To Determine the Maximum Tolerated Dose of Oral CEP-37440 in Patients With Advanced or Metastatic Solid Tumors

An Open-Label Study to Determine the Maximum Tolerated Dose of Oral CEP-37440 Administered as a Single Agent in Patients With Advanced or Metastatic Solid Tumors

The primary objective is to determine the maximum tolerated dose (MTD), safety, and tolerability of oral CEP-37440 administered daily to patients with advanced or metastatic solid tumors.

Study Overview

• Status: Completed
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: CEP-37440

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States
      • Teva Investigational Site 10689
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States
      • Teva Investigational Site 10687
  • Texas
    • San Antonio, Texas, United States
      • Teva Investigational Site 10686

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must have histologic or cytologic evidence of a solid neoplasm for which no standard therapy is available, or have progressed despite standard therapy, or are intolerant to standard therapy.
• Patients must have evidence of recurrent, locally advanced, or metastatic disease.
• Patients can either have had no prior anticancer therapy, multiple lines of either prior chemotherapy/biologic therapy/experimental therapy or, if the patient has anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC), prior crizotinib.
• Patients must have a predicted life expectancy of more than 3 months.
• Patients must have presence of at least 1 lesion that is measurable or evaluable using RECIST v1.1.
• Patients must have an ECOG performance score of 0, 1, or 2.
• Patients with central nervous system (CNS) metastases will be allowed on this study. Patients may have received surgical and/or radiation treatment. The metastases must be neurologically stable, on or off corticosteroids. Patients can have low level, asymptomatic brain lesions that do not require surgical/radiation intervention acutely. Patients with symptomatic lesions with impending neurologic compromise should be appropriately treated with high dose steroids/radiation and may be re-evaluated for this study when neurologically stable.
• Patients must have completed any prior anticancer treatment and must have recovered from any acute toxicities. The period between the last dose of prior treatment and the first dose of study drug treatment must be at least 1 week for radiotherapy and at least 2 to 3 weeks for all other modalities of therapy including chemotherapy, monoclonal antibody therapy, immunotherapy, other investigational drugs, or other kinase inhibitors.
• Other criteria apply.

Exclusion Criteria:

• The patient has ongoing or active infection requiring parenteral antibiotics.
• The patient has uncontrolled hypertension despite adequate therapy (ie, systolic blood pressure higher than 150 mm Hg or diastolic blood pressure higher than 90 mm Hg found on 2 separate occasions separated by 1 week).
• The patient has uncontrolled diabetes mellitus (despite therapeutic intervention) and occurrence of more than 2 episodes of ketoacidosis in the 12 months prior to the first dose of study drug.
• The patient has an active second malignancy other than curatively resected basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ carcinoma of the cervix, or other cancers for which they are treated with curative intent, and no known active disease in the 3 years prior to enrollment.
• The patient has a primary brain tumor. Patients may have brain metastases from another primary site.
• The patient has QTcF interval greater than 450 msec, has a known history of QTcF prolongation, is taking medications known to prolong QTcF, or has a history of torsade de pointes.
• The patient has a prior ALK-inhibitor-related toxicity or any other prior therapy-related acute toxicity that has not resolved prior to the first dose of study drug.
• Other criteria apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CEP-37440	Drug: CEP-37440; CEP-37440 will be supplied as 25 mg and 100 mg capsules and will be orally administrated daily. Patients will be enrolled sequentially in dose escalating cohorts to receive CEP-37440 until a maximum tolerated dose has been defined.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Response Evaluation Criteria in Solid Tumors (RECIST v1.1)	8 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Response (TTR)	The time interval from the date of first dose to the first documented response (complete or partial response)	8 months
Number of participants with adverse events		From signing of the informed consent to the end of the follow-up visit (approximately Month 10)
Time to Progression (TTP)	The time interval from date of first dose to first documented disease progression	8 months
Progression-free Survival (PFS)	Time interval from date of first does to first documented disease progression or death from any cause (whichever occurs first)	10 months
Time to New Metastases (TTNM)	Time interval from date of first dose to first documented new metastatic lesion not reported at baseline	8 months

Collaborators and Investigators

• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: August 12, 2013
• First Submitted That Met QC Criteria: August 12, 2013
• First Posted (Estimate): August 14, 2013

Study Record Updates

• Last Update Posted (Actual): November 12, 2021
• Last Update Submitted That Met QC Criteria: November 5, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: Advanced solid tumors; CEP-37440; Metastatic solid tumors
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: C37440/1108