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Safety Study to Determine the Maximum Tolerated Dose, Pharmacokinetics and Pharmacodynamics of Oral MP470, a Multitargeted Tyrosine Kinase Inhibitor, in Patients With Solid Malignancies

Phase 1
18 Years
70 Years
Not Enrolling
Solid Tumors

Thank you

Trial Information

Safety Study to Determine the Maximum Tolerated Dose, Pharmacokinetics and Pharmacodynamics of Oral MP470, a Multitargeted Tyrosine Kinase Inhibitor, in Patients With Solid Malignancies

Multicenter, open-label, dose-ranging study in two parts: MTD Segment (the first 28-day
course of MP 470) followed by Long-Term Safety Segment

MTD Segment: follows standard oncology phase-I design; within-patient dose level adjustments
prohibited; each patient participates in one of three stages:

Accelerated Titration Stage: 1 patient per dose level; first patient receives MP 470 at 100
mg/day; subsequent patients assigned higher dose levels based on modified Fibonacci
sequence; stage stops when any first-course DLT is observed or when grade-2 or greater MP
470-related toxicity is observed at 2 dose levels; dosing next patient prohibited until
previous patient's MTD-Segment result is confirmed Dose Escalation/De-Escalation Stage: 3
patients per cohort; two additional patients enrolled to receive last dose level studied
during Accelerated Titration Stage (first 3-patient cohort); subsequent 3-patient cohorts
assigned dose level conditional on number of patients with first-course DLT in previous
cohort; new cohorts enrolled until MTD is defined; dosing next cohort prohibited until
previous cohort's MTD-Segment results are confirmed Dose Confirmation Stage: an additional
6-10 patients enrolled to receive MP 470 at the established MTD; patient accrual stops
following Dose Confirmation Long-Term Safety Segment: patients continue receiving 28-day
courses of MP 470 until experiencing unmanageable toxicity or disease progression;
within-patient dose level adjustments based on toxicity; DLT during preceding 28-day course
mandates one-level dose reduction; one-level dose increase possible in absence of grade-3 or
greater MP 470-related AEs during preceding 28-day course

Inclusion Criteria:

1. The patient has a histological or cytological diagnosis of unresectable or metastatic
solid-tumor cancer that is refractory to standard therapies or for which no standard
therapy exists. Patients with refractory lymphoma (Hodgkin's or NHL) are also
permitted to participate.

2. The patient must read, understand and sign the IRB-approved informed consent form
(ICF) confirming his or her willingness to participate in this trial.

3. The patient is willing and able to participate in all of the required evaluations and
procedures described in this study protocol, including swallowing MP 470 capsules.

4. The patient is at least 18 years old.

5. The patient is capable of fasting for 6 hours.

6. The patient has Karnofsky Performance Status ≥ 70 (see Appendix 5).

7. The patient has adequate bone marrow function evidenced, at minimum, by Hgb ≥ 9 g/dL,
ANC ≥ 1.5 x 109/L and platelet count ≥ 100 x 109/L.

8. The patient has normal renal and hepatic function evidenced, at minimum, by total
serum bilirubin ≤ 2 mg/dL; AST and ALT ≤ 2.5 x ULN (upper limit of normal for the
clinical laboratory), but ≤ 5 x ULN is acceptable if due to hepatic metastases; serum
albumin ≥ 2 g/dL; and serum creatinine ≤ 2 mg/dL.

9. The patient has normal cardiac function in the opinion of the investigator and
supported by left ventricular ejection fraction (LVEF) 50% or greater on the
screening echocardiogram, no significant abnormalities on the screening ECG (eg, left
bundle branch block, III degree AV block, acute myocardial infarction or QTc interval
> 450 msec) and no history of additional risk factors for torsade de pointes (eg,
heart failure, hypokalemia or family history of Long QT Syndrome).

10. The patient has recuperated from any prior surgical procedures including at least 4
weeks rest since a major surgery.

11. The patient does not have childbearing potential or has had a negative serum
pregnancy test within the past 14 days.

12. The patient does not have reproductive potential or has agreed to use and will use an
approved method of contraception during the study and for 3 months following the last
dose of MP 470.

13. The patient is not lactating.

Exclusion Criteria:

1. The patient has a life-threatening illness, medical condition or organ system
dysfunction which, in the investigator's opinion, could compromise the patient's
safety, interfere with the absorption or metabolism of oral MP 470, or put the study
outcomes at risk.

2. The patient has any serious, uncontrolled active infection that requires systemic

3. The patient has a history of significant cardiovascular disease such as uncontrolled
or symptomatic arrhythmias, congestive heart failure and/or myocardial infarction.

4. The patient has received any anticancer agent(s) within the past 3 weeks, including
investigational agents, chemotherapy (6 weeks for nitrosoureas or mitomycin),
immunotherapy, biologic or hormonal therapy other than LHRH agonists.

5. The patient has received radiation therapy within the past 4 weeks.

6. The patient has a grade-2 or more severe toxicity (other than alopecia) continuing
from prior anticancer therapy.

7. The patient has active CNS metastases (primary brain tumors are permitted).

8. The patient requires treatment with immunosuppressive agents other than
corticosteroids that have been at stable doses for at least 2 weeks.

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety and tolerability

Outcome Time Frame:

6 months

Safety Issue:



United States: Food and Drug Administration

Study ID:




Start Date:

May 2007

Completion Date:

December 2008

Related Keywords:

  • Solid Tumors
  • MP470
  • MP-470
  • SuperGen
  • Tyrosine
  • Kinase
  • Inhibitor
  • Solid Malignancies
  • Oncology
  • Neoplasms



Translation Genomics Research Institute (TGen)/Scottsdale Clin.ResearcScottsdale, Arizona  85258
So. Texas Accelerated Research Therapeutics-STARTSan Antonio, Texas  78229