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

NCT01962532 | Completed Phase 1

• 2 other identifiers: CR10238842756493GAC1001
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Neoplasms; Lymphoma; Adenocarcinoma; Esophagogastric Junction

Keywords

Neoplasms; Lymphoma; Advanced or refractory solid tumors; Advanced or refractory lymphoma; Gastric adenocarcinoma; Gastroesophageal junctions; JNJ-42756493; Pharmacokinetics; Japanese; Asian; Pharmacodynamics

Outcome Measures

Primary Outcomes (1)

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

  Up to 30 days after the last dose of study medication

Secondary Outcomes (12)

• Maximum observed plasma concentration of JNJ-42756493

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

• Minimum observed plasma concentration of JNJ-42756493

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

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

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

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

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

• Half-life of JNJ-42756493

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

Study Arms (3)

Part 1: Dose Escalation (Daily Dosing)

EXPERIMENTAL

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. 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.

Drug: Part 1: JNJ-42756493

Part 1: Dose Escalation (Intermittent Dosing)

EXPERIMENTAL

Intermitting 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.

Drug: Part 1: JNJ-42756493

Part 2: Dose Expansion

EXPERIMENTAL

Participants 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.

Drug: Part 2: JNJ-42756493

Interventions

Part 1: JNJ-42756493 DRUG

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 1: Dose Escalation (Daily Dosing); Part 1: Dose Escalation (Intermittent Dosing)

Part 2: JNJ-42756493 DRUG

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

Part 2: Dose Expansion

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (3)

Unknown Facility

Kashiwa, Japan

Location

Unknown Facility

Matsuyama, Japan

Location

Unknown Facility

Tokyo, Japan

Location

Related Publications (1)

• 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.

  PMID: 28965185 RESULT

MeSH Terms

Conditions

Neoplasms; Lymphoma; Adenocarcinoma

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Carcinoma; Neoplasms, Glandular and Epithelial

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2013
• First Posted: October 14, 2013
• Study Start: August 21, 2013
• Primary Completion: January 28, 2016
• Study Completion: January 28, 2016
• Last Updated: May 15, 2019

Record last verified: 2019-05

Locations

JP (3)