part 2 Cycle 4 (each cycle is 28 days) Day 1

  3. Time correspondent to the maximum observed plasma concentration of JNJ-42756493

    Measured: Up to Part 2 Cycle 4 (each cycle is 28 days) Day 1

  4. Area under the plasma concentration-time curve from time 0 to 24 hours of JNJ-42756493

    Measured: Up to Part 2 Cycle 4 (each cycle is 28 days) Day 1

  5. Half-life of JNJ-42756493

    Measured: Up to Part 2 Cycle 4 (each cycle is 28 days) Day 1

  6. Apparent volume of distribution of JNJ-42756493

    Measured: Up to Part 2 Cycle 4 (each cycle is 28 days) Day 1

  7. Total clearance of drug of JNJ-42756493

    Measured: Up to Part 2 Cycle 4 (each cycle is 28 days) Day 1

  8. Accumulation index of JNJ-42756493

    Measured: Up to Part 2 Cycle 4 (each cycle is 28 days) Day 1

  9. Number of participants with complete response

    Measured: Up to Part 2 Cycle 4 (each cycle is 28 days) Day 28

  10. Number of participants with partial response

    Measured: Up to Part 2 Cycle 4 (each cycle is 28 days) Day 28

  11. Number of participants with stable disease

    Measured: Up to Part 2 Cycle 4 (each cycle is 28 days) Day 28

  12. Number of participants with progressive disease

    Measured: Up to Part 2 Cycle 4 (each cycle is 28 days) Day 28

Timeline

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

  1. First posted14 Oct 2013 (estimated)
  2. Study start21 Aug 2013
  3. Primary completion28 Jan 2016
  4. Study completion28 Jan 2016

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
19 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01962532
Sponsor's protocol ID
CR102388
Other IDs
42756493GAC1001
Status last verified
May 2019
First submitted
26 Jul 2013
Last updated
15 May 2019
Results posted
No
Data monitoring committee
No

Publications

  • Nishina T, Takahashi S, Iwasawa R, Noguchi H, Aoki M, Doi T. Safety, pharmacokinetic, and pharmacodynamics of erdafitinib, a pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, in patients with advanced or refractory solid tumors. Invest New Drugs. 2018 Jun;36(3):424-434. doi: 10.1007/s10637-017-0514-4. Epub 2017 Sep 30.

    PubMed 28965185

Questions about this trial

What is this clinical trial studying?

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

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 7 inclusion and 12 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 15 May 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Japan. 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?

Number of participants affected by adverse events by MedDRA system organ class (SOC) and Preferred term (PT) (time frame: Up to 30 days after the last dose of study medication). 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 NCT01962532, which also lists 1 linked publication.

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 15 May 2019.

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