Overview

This trial is active, not recruiting.

Condition tumor or lymphoma
Treatments jnj-42756493: part 1, jnj-42756493: part 2, jnj-42756493: part 3, jnj-42756493: part 4
Phase phase 1
Target FGFR
Sponsor Janssen Research & Development, LLC
Start date June 2012
End date April 2017
Trial size 189 participants
Trial identifier NCT01703481, 2012-000697-34, 42756493EDI1001, CR100845

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 tumors or lymphoma.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Dose Escalation, Part 1: Participants will be enrolled in sequential cohorts to determine recommended Phase 2 doses (RP2D).
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).
(Experimental)
Dose Confirmation, Part 2: Tumor biopsy cohorts will confirm RP2D.
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).
(Experimental)
First dose expansion, Part 3: Participants with squamous non-small cell lung cancer.
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.
(Experimental)
First dose expansion, Part 3: Participants with small cell lung cancer.
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.
(Experimental)
First dose expansion, Part 3: Participants with breast cancer.
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.
(Experimental)
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).
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.
(Experimental)
Second dose expansion, Part 4: Participants with non-small cell lung cancer.
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.
(Experimental)
Second dose expansion, Part 4: Participants with solid tumors (consisting of one of the following: breast, urothelial, GBM).
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.

Primary Outcomes

Measure
Part 1: Maximum Tolerated Dose (MTD) of JNJ-42756493
time frame: Up to Part 1 Day 84 (Cycle 4, Day 21)

Secondary Outcomes

Measure
Maximum Observed Plasma Concentration (Cmax) of JNJ-42756493
time frame: Up to Part 4 Day 84 (Cycle 4, Day 21)
Minimum Observed Plasma Concentration (Cmin) of JNJ-42756493
time frame: Up to Part 4 Day 84 (Cycle 4, Day 21)
Time to Reach Maximum Observed Plasma Concentration (Tmax) of JNJ-42756493
time frame: Up to Part 4 Day 84 (Cycle 4, Day 21)
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau)
time frame: Up to Part 4 Day 84 (Cycle 4, Day 21)
Elimination Half Life of JNJ-42756493
time frame: Up to Part 4 Day 84 (Cycle 4, Day 21)
Apparent Volume of Distribution at Steady-State (Vss) of JNJ-42756493
time frame: Up to Part 4 Day 84 (Cycle 4, Day 21)
Total Clearance of JNJ-42756493
time frame: Up to Part 4 Day 84 (Cycle 4, Day 21)
Accumulation Index (AI) of JNJ-42756493
time frame: Up to Part 4Day 84 (Cycle 4, Day 21)
Number of Participants With Objective Tumor Response
time frame: Up to Part 4 Day 84 (Cycle 4, Day 21)
Progression Free Survival (PFS)
time frame: Up to Part 4 Day 84 (Cycle 4, Day 21)
Duration of Objective Response
time frame: Up to Part 4 Day 84
Number of Participants With an Adverse Event
time frame: Up to Part 4 Day 84 (Cycle 4, Day 21)

Eligibility Criteria

Male or female participants at least 18 years old.

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)

Additional Information

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
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.
Trial information was received from ClinicalTrials.gov and was last updated in December 2016.
Information provided to ClinicalTrials.gov by Janssen Research & Development, LLC.