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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01901172
Recruitment Status : Completed
First Posted : July 17, 2013
Last Update Posted : August 18, 2015
Information provided by (Responsible Party):
Hoffmann-La Roche

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

Condition or disease Intervention/treatment Phase
Neoplasms Drug: RO5503781 Drug: posaconazole Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 61 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Study Start Date : August 2013
Actual Primary Completion Date : June 2015
Actual Study Completion Date : June 2015

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Extension Drug: RO5503781
Daily for 5 days followed by 23 days rest per cycle
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: Part 3: Food effect Drug: RO5503781
Single dose on Day 1 (high fat, low fat, or fasted), Day 10 (fasted, low fat, or high fat), and Day 19 (low fat, fasted, or high fat) in a crossover design

Primary Outcome Measures :
  1. Part 1: Area under the concentration-time curve (AUC) [ Time Frame: 22 days ]
  2. Part 1: Maximum concentration (Cmax) [ Time Frame: 22 days ]
  3. Part 1: Change in serum macrophage inhibitory cytokine-1 (MIC-1) [ Time Frame: from baseline to Day 22 ]
  4. Part 2: Relative bioavailability: Area under the concentration-time curves (AUCs) [ Time Frame: 22 days ]
  5. Part 3: Food effect: Area under the concentration-time curves (AUCs) [ Time Frame: 28 days ]

Secondary Outcome Measures :
  1. Safety: Incidence of adverse events in combination with posaconazole [ Time Frame: 28 days ]
  2. Safety: Incidence of adverse events (new formulations) [ Time Frame: 28 days ]
  3. Safety: Incidence of adverse events (optional treatment extension) [ Time Frame: approximately 1 year ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 and Part 3: Patients who cannot tolerate high-fat and/or full meals.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01901172

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

Responsible Party: Hoffmann-La Roche Identifier: NCT01901172     History of Changes
Other Study ID Numbers: NP28902
First Posted: July 17, 2013    Key Record Dates
Last Update Posted: August 18, 2015
Last Verified: August 2015

Additional relevant MeSH terms:
Antifungal Agents
Anti-Infective Agents
Trypanocidal Agents
Antiprotozoal Agents
Antiparasitic Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs