Trial record 1 of 1 for:    NCT01901172
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A Study of the Drug-Drug Interaction of RO5503781 and Posaconazole and of the Relative Bioavailability of New Formulations of RO5503781 in Patients With Solid Tumors

This study is currently recruiting participants.
Verified April 2014 by Hoffmann-La Roche
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01901172
First received: July 9, 2013
Last updated: April 7, 2014
Last verified: April 2014
  Purpose

This multicenter, open-label study will evaluate the effect of posaconazole on the pharmacokinetics of RO5503781 and the relative bioavailability of two new RO5503781 formulations in patients with solid tumors.


Condition Intervention Phase
Neoplasms
Drug: RO5503781
Drug: posaconazole
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: A MULTIPLE-CENTER, OPEN-LABEL CLINICAL PHARMACOLOGY STUDY WITH RO5503781, AN MDM2 ANTAGONIST, IN PATIENTS WITH SOLID TUMORS TO DETERMINE: PART 1 ONE-SEQUENCE, 2-PERIOD CROSSOVER DESIGN TO INVESTIGATE THE EFFECT OF POSACONAZOLE, A STRONG CYP3A4 INHIBITOR, ON THE PHARMACOKINETICS AND PHARMACODYNAMICS OF RO5503781 PART 2 A RANDOMIZED, SINGLE DOSE, 3 PERIOD CROSSOVER DESIGN TO INVESTIGATE THE RELATIVE BIOAVAILABILITY OF TWO NEW RO5503781 TABLET FORMULATIONS FOLLOWING ORAL ADMINISTRATION

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Part 1: Area under the concentration-time curve (AUC) [ Time Frame: 22 days ] [ Designated as safety issue: No ]
  • Part 1: Maximum concentration (Cmax) [ Time Frame: 22 days ] [ Designated as safety issue: No ]
  • Part 1: Change in serum macrophage inhibitory cytokine-1 (MIC-1) [ Time Frame: from baseline to Day 22 ] [ Designated as safety issue: No ]
  • Part 2: Relative bioavailability: Area under the concentration-time curves (AUCs) [ Time Frame: 22 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety: Incidence of adverse events in combination with posaconazole [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • Safety: Incidence of adverse events (new formulations) [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • Safety: Incidence of adverse events (optional treatment extension) [ Time Frame: approximately 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: August 2013
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1: Drug-drug interaction Drug: RO5503781
Single doses Days 1 and 11
Drug: posaconazole
Multiple doses Days 8-14
Experimental: Part 2: Relative bioavailability Drug: RO5503781
Single doses of current formulation, optimized MBP formulation and new SDP formulation, Days 1, 8 and 15 in a crossover design
Experimental: Extension Drug: RO5503781
Daily for 5 days followed by 23 days rest per cycle

  Eligibility

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

Inclusion Criteria:

  • Adult patients, >/= 18 years of age
  • Histologically or cytologically confirmed advanced malignancies, except all forms of leukemia and lymphoma, for which standard curative or palliative measures do not exist, are no longer effective, or are not acceptable to the patient
  • Measureable or evaluable disease (by RECIST criteria version 1.1 for solid tumors prior to the administration of study drug
  • Life expectancy of >/= 12 weeks.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
  • Female patients of childbearing potential and male patients who are not surgically sterile must be willing to use effective methods of contraception as defined by protocol during the treatment period and for 10 days after the last dose of RO5503781.
  • There are no limitations on additional, allowable type and amount of prior anti-tumor therapy. Acute toxicities from any prior anti-tumor therapy, surgery, or radiotherapy must have resolved to NCI-CTCAE version 4.03 Grade </= 1. The last dose of prior therapy must >/= 21 days prior to the first administration of study drug RO5503781 (or >/= 5 x terminal half-life of that therapy).
  • Adequate bone marrow, hepatic and renal function
  • Patients with stable CNS metastases (have had therapy or do not require therapy, are off steroids, have no change on screening CT or MRI and are asymptomatic), are eligible

Exclusion Criteria:

  • Any form of leukemia except for Stage 0 and 1 chronic lymphocytic leukemia (CLL) not requiring treatment in addition to the underlying malignancy
  • Hormonal therapy within the 2 weeks prior to the first dose of study medication. Patients with prostate cancer who are not surgically castrated should remain on GnRH analogues.
  • Patients who are using other investigational agents or who received investigational drugs </= 4 weeks prior to study treatment start.
  • Pre-existing GI disorders that may interfere with proper absorption of the drug(s), as per investigator discretion.
  • History of allergic reactions attributed to components of the formulated product
  • History of seizure disorders or unstable CNS metastases
  • Any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study
  • Patients who must receive CYP2C8 inhibitors, substrates or inducers, strong CYP 3A4 inducers or moderate/strong CYP3A4 inhibitors listed in protocol while on study. Substrates, inducers, and inhibitors listed in protocol must be discontinued 7 or 14 days prior to start of study medication.
  • Evidence of electrolyte imbalance (treatment for correction of electrolyte imbalances is permitted during screening to meet eligibility)
  • Pregnant or breast feeding women
  • HIV-positive patients who are currently receiving combination anti-retroviral therapy
  • Patients with known coagulopathy, platelet disorder or history of non-drug induced thrombocytopenia.
  • Patients receiving oral or parenteral anticoagulants/antiplatelet agents (e.g., chronic daily treatment with aspirin (> 325 mg/day), clopidogrel, low molecular weight heparin, or subcutaneous anticoagulant prophylaxis). A washout period of at least 7 days prior to the start of study is required. Patients may receive anticoagulant flushes for maintenance of indwelling catheters.
  • Patients who refuse to potentially receive blood products and/or have a hypersensitivity to blood products.
  • Part 1 only: Hypersensitivity to posaconazole, or any of the other ingredients, or any other azole antifungal
  • Part 1 only: Patients who cannot tolerate high-fat and/or full meals.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01901172

Contacts
Contact: Reference Study ID Number: NP28902 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. Only) global.rochegenentechtrials@roche.com

Locations
United States, Arizona
Completed
Scottsdale, Arizona, United States, 85258
United States, Texas
Recruiting
Dallas, Texas, United States, 75230
Canada, Ontario
Recruiting
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Recruiting
Montreal, Quebec, Canada, H3T 1E2
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01901172     History of Changes
Other Study ID Numbers: NP28902
Study First Received: July 9, 2013
Last Updated: April 7, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Posaconazole
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Trypanocidal Agents
Antiprotozoal Agents
Antiparasitic Agents

ClinicalTrials.gov processed this record on April 17, 2014