MDACC Study Summary 2007-0088

Study Summary
No. 2007-0088:.......Colorectum; Melanoma......Kevin B. Kim......Melanoma Medical Oncology

Study Summary Title



Study Summary Number:	2007-0088

Study Title:	A Study To Assess Safety, Pharmacokinetics, and Pharmacodynamics of PLX4032 in Patients with Solid Tumors

Physician

New Patient Referral



Name:	Kevin B. Kim	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Melanoma Medical Oncology	Referring MD Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Phone:	713-792-2921 Contact us about clinical trials

General Information



Disease Group:	Colorectum Melanoma	Supported By:	Roche, 340 Kingsland Street, Nutley, New Jersey, USA: Linda Burdette, Ph.D. Phone 973-235-4578; Fax: 973-562-3700

Phase of Study:	Phase I	Return Visit:	Days 1, 2 8, 15, 16 and 29 and every 4 weeks afterwards

Treatment Agents:	PLX-4032	Home Care:	N/A

Treatment Loc:	Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions

Estimated Length of Stay in Houston:	N/A


Description/ Intervention:	The goals of this clinical research study are find the highest tolerable dose of PLX4032 that can be given to patients with cancer of the colon or rectum, learn the safety of the study drug, and perform pharmacokinetic (PK) testing of the drug. PK testing measures the amount of a drug in the body at different time points.

Study Objectives / Outcomes

1. The primary objective for the dose escalation phase of this study is to evaluate the safety and PK of PLX4032 in patients with solid tumors

2. The primary objective for the Extension cohorts is to evaluate the objective tumor response (including overall response rate, duration of response, and progression free survival), safety, and PK of PLX4032 in patients with advanced melanoma and metastatic colorectal carcinoma with confirmed V600E+BRAF mutation status.

Secondary Objectives

1. The secondary objectives are a) to measure the pharmacodynamic activity of PLX4032 via inhibition of pMEK and pERK activity in tumor biopsy samples in the paired biopsy cohorts, b) to measure the pharmacodynamic activity of PLX4032 via inhibition of 18FDG update in the melanoma Extension cohort, and c) access exploratory biomarkers in both Extension cohorts, d) to assess the relative bioavailability of the 80 mg capsules, 120 mg capsules, and 240 mg tablets and e) to conduct food-effect evaluation in a subset of patients receiving the 240 mg tablets at the 960 mg bid dose level.

Study Status Information



Study Activation / Registration Date:	08/24/2007

IRB Review and Approval Date:	08/24/2007

Study Type:	Phase I

Recruitment Status:	Open

Projected Accrual:	140

Enrollment Eligibility

If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:

1) Willing and able to provide written informed consent prior to any study-related procedures and to comply with all study requirements

2) 2. Male or female patients >/= 18 years old with solid tumors confirmed histologically, whose tumors are refractory to standard therapy, or for whom standard or curative therapy does not exist or is not considered appropriate by the investigator

3) Women of child-bearing potential must have a negative pregnancy test within 21 days of initiation of dosing and must agree to use an acceptable method of birth control from the time of the negative pregnancy test up to 30 days after the last dose of study drug. Women of non-childbearing potential may be included if they are either surgically sterile or have been postmenopausal for >/= 1 year. Fertile men must also agree to use an acceptable method of birth control while on study drug.

4) Previous chemotherapy, immunotherapy, or radiation therapy must have been completed at least 2 weeks prior to starting PLX4032 therapy, and all associated toxicity must be resolved (to </= Grade 1 or Baseline) prior to administration of PLX4032

5) Patients from whom paired melanoma biopsies are planned must have a V600E+ BRAF mutation confirmed prior to the administration of PLX4032

6) Patients in the Phase 1 Extension cohorts (melanoma or adenocarcinoma of the colon or rectum) must have both a V600E+ BRAF mutation and measurable disease (by RECIST V 1.0 criteria) prior to the administration of PLX4032. All patients enrolled must provide archival or fresh melanoma tumor biopsy for confirmation of V600E+ BRAF mutation status by TaqMan assay

7) ECOG performance status 0 or 1

8) Life expectancy greater than or equal to 3 months

9) Adequate hematologic, hepatic, and renal function (absolute neutrophil count >/= 1.5 X 109/L, Hgb > 9 g/dL, platelet count >/= 100 X 109/L, AST/ALT </= 2.5X ULN or < 5x ULN in the presence of liver metastases, albumin >/= 3 g/dL, creatinine </= 1.5 X ULN or calculated CrCl>60 mL/min using Cockroft-Gault formula)

Exclusion Criteria:

1) Known hypersensitivity or idiosyncratic reaction to PLX4032 or related compounds

2) For the Phase 1 Extension cohort, previous treatment with BRAF or MEK inhibitor

3) Known brain metastases that are progressing or have been documented to be stable for less than 3 months or for which systemic corticosteroids are required

4) Investigational drug use within 28 days of the first dose of PLX4032

5) Uncontrolled intercurrent illness

6) Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate absorption

7) Mean QTc (from triplicate ECG's) greater than or equal to 500 msec at Baseline

8) The presence of a medical or psychiatric condition which, in the opinion of the investigator, makes the patient inappropriate for inclusion in this study.

Links

Registration Number: NCT00405587
Study Information on Clinical Trials Registry (clinicaltrials.gov)