A Pharmacokinetic Study of RO5185426 in Combination With a Drug Cocktail in Patients With Metastatic Melanoma - Full Text View

Purpose

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.

Condition	Intervention	Phase
Malignant Melanoma	Drug: RO5185426 Drug: Drug cocktail	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official 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

Resource links provided by NLM:

MedlinePlus related topics: Melanoma

U.S. FDA Resources

Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:

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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]

Enrollment:	22
Study Start Date:	November 2009
Estimated Study Completion Date:	August 2013
Estimated Primary Completion Date:	August 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Single arm	Drug: RO5185426 960 mg orally twice daily Drug: Drug cocktail Drug cocktail (caffeine, warfarin + vitamin K, omeprazole, dextromethorphan, midazolam) orally once daily, day 1 and day 20

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01001299

Locations

United States, California

Los Angeles, California, United States, 90095
United States, Massachusetts

Boston, Massachusetts, United States, 02114

Boston, Massachusetts, United States, 02215
United States, Tennessee

Nashville, Tennessee, United States, 37232
United States, Texas

Dallas, Texas, United States, 75246

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

Study Director:

Clinical Trials

Hoffmann-La Roche

More Information

No publications provided by Hoffmann-La Roche

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Su F, Viros A, Milagre C, Trunzer K, Bollag G, Spleiss O, Reis-Filho JS, Kong X, Koya RC, Flaherty KT, Chapman PB, Kim MJ, Hayward R, Martin M, Yang H, Wang Q, Hilton H, Hang JS, Noe J, Lambros M, Geyer F, Dhomen N, Niculescu-Duvaz I, Zambon A, Niculescu-Duvaz D, Preece N, Robert L, Otte NJ, Mok S, Kee D, Ma Y, Zhang C, Habets G, Burton EA, Wong B, Nguyen H, Kockx M, Andries L, Lestini B, Nolop KB, Lee RJ, Joe AK, Troy JL, Gonzalez R, Hutson TE, Puzanov I, Chmielowski B, Springer CJ, McArthur GA, Sosman JA, Lo RS, Ribas A, Marais R. RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors. N Engl J Med. 2012 Jan 19;366(3):207-15.

Responsible Party:	Hoffmann-La Roche
ClinicalTrials.gov Identifier:	NCT01001299 History of Changes
Other Study ID Numbers:	NP22676
Study First Received:	October 21, 2009
Last Updated:	June 3, 2013
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on June 17, 2013