Invasive AspergillosisPhase 2NCT00404092
Caspofungin Maximum Tolerated Dose in Patients With Invasive Aspergillosis
A Phase 2 study testing caspofungin in people with Invasive Aspergillosis, run by University of Cologne at 4 sites in 2 countries.
Trial summary
This study investigates the safety and tolerability as well as the efficacy and pharmacokinetics of caspofungin in four escalating dosages in adult patients with hematologic malignancies and proven or probable invasive aspergillosis. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Invasive Aspergillosis
- What is being tested?
- caspofungin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 4 sitesin 2 countries
- Study dates
- Oct 2006to Oct 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Immunocompromised due to hematologic malignancies, bone marrow failure syndromes, hematopoietic stem cell transplantation, solid organ transplantation, other conditions resulting in severe neutropenia, HIV infection, prolonged corticosteroid therapy, treatment with other immunosuppressive medications, or other immunocompromising conditions that place patients at risk for invasive fungal infections.
- Evidence of proven or probable invasive aspergillosis, by modified EORTC criteria
Who cannot join
- Concomitant other systemic antifungal agents are not permitted on study.
- Chronic invasive fungal infection, defined as signs/symptoms of invasive fungal infection present for > 4 weeks preceding entry into study
- Prior systemic therapy of ≥ 4 days with any polyene anti-fungal agent within 14 days of study enrollment
- Prior systemic therapy of ≥ 4 days with non-polyenes for the current, documented IFI.
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
Germany3 sites
Charité - Campus Benjamin Franklin
Berlin, 12200
Klinikum der Universität zu Köln
Cologne, 50924
Universitätsklinikum Münster
Münster, 48149
About this study
Official title: A Phase II Dose Escalation Study of Caspofungin in Patients With Invasive Aspergillosis
This study investigates the safety and tolerability as well as the efficacy and pharmacokinetics of caspofungin in four escalating dosages in adult patients with hematologic malignancies and proven or probable invasive aspergillosis.
Read the detailed description
Due to its efficacy and a broad antifungal spectrum against relevant fungal pathogens, lack of cross-resistance to azoles and amphotericin B, documented efficacy against human Aspergillus infections, favorable pharmacokinetic properties, and excellent tolerability according to the current data, caspofungin is a highly promising candidate for improving the results of treatment of invasive fungal infections.
Preclinical and clinical data indicate a dose dependent antifungal efficacy of caspofungin as well as of other echinocandins such as micafungin and anidulafungin. Thus it appears reasonable to investigate the impact of higher doses of caspofungin to improve the results already achieved with this component so far.
The maximum tolerated dose (MTD) of caspofungin and the distribution of the drug in patients following administration of doses of 70 mg or more are not yet known. We therefore investigate the safety, tolerability and pharmacokinetics of caspofungin in rising doses in a dose escalation study in adult patients with proven or probable invasive aspergillosis.
- Conditions
- Invasive Aspergillosis
- Being tested
- caspofungin
- Keywords
- aspergillosis, caspofungin, maximum tolerated dose
- Medical subject headings
- Aspergillosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
caspofunginDrug
Also called cancidas
i.v.
| Study group | Role | What they receive |
|---|---|---|
| 1st cohort | Experimental | 70mg caspofungin 1x/day Receives: Drug: caspofungin |
| 2nd cohort | Experimental | 100mg caspofungin 1x/day Receives: Drug: caspofungin |
| 3rd cohort | Experimental | 150mg caspofungin 1x/day Receives: Drug: caspofungin |
| 4th cohort | Experimental | 200mg caspofungin 1x/day Receives: Drug: caspofungin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Tolerability of Caspofungin in Four Escalating Dosages in Adult Patients With Hematologic Malignancies and Proven or Probable Invasive Aspergillosis
Endpoints of safety and tolerability are the number of toxicity-related study therapy discontinuations and grade III and IV clinical and laboratory events, as evaluated on the basis of current NCI criteria.
Measured: End of caspofungin treatment, treatment duration varied between 3 and 29 days (mean: 20.5; median: 24.5)
Secondary outcomes (1)
Efficacy of Caspofungin in Four Escalating Dosages in the Treatment of Proven or Probable Invasive Aspergillosis.
Numbers of patients in each dose cohort according to invasive aspergillosis (IA) outcome at end of protocol treatment (EOT), 4 weeks follow-up (4w FU) and 12 weeks follow-up (12w FU), respectively. 12w FU was only required for patients with a CR or PR at the 4w FU.
Definitions:
CR: resolution of all attributable symptoms, signs, and radiographic or bronchoscopic abnormalities.
PR: clinically meaningful improvement in attributable symptoms, signs, and radiographic (min. 50% decrease) or bronchoscopic abnormalities.
Stable disease (SD): no improvement in attributable symptoms, signs, and radiographic or bronchoscopic abnormalities.
Failure: deterioration in attributable clinical or radiographic abnormalities necessitating alternative antifungal therapy or resulting in death.
Relapse: reemergence of IA after EOT following CR, PR or SD or early withdrawal.
Measured: End of caspofungin treatment; 4 weeks follow-up; 12 weeks follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Nov 2006 (estimated)
- Study startOct 2006
- Primary completionOct 2009
- Study completionOct 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Invasive AspergillosisStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cologne
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Oliver Cornely, MD, University of Cologne
- Investigators
- Oliver A. Cornely, MD, Principal investigator, Klinikum der Universität zu Köln
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00404092
- Sponsor's protocol ID
- Uni-Koeln-687
- Other IDs
- 2006-001936-30
- Status last verified
- Jul 2013
- First submitted
- 24 Nov 2006
- Last updated
- 31 Jul 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Cornely OA, Vehreschild JJ, Vehreschild MJ, Wurthwein G, Arenz D, Schwartz S, Heussel CP, Silling G, Mahne M, Franklin J, Harnischmacher U, Wilkens A, Farowski F, Karthaus M, Lehrnbecher T, Ullmann AJ, Hallek M, Groll AH. Phase II dose escalation study of caspofungin for invasive Aspergillosis. Antimicrob Agents Chemother. 2011 Dec;55(12):5798-803. doi: 10.1128/AAC.05134-11. Epub 2011 Sep 12.
PubMed 21911573Wurthwein G, Cornely OA, Trame MN, Vehreschild JJ, Vehreschild MJ, Farowski F, Muller C, Boos J, Hempel G, Hallek M, Groll AH. Population pharmacokinetics of escalating doses of caspofungin in a phase II study of patients with invasive aspergillosis. Antimicrob Agents Chemother. 2013 Apr;57(4):1664-71. doi: 10.1128/AAC.01912-12. Epub 2013 Jan 18.
PubMed 23335740
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Dose Escalation Study of Caspofungin in Patients With Invasive Aspergillosis
- ClinicalTrials.gov ID
- NCT00404092
- Acronym / sponsor ID
- Uni-Koeln-687
- Conditions
- Invasive Aspergillosis
- Keywords
- aspergillosis, caspofungin, maximum tolerated dose
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- University of CologneUniversity, hospital or other
- Study start
- Oct 2006
- Primary completion
- Oct 2009 (actual)
- Study completion
- Oct 2009 (actual)
- First posted
- 27 Nov 2006 (estimated)
- Results
- Posted 21 Jan 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study investigates the safety and tolerability as well as the efficacy and pharmacokinetics of caspofungin in four escalating dosages in adult patients with hematologic malignancies and proven or probable invasive aspergillosis.
Detailed description
Due to its efficacy and a broad antifungal spectrum against relevant fungal pathogens, lack of cross-resistance to azoles and amphotericin B, documented efficacy against human Aspergillus infections, favorable pharmacokinetic properties, and excellent tolerability according to the current data, caspofungin is a highly promising candidate for improving the results of treatment of invasive fungal infections.
Preclinical and clinical data indicate a dose dependent antifungal efficacy of caspofungin as well as of other echinocandins such as micafungin and anidulafungin. Thus it appears reasonable to investigate the impact of higher doses of caspofungin to improve the results already achieved with this component so far.
The maximum tolerated dose (MTD) of caspofungin and the distribution of the drug in patients following administration of doses of 70 mg or more are not yet known. We therefore investigate the safety, tolerability and pharmacokinetics of caspofungin in rising doses in a dose escalation study in adult patients with proven or probable invasive aspergillosis.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1st cohort | Experimental | Drug: caspofungin70mg caspofungin 1x/day |
| 2nd cohort | Experimental | Drug: caspofungin100mg caspofungin 1x/day |
| 3rd cohort | Experimental | Drug: caspofungin150mg caspofungin 1x/day |
| 4th cohort | Experimental | Drug: caspofungin200mg caspofungin 1x/day |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Immunocompromised due to hematologic malignancies, bone marrow failure syndromes, hematopoietic stem cell transplantation, solid organ transplantation, other conditions resulting in severe neutropenia, HIV infection, prolonged corticosteroid therapy, treatment with other immunosuppressive medications, or other immunocompromising conditions that place patients at risk for invasive fungal infections.
- Evidence of proven or probable invasive aspergillosis, by modified EORTC criteria
Key exclusion criteria (4 listed)
- Concomitant other systemic antifungal agents are not permitted on study.
- Chronic invasive fungal infection, defined as signs/symptoms of invasive fungal infection present for > 4 weeks preceding entry into study
- Prior systemic therapy of ≥ 4 days with any polyene anti-fungal agent within 14 days of study enrollment
- Prior systemic therapy of ≥ 4 days with non-polyenes for the current, documented IFI.
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 |
|---|---|---|
| caspofunginAlso: cancidasi.v. | Drug | 1st cohort, 2nd cohort, 3rd cohort, 4th cohort |
Primary outcome
Safety and Tolerability of Caspofungin in Four Escalating Dosages in Adult Patients With Hematologic Malignancies and Proven or Probable Invasive Aspergillosis
Time frame: End of caspofungin treatment, treatment duration varied between 3 and 29 days (mean: 20.5; median: 24.5)
Endpoints of safety and tolerability are the number of toxicity-related study therapy discontinuations and grade III and IV clinical and laboratory events, as evaluated on the basis of current NCI criteria.
1 secondary outcome
Efficacy of Caspofungin in Four Escalating Dosages in the Treatment of Proven or Probable Invasive Aspergillosis.
Time frame: End of caspofungin treatment; 4 weeks follow-up; 12 weeks follow-up
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 21911573Cornely OA, Vehreschild JJ, Vehreschild MJ, Wurthwein G, Arenz D, Schwartz S, Heussel CP, Silling G, Mahne M, Franklin J, Harnischmacher U, Wilkens A, Farowski F, Karthaus M, Lehrnbecher T, Ullmann AJ, Hallek M, Groll AH. Phase II dose escalation study of caspofungin for invasive Aspergillosis. Antimicrob Agents Chemother. 2011 Dec;55(12):5798-803. doi: 10.1128/AAC.05134-11. Epub 2011 Sep 12.
- Results publication: PubMed 23335740Wurthwein G, Cornely OA, Trame MN, Vehreschild JJ, Vehreschild MJ, Farowski F, Muller C, Boos J, Hempel G, Hallek M, Groll AH. Population pharmacokinetics of escalating doses of caspofungin in a phase II study of patients with invasive aspergillosis. Antimicrob Agents Chemother. 2013 Apr;57(4):1664-71. doi: 10.1128/AAC.01912-12. Epub 2013 Jan 18.
Related trials for Invasive Aspergillosis
RecruitingObservational study
Natural History of Individuals With Immune System Problems That Lead to Fungal Infections
Chronic Mucocutaneous Candidiasis, Invasive Aspergillosis
RecruitingObservational study
Fungal Status and Prognosis in ABPA
ABPA, Allergic Bronchopulmonary Aspergillosis
RecruitingObservational study
Derivation and Validation of the Fungal Pneumonia Assessment and Likelihood Predictor Score
Pneumonia, Fungal Pneumonia
RecruitingObservational study
A Cohort Study of the Efficacy and Safety of Biologics in Patients With ABPA
ABPA, Biologics
Active, not recruitingObservational study
Liver Cirrhosis Patients With Invasive Pulmonary Aspergillosis: in Depth Understanding Clinical Host Risk Factors
Liver Cirrhosis, Viral Pneumonia
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.
Oliver A. Cornely, MD principal investigator
Klinikum der Universität zu Köln
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing caspofungin in people with Invasive Aspergillosis, run by University of Cologne at 4 sites in 2 countries.
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 2 inclusion and 4 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: finished, as of the sponsor's last update on 31 Jul 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Germany, Belgium. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Jan 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Safety and Tolerability of Caspofungin in Four Escalating Dosages in Adult Patients With Hematologic Malignancies and Proven or Probable Invasive Aspergillosis (time frame: End of caspofungin treatment, treatment duration varied between 3 and 29 days (mean: 20.5; median: 24.5)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00404092, which also lists 2 linked publications.
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 31 Jul 2013.