Clinical trial NCT01300468: Study of PHA-848125AC in Adult Patients With Advanced/Metastatic Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumour
Keywords: advanced/metastatic solid tumors
Lead sponsor: Nerviano Medical Sciences
Sponsor class: INDUSTRY
First posted: 2011-02-21
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Determination of Dose Limiting Toxicities and Maximum Tolerated Dose
timeFrame: First cycle
Secondary outcomes:
measure: Assessment of Adverse Events (based on CTCAE version 3.0)
timeFrame: All cycles
measure: Evaluation of pharmacokinetics: plasma concentrations at different times after dosing and related assessment of conventional pharmacokinetic parameters
timeFrame: First 2 cycles
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Scottsdale Clinical Research Institute
state: Arizona
city: Baltiomore
country: United States
facility: The Johns Hopkins University
state: Maryland
Study officials:
affiliation: Scottsdale Clinical Research Institute, Scottsdale AZ, USA
name: Daniel Von Hoff, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Johns Hopkins University, Baltimore MD, USA
name: Manuel Hidalgo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Johns Hopkins University, Baltimore MD, USA
name: Daniel Laheru, MD
role: PRINCIPAL_INVESTIGATOR
References: