Solid Tumor MalignanciesPhase 1NCT01290380
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
A Phase 1 study testing ASA404, DMXAA, DXAA in people with Solid Tumor Malignancies, run by Novartis Pharmaceuticals at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumor Malignancies
- What is being tested?
- ASA404, DMXAA, DXAA
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 2 sitesUnited States
- Study dates
- Feb 2010to Nov 2010
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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:
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- 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 (http://medicine.iupui.edu/flockhart/)
- Other protocol-defined inclusion/exclusion criteria may apply
Trial locations and contacts
2 sites in 1 country.
United States2 sites
The University of Texas Science Center at Houston
Houston, Texas, 77030
University of Wisconsin & Paul P. Carbone Comprehensive Cancer Center
Madison, Wisconsin, 53792
About this study
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
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.
- Conditions
- Solid Tumor Malignancies
- Being tested
- ASA404, DMXAA, DXAA
- Keywords
- Solid tumor malignancies,, simvastatin,, caffeine,, omeprazole and diclofenac,, ASA404,, PK data
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ASA404, DMXAA, DXAADrug
ASA404 (5,6-dimethylxantheone-4-acetic acid) DMXAA or DXAA
| Study group | Role | What they receive |
|---|---|---|
| ASA 404 + standard chemotherapy | Experimental | ASA 404 in combination with in combination with standard chemotherapy (paclitaxel + carboplatin or docetaxel) and a cocktail of caffeine, diclofenac, simvastatin and omeprazole Receives: Drug: ASA404, DMXAA, DXAA |
What is being measured
The primary outcome is the main question the study is designed to answer.
evaluate the effects of ASA404 on the pharmacokinetics of a cocktail of simvastatin, caffeine, omeprazole, and diclofenac in patients with advanced malignancies.
Measured: 12 months
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.
Measured: 12 months
Secondary outcomes (4)
Pharmacokinetic parameters of caffeine, diclofenca, simvastatin, and omeprazole, including AUC (0-tlast), AUC (0-inf), t½,CL/F, Vz/F, Cmax, and tmax.
Measured: 12 months
Pharmacokinetic parameters of ASA404 including AUC (0-tlast), Cmax, and Tmax
Measured: 4 Months
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.
Other safety data (e.g. vital signs, electrocardiograms, and ophthalmic assessments) will be considered as appropriate.
Measured: 4 months
assess the safety and tolerability of ASA404
Measured: 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2011 (estimated)
- Study startFeb 2010
- Primary completionNov 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid Tumor MalignanciesStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01290380
- Sponsor's protocol ID
- CASA404A2111
- Status last verified
- Aug 2011
- First submitted
- 26 Jan 2011
- Last updated
- 2 Sep 2011
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01290380
- Acronym / sponsor ID
- CASA404A2111
- Conditions
- Solid Tumor Malignancies
- Keywords
- Solid tumor malignancies,, simvastatin,, caffeine,, omeprazole and diclofenac,, ASA404,, PK data
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 54 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Feb 2010
- Primary completion
- Nov 2010 (actual)
- First posted
- 7 Feb 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ASA 404 + standard chemotherapy | Experimental | Drug: ASA404, DMXAA, DXAAASA 404 in combination with in combination with standard chemotherapy (paclitaxel + carboplatin or docetaxel) and a cocktail of caffeine, diclofenac, simvastatin and omeprazole |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ASA404, DMXAA, DXAAASA404 (5,6-dimethylxantheone-4-acetic acid) DMXAA or DXAA | Drug | ASA 404 + standard chemotherapy |
Primary outcome
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
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
4 secondary outcomes
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
Pharmacokinetic parameters of ASA404 including AUC (0-tlast), Cmax, and Tmax
Time frame: 4 Months
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
assess the safety and tolerability of ASA404
Time frame: 4 months
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2011.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ASA404, DMXAA, DXAA in people with Solid Tumor Malignancies, run by Novartis Pharmaceuticals at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 2 Sep 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2011.