Study of PHA-848125AC in Adult Patients With Advanced/Metastatic Solid Tumors

A Phase I Study of Oral PHA-848125AC Given Daily For 7 Consecutive Days Every 2 Weeks or for 4 Consecutive Days A Week for 3 Consecutive Weeks Every 4 Weeks to Adult Patients With Advanced/Metastatic Solid Tumors

The purpose of this open-label, multi center, Phase I study was to determine the safety profile of the oral compound PHA-848125AC administered according to two different schedules of administrations to advanced/metastatic solid tumor patients. Objectives of the study were to determine the maximum tolerated dose and the dose that can be recommended for Phase II investigations.

Study Overview

• Status: Completed
• Conditions: Solid Tumour
• Intervention / Treatment: Drug: PHA-848125AC

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Scottsdale Clinical Research Institute
  • Maryland
    • Baltiomore, Maryland, United States, 21212
      • The Johns Hopkins University

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:

• Signed, written IRB-approved Informed Consent
• Histologically or cytologically confirmed relapsed or refractory solid tumors for which no standard therapy exists
• ECOG (WHO) performance status 0-1
• Life expectancy of at least 3 months
• Age >=18 years
• A negative pregnancy test (if female in reproductive years)
• Acceptable liver and renal function
• Acceptable hematologic status
• 10. Previous cancer therapy is allowed with the exclusion of experimental CDK2 inhibitors. Treatment with radiation therapy, surgery, chemotherapy, or investigational therapy must be completed within one month prior to study entry
• Use of effective contraceptive methods if men and women of child producing potential
• Capability to swallow capsules intact
• Grade <=1 retinopathy

Exclusion Criteria:

• In the past 6 months: myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis
• Known brain metastases
• Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1
• Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
• Pregnant or breast feeding women
• Unwillingness or inability to comply with procedures required in this protocol
• Known infection with HIV, active hepatitis B or hepatitis C
• Diabetes mellitus uncontrolled, or with clinical evidence of diabetic retinopathy, severe peripheral vascular disease or diabetic ulcers
• Current enrollment in another clinical trial
• Patients who have exhibited allergic reactions to a similar structural compound, biological agent, or formulation (lactose intolerance)
• Previous history or current presence of neurological disorders, including epilepsy (although controlled by anticonvulsant therapy), Parkinson's disease, multiple sclerosis, stroke and cerebellar injury
• Gastrointestinal disease (e.g. Crohn's disease, ulcerative colitis, or short gut syndrome) that would impact on drug absorption
• Chronic/intensive use of antacid or H2 receptor antagonists
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study or could compromise protocol objectives in the opinion of the investigator and/or the sponsor.

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: Dose-escalation	Drug: PHA-848125AC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Determination of Dose Limiting Toxicities and Maximum Tolerated Dose	First cycle

Secondary Outcome Measures

Outcome Measure	Time Frame
Assessment of Adverse Events (based on CTCAE version 3.0)	All cycles
Evaluation of pharmacokinetics: plasma concentrations at different times after dosing and related assessment of conventional pharmacokinetic parameters	First 2 cycles

Collaborators and Investigators

• Sponsor: Nerviano Medical Sciences
• Investigators: Principal Investigator: Daniel Von Hoff, MD, Scottsdale Clinical Research Institute, Scottsdale AZ, USA; Principal Investigator: Manuel Hidalgo, MD, The Johns Hopkins University, Baltimore MD, USA; Principal Investigator: Daniel Laheru, MD, The Johns Hopkins University, Baltimore MD, USA

Study record dates

Study Major Dates

• Study Start: April 1, 2006
• Primary Completion (Actual): May 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: February 17, 2011
• First Submitted That Met QC Criteria: February 18, 2011
• First Posted (Estimate): February 21, 2011

Study Record Updates

• Last Update Posted (Estimate): February 21, 2011
• Last Update Submitted That Met QC Criteria: February 18, 2011
• Last Verified: February 1, 2011

More Information

Terms related to this study

• Keywords: advanced/metastatic solid tumors
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: CDKO-125a-001