Phase I Dose Escalation Study to Determine the Safety and Pharmacokinetics of MSX-122 Administered Orally in Patients With Refractory Metastatic or Locally Advanced Solid Tumors

Metastatix, Inc.1 site in 1 country27 target enrollmentNovember 2007

ConditionsSolid Tumors

InterventionsMSX-122

DrugsMSX-122

Overview

Phase: Phase 1
Intervention: MSX-122
Conditions: Solid Tumors
Sponsor: Metastatix, Inc.
Enrollment: 27
Locations: 1
Primary Endpoint: Determine the maximum tolerated dose (MTD) and the recommended Phase II dose(s) and schedule of MSX-122
Status: Suspended
Last Updated: 18 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

Primary Objectives:

To determine the maximum tolerated dose (MTD) and the recommended Phase II dose(s) and schedule of MSX-122
To characterize the dose limiting toxicities (DLTs) and determine the overall safety and tolerability of MSX-122

Secondary Objectives:

To determine the pharmacokinetics and pharmacodynamics of orally administered MSX-122
To evaluate the preliminary evidence for anti-tumor activity of MSX-122
To perform correlative studies to elucidate signaling pathways involved in CXCR4 activation in blood and optional tissue specimens by IHC (immunohistochemistry) and RPPA (reverse phase protein microarrays)

Registry

clinicaltrials.gov

Start Date

November 2007

End Date

March 2009

Last Updated

18 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Metastatix, Inc.

Eligibility Criteria

Inclusion Criteria

•Patients with pathologically confirmed advanced malignancy that is metastatic or unresectable and which is refractory to standard therapy or for which there is no standard therapy that provides benefit
•Measurable or non-measurable disease at baseline
•At least four weeks since the last dose of prior chemotherapy, treatment with biologic agents, radiation therapy or investigational agents
•Patients must have recovered from the adverse effects of prior therapy at the time of enrollment to a grade one or less(excluding alopecia)
•Patient will not be treated with any other chemotherapy, immunotherapy, radiotherapy or investigational drug while enrolled on this protocol
•Age \>/= 18 year, male or female patients
•Eastern Cooperative Oncology Group (ECOG) performance status 0,1, or 2
•Life expectancy of greater than 3 months following study entry
•Adequate renal function, defined by serum creatinine less than or equal to 1.5 x ULN
•Adequate hepatic function as defined by aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels \</= to 2.5 x ULN and total bilirubin \</= to 1.5 x ULN. In the presence of liver metastasis, adequate hepatic function is defined as ALT and AST \</= 5 x ULN and total bilirubin \</= 3 x ULN. Alkaline phosphatase levels less than or equal to 2.5 x ULN. In the presence of extensive bone metastases, alkaline phosphatase is defined as less than or equal to 5 x ULN

Exclusion Criteria

•Patients with uncontrolled concurrent illness, including but not limited to: ongoing or active infection; uncontrolled arterial hypertension (\>/= 140/90 mm of mercury on medications); uncontrolled endocrine diseases (e.g. diabetes mellitus, hypothyroidism or hyperthyroidism, adrenal disorder); altered mental status or psychiatric illness/social situations that would limit compliance with study requirements and/or obscure study results
•Patients with a history of a cardiovascular illness including but not confined to: CHF (grade III or IV NYHA); a history of angina pectoris within the previous year; history of any cardiac arrhythmia; QTc prolongation as determined by Bazett's formula and defined as QTc interval \>480 msec (including patients on medication which may prolong QTc), or history of myocardial infarction within one year of study enrollment
•Patients with leukemias or myelodysplastic syndrome (MDS)
•Immunocompromised patients, including subjects known to be infected by human immunodeficiency virus (HIV)
•Patients with a history of autologous BMT within the previous five years. Patients with organ transplants, or allogeneic BMT will not be eligible for the study
•Patients with untreated or uncontrolled brain metastasis, or patients with leptomeningeal disease
•Patients unable to swallow oral medications or with pre-existing gastrointestinal disorders that might interfere with proper absorption of the oral drugs (e.g. WDHA syndrome, carcinoid syndromes, diarrhea due to infections, malabsorption syndromes secondary to surgery or chemotherapy).
•Patients with a history of major surgery within 28 days of first receipt of study drug
•Nursing or pregnant women
•Patients with any other diseases, metabolic dysfunction, physical examination finding or clinical laboratory finding that in the opinion of the investigator, contraindicates the use of an investigational drug, or that may render the patient at excessively high risk for treatment complications

Arms & Interventions

1

MSX-122

Intervention: MSX-122

Outcomes

Primary Outcomes

Determine the maximum tolerated dose (MTD) and the recommended Phase II dose(s) and schedule of MSX-122

Time Frame: 12 Months Estimated

Characterize the dose limiting toxicities (DLTs) and determine the overall safety and tolerability of MSX-122

Time Frame: 12 Months Estimated

Secondary Outcomes

Determine the pharmacokinetics and pharmacodynamics of orally administered MSX-122(12 Months Estimated)
Evaluate the preliminary evidence for anti-tumor activity of MSX-122(12 Months Estimated)
Perform correlative studies to elucidate signaling pathways involved in CXCR4 activation in blood and optional tissue specimens by IHC (immunohistochemistry) and RPPA (reverse phase protein microarrays)(12 Months Estimated)