A Safety and Dose-finding Study of JNJ-38877605 in Patients With Advanced or Refractory Solid Tumors.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00651365
Recruitment Status : Terminated (Early termination due to increase in serum creatinine levels and minimal PD activity.)
First Posted : April 2, 2008
Last Update Posted : March 8, 2013
Ortho Biotech, Inc.
Information provided by:
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Brief Summary:
This purpose of the study is to determine what dose of JNJ-38877605 is safe and if JNJ-38877605 has any effect in patients with advanced or refractory solid tumors for which there are not alternative therapies.

Condition or disease Intervention/treatment Phase
Neoplasms Drug: JNJ-38877605 Phase 1

Detailed Description:
JNJ-38877605 is a new drug being developed for the treatment of cancer. It is an inhibitor of mesenchymal epithelial transition (Met) kinase, a substance identified in many cancers. This is the first study in which JNJ-38877605 will be administered in man. This research study is being carried out to determine the highest dose of JNJ-38877605 that patients with advanced or refractory solid tumors can tolerate. The study will also test the safety of JNJ-38877605. Safety evaluations will include an assessment of adverse events, clinical laboratory data, electrocardiograms, vital signs measurements, physical examination findings, and Eastern Oncology Cooperative Group (ECOG) performance status. In some patients the effect of food on how the drug is absorbed will also be studied. Throughout the study, treatment will be given in cycles which will be 21 days long and the study drug will be taken once a day. The number of cycles will depend on the effects the drug has on the patient and whether the patient benefits from the treatment. The design of a cycle may be adjusted during the course of the study, so that the cycle is shorter or longer, or includes some days when the patient does not receive treatment (a pause = intermittent treatment). It is also possible the drug will be taken more than once a day. In case of any changes to the drug administration schedule, the schedule and the timing of visits and blood/urine tests may be adapted accordingly, without increasing their number. During the first treatment cycle, 2 or 3 overnight stays in the hospital are required and visits to the hospital during cycles 1, 2, 3, and 4 may take up to 12 hours after the morning dose. From cycle 5 onwards, there is a daytime visit only once every cycle, and these usually take up less time. Patients are informed about the current visit schedule at enrollment and throughout the study. The dose of JNJ-38877605 administered in the study will start low and will be increased during the study. The amount of study drug taken each day by an individual patient depends on when the patient enrolls in the study. If a group of patients does not have severe side effects, the next group of patients will get a higher dose. The dose will increase until some patients have severe side effects. The dose will then be decreased and 3 to 6 patients will receive the highest amount of drug where severe side effects were not observed. The amount of JNJ-38877605 in the patient's blood will be measured and the study will also look at the effect of the drug on the disease. The patient may continue treatment as long as there is benefit as assessed by the response assessments throughout the study and the patient has no unacceptable side effects. A follow-up visit for each patient will take place within 14 days after the patient takes the last dose of JNJ-38877605. JNJ-38877605 is provided in 10, 50, and 100 mg capsules for oral use. JNJ-38877605 will initially be administered once a day orally although the administration schedule may be modified at later stages in the study. JNJ-38877605 will be provided as a take-home formulation in childproof high-density polyethylene bottles.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 14 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study to Determine the Safety, Pharmacokinetics and Pharmacodynamics of the Selective Met Inhibitor JNJ-38877605 in Subjects With Advanced or Refractory Solid Tumors
Study Start Date : February 2008
Actual Primary Completion Date : December 2010
Actual Study Completion Date : December 2010

Arm Intervention/treatment
Experimental: 001 Drug: JNJ-38877605

Primary Outcome Measures :
  1. Determine the safety and tolerability of JNJ-38877605 by assessment of the adverse event profile (throughout the study), dose-limiting toxicity (Cycle 1), and the maximum tolerated dose.

Secondary Outcome Measures :
  1. Determine the pharmacokinetic profile of JNJ-38877605 and its metabolite, JNJ-40434654 and to investigate the potential impact of food on the PK profile (Cycle 1). Explore the pharmacodynamic effects and measure anti-tumor activity of JNJ-38877605.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Confirmed advanced or refractory solid tumor no longer eligible for approved therapies
  • Eastern Cooperative Oncology Group performance status test score of <=2
  • Must meet protocol lab criteria which will include lab assessment of adequate bone marrow function, liver function, and renal function.

Exclusion Criteria:

  • Any medical condition that requires wound healing during the study (for example chronic leg ulcers, gastric ulcer disease, or expected major surgery)
  • Major surgery within 3 weeks before enrollment
  • Decreased or deficient coagulability of blood (for example genetic defects such as protein Z deficiency) or compliance problems in subjects required to take anticoagulants (e.g., coumarin derivates, acetylsalicylic acid) which could result in decreased or deficient coagulability
  • Chemotherapy (for nitrosoureas and mitomycin C within 6 weeks), radiotherapy, immunotherapy, or any other investigational agent within 3 weeks before study drug administration
  • antibody therapy within 3 months before administration of JNJ-38877605
  • brain metastases
  • History of uncontrolled heart disease within 12 months before enrollment or any protocol-defined cardiovascular abnormalities
  • Patients with hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00651365

Sponsors and Collaborators
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Ortho Biotech, Inc.
Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Responsible Party: Director, Clinical Scientist, Johnson & Johnson Pharmaceutical Research and Development, L.L.C. Identifier: NCT00651365     History of Changes
Other Study ID Numbers: CR014644
CR014644 ( Other Identifier: Johnson & Johnson Pharmaceutical Research & Development, L.L.C. )
First Posted: April 2, 2008    Key Record Dates
Last Update Posted: March 8, 2013
Last Verified: March 2013

Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:
Advanced solid tumors
Refractory solid tumor
Antineoplastic protocol
Drug therapy
Met inhibitor