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

• Status: Completed
• Trial end date: 2008-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Multicenter, open-label, dose-ranging study in two parts: maximum tolerated dose (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:

1. Accelerated Titration Stage

2. Dose Escalation/De-Escalation Stage

3. Dose Confirmation Stage

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Astex Pharmaceuticals; Astex Pharmaceuticals, Inc.

Criteria

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 treatment.

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.