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

This study is currently recruiting participants.
Verified April 2014 by Janssen Research & Development, LLC
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01703481
First received: March 22, 2012
Last updated: April 8, 2014
Last verified: April 2014
  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.


Condition Intervention Phase
Tumor or Lymphoma
Drug: 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:
  • Part 1: Maximum tolerated dose of JNJ-42756493 [ Time Frame: Up to Part 1 Day 84 (Cycle 4, Day 21) ] [ Designated as safety issue: No ]
    The maximum tolerated dose as determined in Part 1 of the study will be used as the recommended dose for Part 2 and Part 3.


Secondary Outcome Measures:
  • Maximum observed plasma concentration of JNJ-42756493 [ Time Frame: Up to Part 3 Day 84 (Cycle 4, Day 21) ] [ Designated as safety issue: No ]
  • Time of maximum observed plasma concentration of JNJ-42756493 [ Time Frame: Up to Part 3 Day 84 (Cycle 4, Day 21) ] [ Designated as safety issue: No ]
  • Area under the plasma concentration-time curve from time 0 to time 24 hours of JNJ-42756493 [ Time Frame: Up to Part 3 Day 84 (Cycle 4, Day 21) ] [ Designated as safety issue: No ]
  • Half life of JNJ-42756493 [ Time Frame: Up to Part 3 Day 84 (Cycle 4, Day 21) ] [ Designated as safety issue: No ]
  • Apparent volume of distribution at steady-state of JNJ-42756493 [ Time Frame: Up to Part 3 Day 84 (Cycle 4, Day 21) ] [ Designated as safety issue: No ]
  • Total clearance of JNJ-42756493 [ Time Frame: Up to Part 3 Day 84 (Cycle 4, Day 21) ] [ Designated as safety issue: No ]
  • Accumulation index of JNJ-42756493 [ Time Frame: Up to Part 3 Day 84 (Cycle 4, Day 21) ] [ Designated as safety issue: No ]
  • Number of participants with best overall response of complete response (CR) [ Time Frame: Up to Part 3 Day 84 (Cycle 4, Day 21) ] [ Designated as safety issue: No ]
    Complete response is disappearance of all target lesions for a period of at least one month. This will be considered for evaluation of objective response rate.

  • Number of participants with best overall response of partial response (PR) [ Time Frame: Up to Part 3 Day 84 (Cycle 4, Day 21) ] [ Designated as safety issue: No ]
    Partial response is at least a 30% decrease in the sum of the longest diameter of measures of target lesions. This will be considered for evaluation of objective response rate.

  • Number of participants with best overall response of stable disease (SD) [ Time Frame: Up to Part 3 Day 84 (Cycle 4, Day 21) ] [ Designated as safety issue: No ]
    Stable disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progression of disease.

  • The number of participants affected by an adverse event [ Time Frame: Up to Part 3 Day 84 (Cycle 4, Day 21) ] [ Designated as safety issue: Yes ]
  • Progression free survival [ Time Frame: Up to Part 3 Day 84 (Cycle 4, Day 21) ] [ Designated as safety issue: No ]
    Progression free survival is the time period from start of study medication till the disease progression or death, whichever occurs first.

  • Duration of objective response [ Time Frame: Up to Part 3 Day 84 ] [ Designated as safety issue: No ]
    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.

  • Number of participants with best overall response of progressive disease (PD) [ Time Frame: Up to Part 3 Day 84 (Cycle 4, Day 21) ] [ Designated as safety issue: No ]
    Progressive disease is a 20 percentage or greater increase in the sum of the longest diameter of measured lesions (target lesions), taking as reference the smallest sum of longest diameter recorded since the treatment started or the appearance of one or more new lesions


Estimated Enrollment: 260
Study Start Date: June 2012
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1
Dose Escalation Part 1 will determine recommended Phase 2 dose (RP2D)
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 dose (RP2D). Part 2: RP2D (maximum tolerated dose from Part 1) will be taken orally once daily on a continuous 21-day cycle to confirm RP2D. Part 3: RP2D will be taken orally once daily on a continuous 21-day cycle
Experimental: Part 2
Dose Confirmation Part 2 will confirm RP2D
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 dose (RP2D). Part 2: RP2D (maximum tolerated dose from Part 1) will be taken orally once daily on a continuous 21-day cycle to confirm RP2D. Part 3: RP2D will be taken orally once daily on a continuous 21-day cycle
Experimental: Part 3, Cohort A
Dose expansion Part 3. Participants with nonsmall cell lung cancer
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 dose (RP2D). Part 2: RP2D (maximum tolerated dose from Part 1) will be taken orally once daily on a continuous 21-day cycle to confirm RP2D. Part 3: RP2D will be taken orally once daily on a continuous 21-day cycle
Experimental: Part 3, Cohort B
Dose expansion Part 3. Participants with small cell lung cancer
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 dose (RP2D). Part 2: RP2D (maximum tolerated dose from Part 1) will be taken orally once daily on a continuous 21-day cycle to confirm RP2D. Part 3: RP2D will be taken orally once daily on a continuous 21-day cycle
Experimental: Part 3, Cohort C
Dose expansion Part 3. Participants with breast cancer
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 dose (RP2D). Part 2: RP2D (maximum tolerated dose from Part 1) will be taken orally once daily on a continuous 21-day cycle to confirm RP2D. Part 3: RP2D will be taken orally once daily on a continuous 21-day cycle
Experimental: Part 3, Cohort D
Dose expansion Part 3. Participants with solid tumors
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 dose (RP2D). Part 2: RP2D (maximum tolerated dose from Part 1) will be taken orally once daily on a continuous 21-day cycle to confirm RP2D. Part 3: RP2D will be taken orally once daily on a continuous 21-day cycle

Detailed Description:

This is a Phase 1 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, 3-part, dose-escalation study. Each cycle will consist of 21 days of daily continuous dosing or 28 days of intermittent dosing schedule. Part 1 is the dose-escalation phase, which will be guided by pharmacokinetics and safety. Three to 6 new participants will be enrolled in sequential cohorts (first cohort will receive the starting dose and subsequent cohorts will receive increased doses of JNJ-42756493). Enrollment in each cohort will be staggered; the second and third participant in every cohort will not be dosed until the first participant in that cohort is beyond Day 7 of Cycle 1. If no dose-limiting toxicities (DLTs) have been observed during the first week of Cycle 1 in the first participant, the second and third participant in the cohort will initiate treatment. After the last participants in each cohort completes Cycle 1 (DLT observation period of 21 days of treatment), the Safety Evaluation Team (SET) will evaluate the safety for DLT determination and the pharmacokinetic data and make the decision whether to escalate the dose in a new cohort of 3 to 6 new participants. Dose escalation will halt when the maximum tolerated dose (MTD) or when the plasma concentrations exceed the predefined cardiovascular threshold. The total number of participants to be enrolled in Part 1 will depend on the dose level at which the DLT will be achieved. Part 2 is the Dose Confirmation Phase, which consists of 1 biopsy cohort. The study drug will be administered once daily on a continuous 21 day cycle at the RP2D. Approximately 10 to 20 participants will be enrolled for treatment at the RP2D. In the Part 2 biopsy cohort, tumor biopsies will be mandatory at pretreatment and during treatment (Day 1 of Cycle 2) until pretreatment/post-treatment biopsy pairs are collected for at least 10 participants. Part 3 is the Dose Expansion Phase, which consists of 4 expansion cohorts (Cohorts A, B, C, and D). In this cohort, study drug will be administered once daily on a continuous 21-day cycle. Up to 15 subjects for each cohort will be enrolled before the interim analysis and up to 30 additional subjects may be enrolled for treatment at the RP2D to evaluate clinical responses. The study will take approximately 36 months to complete.

  Eligibility

Ages Eligible for Study:   18 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 (Part 1); any type of advanced or refractory solid malignancy (excluding lymphoma) that is metastatic or unresectable and participants must be amenable to pre- and post-treatment biopsies (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)
  • Eastern Cooperative Oncology Group performance status score 0 or 1
  • Adequate bone marrow, liver, and renal function within the 7 days prior to Day 1 of Cycle 1 of study drug
  • Serum electrolyte levels (magnesium, potassium) within 0.85 to 1.25 x institutional normal limits (within 7 days prior to Day 1 of Cycle 1)

Exclusion Criteria:

  • Chemotherapy, targeted therapies, radiotherapy, immunotherapy, or treatment with an investigational anticancer agent within 3 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
  • Persistent calcium or phosphate greater than upper limit of normal during screening (within 7 days of treatment) and despite medical management of calcium or phosphate levels
  • Participants taking medications known to have a significant risk of causing QTc prolongation and Torsades de Pointes or known as strong CYP3A inhibitors or inducers
  • Left ventricular ejection fraction (LVEF) less than 48 percentage as assessed by echocardiography 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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01703481

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

  Show 30 Study Locations
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: NCT01703481     History of Changes
Other Study ID Numbers: CR100845, 42756493EDI1001, 2012-000697-34
Study First Received: March 22, 2012
Last Updated: April 8, 2014
Health Authority: United States: Food and Drug Administration
Spain: Spanish Agency of Medicines
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

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

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

ClinicalTrials.gov processed this record on April 17, 2014