Roche trials database

Trial information

A Pharmacokinetic Study of RO5185426 in Combination With a Drug Cocktail in Patients With Metastatic Melanoma

Status:

Active, not recruiting

Protocol number:

NP22676

Sponsor:

Hoffmann-La Roche

Company division:

Pharmaceutical

Official Scientific Title:

A multi-center, open-label, study to investigate the pharmacokinetic interaction of RO5185426 with a "cocktail" of five probe drugs for CYP450 dependent metabolism in patients with previously treated and untreated metastatic melanoma

Brief summary:

This open-label single-arm study will evaluate the effect of RO5185426 [RG7204; PLEXXIKON: PLX4032] on the pharmacokinetics of five CYP450 substrates (caffeine, warfarin + vitamin K, omeprazole, dextromethorphan, midazolam) administered as a drug cocktail to patients with metastatic melanoma. The study will also evaluate efficacy and safety of RO5185426. On day 1, patients will receive the drug cocktail. On days 6 to 19, patients will receive RO5185426 twice daily. On day 20, patients will receive RO5185426 and the drug cocktail and on days 21 to 25, patients will receive RO5185426. Assessments will be made at regular intervals during the dosing periods and at follow-up. Patients may continue on study treatment (RO5185426) until the development of progressive disease or unacceptable toxicity. Target sample size <50. Target sample size is 22.

Study phase:

I

Study type:

Interventional; Treatment; Non-randomized; Open label; Uncontrolled; Parallel; Pharmacokinetics study

Conditions:

• Malignant Melanoma

Primary outcome:

1. Pharmacokinetics: blood concentration levels of RO5185426 and of the 5 drugs of the drug cocktail and their metabolites Time frame: Multiple sampling, days 1-25

Key secondary outcomes:

1. Efficacy: best overall response rate, duration of response, time to response, progression-free survival, overall survival Time frame: Tumour assessment on day 28 and every 8 weeks thereafter
2. Safety and tolerability: AEs, laboratory parameters Time frame: Throughout study, laboratory assessments on days 1, 2, 5, 18, 20, 22 and every 1-2 cycles thereafter

Inclusion criteria:

• Adult patient >/= 18 years of age
• Malignant melanoma (Stage IV, AJCC)
• Patients who are treatment-naive or have received prior systemic treatments for metastatic melanoma. Time elapsed between previous treatment for metastatic disease and first administration of study drug must be at least 28 days
• Positive tested for BRAF mutation
• Patients must not be poor metabolizers of CYP450 enzymes 2C9, 2C19, or 2D6 as determined by genotyping
• Measurable disease by RECIST criteria
• Negative pregnancy test; for fertile men and women, effective contraception during treatment and for 6 months after completion

Exclusion criteria:

• Active CNS lesions on CT/MRI within 28 days prior to enrollment
• History of known spinal cord compression, or carcinomatous meningitis
• Severe cardiovascular disease within 6 months prior to study

Gender:

Males or Females

Age limits:

Min: 18 years Max: N/A N/A

Accepts healthy volunteers:

No

Anticipated start date:

November, 2009

Trial registration date:

06.10.2009

Date last updated:

10.06.2013

This trial was conducted at the following locations:

UNITED STATES

• LOS ANGELES, CA
• Boston, MA
• Nashville, TN
• Dallas, TX

Link to trial result