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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Janssen Research & Development, LLC
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01962532
First received: July 26, 2013
Last updated: July 14, 2014
Last verified: July 2014
  Purpose

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


Condition Intervention Phase
Neoplasms
Lymphoma
Drug: Part 1: JNJ-42756493
Drug: Part 2: JNJ-42756493
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Maximum observed plasma concentration of JNJ-42756493 [ Time Frame: Up to Part 2 Cycle 4 Day 1 ] [ Designated as safety issue: No ]
  • Minimum observed plasma concentration of JNJ-42756493 [ Time Frame: Up to Part 2 Cycle 4 Day 1 ] [ Designated as safety issue: No ]
  • Time correspondent to the maximum observed plasma concentration of JNJ-42756493 [ Time Frame: Up to Part 2 Cycle 4 Day 1 ] [ Designated as safety issue: No ]
  • Area under the plasma concentration-time curve from time 0 to 24 hours of JNJ-42756493 [ Time Frame: Up to Part 2 Cycle 4 Day 1 ] [ Designated as safety issue: No ]
  • Half-life of JNJ-42756493 [ Time Frame: Up to Part 2 Cycle 4 Day 1 ] [ Designated as safety issue: No ]
  • Apparent volume of distribution of JNJ-42756493 [ Time Frame: Up to Part 2 Cycle 4 Day 1 ] [ Designated as safety issue: No ]
  • Total clearance of drug of JNJ-42756493 [ Time Frame: Up to Part 2 Cycle 4 Day 1 ] [ Designated as safety issue: No ]
  • Accumulation index of JNJ-42756493 [ Time Frame: Up to Part 2 Cycle 4 Day 1 ] [ Designated as safety issue: No ]
  • Number of participants with complete response [ Time Frame: Up to Part 2 Day 84 (Cycle 4, Day 21) ] [ Designated as safety issue: No ]
  • Number of participants with partial response [ Time Frame: Up to Part 2 Day 84 (Cycle 4, Day 21) ] [ Designated as safety issue: No ]
  • Number of participants with stable disease [ Time Frame: Up to Part 2 Day 84 (Cycle 4, Day 21) ] [ Designated as safety issue: No ]
  • Number of participants with progressive disease [ Time Frame: Up to Part 2 Day 84 (Cycle 4, Day 21) ] [ Designated as safety issue: No ]

Estimated Enrollment: 54
Study Start Date: August 2013
Estimated Study Completion Date: April 2016
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1: Dose Escalation
Dose 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.
Drug: Part 1: JNJ-42756493
JNJ-42756493 dose escalation starting at 2 mg daily by mouth will be taken for 21-day cycles up to the maximum tolerated dose in order to determine the recommended Phase 2 dose.
Experimental: Part 2: Dose Expansion
Participants will receive the recommended Phase 2 JNJ-42756493 dose determined in Part 1. 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.
Drug: Part 2: JNJ-42756493
Recommended Phase 2 JNJ-42756493 dose determined in Part 1 administered by mouth once daily (21-day cycles).

Detailed Description:

This is an open-label (identity of assigned study drug will be known), 2-part dose-escalation study 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 administered by mouth once daily in 21-day cycles 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 54 participants will be enrolled. Participants will be required to be hospitalized after the first dose on Day 1 of Cycle 1 until Day 2 of Cycle 2. The Part 1 dose-escalation phase is designed to determine the recommended Phase 2 dose 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. In Part 2, approximately 36 participants will be treated at the recommended Phase 2 dose 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.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  • 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 at screening for women of child bearing potential

Exclusion Criteria:

  • 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 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 <50 percent as assessed by echocardiography 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 a man who plans to father a child while enrolled in this study or within 3 months after the last dose of study drug
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01962532

Contacts
Contact: Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions: JNJ.CT@sylogent.com

Locations
Japan
Recruiting
Kashiwa, Japan
Recruiting
Matsuyama, Japan
Not yet recruiting
Tokyo, Japan
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More Information

Additional Information:
No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01962532     History of Changes
Other Study ID Numbers: CR102388, 42756493GAC1001
Study First Received: July 26, 2013
Last Updated: July 14, 2014
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by Janssen Research & Development, LLC:
Neoplasms
Lymphoma
Advanced or refractory solid tumors
Advanced or refractory lymphoma
JNJ-42756493
Pharmacokinetics
Japanese
Asian
Pharmacodynamics

Additional relevant MeSH terms:
Neoplasms
Lymphoma
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on July 20, 2014