A Study to Evaluate the Effects of ASA404 Alone or in Combination With Taxane-based Chemotherapies on the Pharmacokinetics of Drugs in Patients With Advanced Solid Tumor Malignancies

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: NCT01290380
Recruitment Status : Terminated
First Posted : February 7, 2011
Last Update Posted : September 2, 2011
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
The purpose of this study is to evaluate the potential inhibitory effects of ASA404 on CYP1A2, CYP2C9, CYP3A4 and CYP2C19 mediated metabolism on the respective probe drugs caffeine, diclofenac, simvastatin, and omeprazole, respectively. This will be accomplished by the simultaneous administration of four substrates as part of a cocktail in order to characterize the potential for in-vivo drug-drug interactions. This cocktail approach has been proposed per FDA guidance as a screening tool for potential in-vivo drug-drug interactions Compared to the individual administration of specific probes in multiple studies, simultaneous administration of multiple in-vivo probes of drug-metabolizing enzymes offer several distinct advantages such as minimizing the confounding influence of inter-individual and intra-individual variability over time. Substrates for the CYP enzymes were chosen based on the FDA guidance recommendations taking into account that 1. The substrates are specific for the individual CYP enzymes, 2. There are no interactions among these substrates; and 3. The study will be conducted in a sufficient number of subjects.

Condition or disease Intervention/treatment Phase
Solid Tumor Malignancies Drug: ASA404, DMXAA, DXAA Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 54 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, Multi-center Study to Evaluate the Effects of ASA404 Alone and in Combination With Taxane-based Chemotherapy on the Pharmacokinetics of Simvastatin, Caffeine, Omeprazole, and Diclofenac in Patients With Advanced Solid Tumor Malignancies
Study Start Date : February 2010
Actual Primary Completion Date : November 2010

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Caffeine

Arm Intervention/treatment
Experimental: ASA 404 + standard chemotherapy
ASA 404 in combination with in combination with standard chemotherapy (paclitaxel + carboplatin or docetaxel) and a cocktail of caffeine, diclofenac, simvastatin and omeprazole
ASA404 (5,6-dimethylxantheone-4-acetic acid) DMXAA or DXAA

Primary Outcome Measures :
  1. evaluate the effects of ASA404 on the pharmacokinetics of a cocktail of simvastatin, caffeine, omeprazole, and diclofenac in patients with advanced malignancies. [ Time Frame: 12 months ]
  2. evaluate the effects of ASA404 combined with either paclitaxel + carboplatin or docetaxel on the pharmacokinetics of a cocktail of simvastatin, caffeine, omeprazole, and diclofenac in patients with advanced malignancies. [ Time Frame: 12 months ]

Secondary Outcome Measures :
  1. Pharmacokinetic parameters of caffeine, diclofenca, simvastatin, and omeprazole, including AUC (0-tlast), AUC (0-inf), t½,CL/F, Vz/F, Cmax, and tmax. [ Time Frame: 12 months ]
  2. Pharmacokinetic parameters of ASA404 including AUC (0-tlast), Cmax, and Tmax [ Time Frame: 4 Months ]
  3. assessment of safety based mainly on the frequency and severity of adverse events and the number of laboratory values worsening from baseline based on the CTCAE grade. [ Time Frame: 4 months ]
    Other safety data (e.g. vital signs, electrocardiograms, and ophthalmic assessments) will be considered as appropriate.

  4. assess the safety and tolerability of ASA404 [ Time Frame: 4 months ]

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

Inclusion Criteria:

Histologically-proven and radiologically-confirmed diagnosis of advanced or metastatic solid tumors for whom treatment with an investigational agent alone or in combination with docetaxel or placlitaxel +carboplatin is appropriate;

  • Body Mass Index (BMI) must be within the range of 18-30;
  • A minimum of 4 weeks must have elapsed since the last treatment with other cancer therapies, (i.e. endocrine therapy, immunotherapy, chemotherapy, ect);
  • Willing and able to remain in the clinic for at least 2 days (the night before dosing and the night after dosing 24 hours) for the 3 x's receiving the cocktail (on Day 1, Day 8 and Day 15 during the

Exclusion Criteria:

  • Patients having CNS metastases. (Patients having any clinical signs of CNS metastases must have a CT or MRI of the brain performed to rule out CNS metastases in order to be eligible for the study participation. Patients who have had brain metastases surgically removed or irradiated with no active residual disease confirmed by imaging are allowed)
  • Patients who have not recovered from all acute radiotherapy-related toxicities;
  • Prior exposure to Vascular Disrupting Agents (VDAs) or other vascular targeting agents
  • Right bundle branch block (RBBB), complete left bundle branch block (LBBB), bifascicular block (right bundle branch block with either left anterior hemiblock or left posterior hemiblock)
  • Concomitant use of drugs with a risk of QT prolongation and/or causing torsade de pointes

If patient will be treated with paclitaxel:

  • Known allergy or hypersensitivity to platinum-containing drugs, taxanes, other drugs formulated in Cremophor EL (polyoxyethylated castor oil) or any known excipients of these drugs
  • Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions while taking paclitaxel and therefore are not considered effective contraceptive methods for this study when used as a single agent. Patients taking oral, implantable, or injectable contraceptives who are not willing or otherwise unable to use a concomitant barrier method will be excluded. The Investigator shall counsel the patient accordingly. For a list of substrates of human liver microsomal P450 enzymes, visit website (

Other protocol-defined inclusion/exclusion criteria may apply

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): NCT01290380

United States, Texas
The University of Texas Science Center at Houston
Houston, Texas, United States, 77030
United States, Wisconsin
University of Wisconsin & Paul P. Carbone Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
Novartis Pharmaceuticals
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

Responsible Party: Novartis Pharmaceuticals Identifier: NCT01290380     History of Changes
Other Study ID Numbers: CASA404A2111
First Posted: February 7, 2011    Key Record Dates
Last Update Posted: September 2, 2011
Last Verified: August 2011

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Solid tumor malignancies,
omeprazole and diclofenac,
PK data

Additional relevant MeSH terms:
Anticholesteremic Agents
Hypolipidemic Agents
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors
Central Nervous System Stimulants
Physiological Effects of Drugs
Phosphodiesterase Inhibitors
Purinergic P1 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Anti-Ulcer Agents
Gastrointestinal Agents
Proton Pump Inhibitors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Anti-Inflammatory Agents