Pancreatic NeoplasmsPhase 1NCT00844064
Safety and Tolerability of AP 12009, Administered I.V. in Patients With Advanced Tumors Known to Overproduce TGF-beta-2
A Phase 1 study testing AP 12009 in people with Pancreatic Neoplasms and Melanoma, run by Isarna Therapeutics GmbH at 10 sites in Germany.
Trial summary
In this national Phase I dose-escalation study the safety and tolerability of AP 12009 is evaluated in adult patients with advanced tumors known to overproduce TGF-β2, who are not or no longer amenable to established therapies. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Pancreatic Neoplasms, Melanoma, Colorectal Neoplasms
- What is being tested?
- AP 12009
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 62 participants
- Where
- 10 sitesGermany
- Study dates
- Jan 2005to Nov 2011
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent.
- Age: 18-75 years.
- Male or non-pregnant, non-lactating female.
- a.Pancreatic cancer: Histologically or cytologically confirmed diagnosis, stage IVA or IVB (AJCC, 1997).
- Melanoma: Histologically or cytologically confirmed diagnosis, stage III or IV (AJCC, UICC).
- Colorectal cancer: Histologically or cytologically confirmed diagnosis, stage III or IV (AJCC, UICC), excluded from the last cohort.
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- Patient is not or no longer amenable to established forms of therapy.
- At least one measurable lesion.
- Karnofsky performance status of at least 80%.
- Recovery from acute toxicity caused by any previous therapy.
- Adequate organ function as assessed by the following laboratory values:
- Serum creatinine and urea < 2 times the upper limit of normal (ULN).
- ALT and AST < 3 ULN (in case of a liver metastasis: < 5x ULN); alkaline phosphatase < 3 ULN; and bilirubin < 2.5 mg/dL.
- Prothrombin time < 1.5 INR and PTT < 1.5 times the upper limit of normal.
- Hemoglobin > 9 g/dL.
- Platelets > 100 x 10E9/L.
- WBC > 3.0 x 10E9/L.
- Absolute Neutrophil Count (ANC) > 1.5 x 10E9/L.
Who cannot join
- Patient unable to comply with the protocol regulations.
- Pregnant or lactating female.
- Antitumor radiation therapy within 12 weeks, tumor surgery within 4 weeks or any other therapy with established antitumor effects within 2 weeks prior to study entry.
- The patient takes or is likely to need other prohibited concomitant medication. Administration of corticosteroids should be strictly avoided during the course of the study.
- Patient's participation in another clinical trial with investigational medication within 30 days prior to study entry.
- History of brain metastases. In the case of suspected brain metastases a CT scan of the skull will be performed (not mandatory in asymptomatic patients).
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- Clinically significant cardiovascular abnormalities such as refractory hypertension, congestive heart failure, unstable angina, or poorly controlled arrhythmia, or a myocardial infarction within 6 months prior to treatment.
- Gastric or duodenal ulcers within 6 months before study entry or is at risk of gastrointestinal ulceration due to high consumption of NSAIDs.
- An active infection with HIV, HBV, or HCV.
- Clinically significant acute viral, bacterial, or fungal infection.
- Acute medical problems that may be considered to become an unacceptable risk, or any conditions that might be contraindications for starting study treatment.
- History of allergies to reagents used in this study.
- Drug abuse or extensive use of alcohol.
- Significant psychiatric disorders/ legal incapacity or limited legal capacity.
- History of Long QT Syndrome or QTc time ≥ 480 msec in screening/baseline ECGs. The average QTc time is to be calculated from three separate ECGs performed prior to start of infusion: two ECGs performed at Screening/Baseline (with a minimum 1-hour interval in between) and one performed within 1 hour prior to start of infusion.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
Germany10 sites
Universitätsmedizin Berlin Charité
Berlin, 10117
Universitätsklinik und Poliklinik für Innere Medizin I
Halle, 06120
Hautklinik der Ruprecht-Karls-Universität Heidelberg
Heidelberg, 69115
Universitätsklinikum Schleswig-Holstein
Kiel, 24105
Krankenhaus rechts der Isar, II. Medizinische Klinik und Poliklinik
München, 81675
Universität Münster, Klinik und Poliklinik für Hautkrankheiten
Münster, 48149
Klinik und Poliklinik für Innere Medizin I
Regensburg, 93042
Klinik und Poliklinik für Dermatologie
Regensburg, 93053
Universitäts-Hautklinik, Sektion Dermatologische Onkologie
Tübingen, 72076
Universitätsklinikum Ulm, Zentrum für Innere Medizin
Ulm, 89081
About this study
Official title: An Open-Label, Multicenter Dose-Escalation Study to Evaluate the Safety and Tolerability of AP 12009 (Trabedersen), Administered Intravenously in Patients With Advanced Tumors Known to Overproduce TGF-β2.
In this national Phase I dose-escalation study the safety and tolerability of AP 12009 is evaluated in adult patients with advanced tumors known to overproduce TGF-β2, who are not or no longer amenable to established therapies.
Read the detailed description
The purpose of this dose-finding study is to evaluate the safety and tolerability of AP 12009. Two fixed dose-escalation schemes with predefined steps and increasing increments have been selected to determine the maximum tolerated dose (MTD) as well as the dose-limiting toxicity (DLT). At least two cycles of AP 12009 are administered intravenously in adult patients with no further acknowledged treatment options.
AP 12009 (trabedersen) is a phosphorothioate antisense oligodeoxynucleotide specific for the mRNA of human Transforming Growth Factor beta 2 (TGF-beta-2). The growth factor TGF-beta plays a key role in malignant progression of various tumors by inducing proliferation, invasion, metastasis, angiogenesis, and escape from immunosurveillance. In patients with pancreatic cancer, colorectal cancer, and metastatic melanoma the TGF-beta-2 overexpression is associated with disease stage, clinical prognosis, and the immunodeficient state of the patients.
- Conditions
- Pancreatic Neoplasms, Melanoma, Colorectal Neoplasms
- Being tested
- AP 12009
- Keywords
- Pancreatic cancer, Metastatic melanoma, Advanced tumor, Targeted therapy, Antisense, Transforming Growth Factor beta 2, Dose escalation
- Medical subject headings
- Pancreatic Neoplasms, Melanoma, Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AP 12009Drug
Initial scheme: AP 12009 (trabedersen), dose escalation scheme, continuous intravenous infusion (7 days), every other week, up to 10 cycles.
Modified scheme: AP 12009 (trabedersen), dose escalation scheme, continuous intravenous infusion (4 days), every other week, up to 10 cycles
| Study group | Role | What they receive |
|---|---|---|
| AP 12009 | Experimental | Not described Receives: Drug: AP 12009 |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the maximum tolerated dose (MTD) as well as the dose-limiting toxicity (DLT) of two cycles of AP 12009 administered intravenously at weekly intervals and for four days every other week.
Secondary outcomes (5)
To determine the safety and tolerability of AP 12009 administered intravenously at weekly intervals and for four days every other week.
To assess the plasma pharmacokinetic profile of AP 12009 administered intravenously at weekly intervals and for four days every other week.
To establish a suitable determination method and to assess the urine pharmacokinetic profile of AP 12009 administered intravenously for four days every other week.
To determine the effect of AP 12009 administered intravenously at weekly intervals and for four days every other week on TGF-β2 plasma concentration levels.
To determine the potential antitumor activity of AP 12009 administered intravenously at weekly intervals and for four days every other week, as assessed by the effect on tumor size and tumor markers.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2009 (estimated)
- Study startJan 2005
- Primary completionNov 2011
- Study completionNov 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pancreatic NeoplasmsStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- Isarna Therapeutics GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Helmut Oettle, MD, Study chair, Charité Berlin Campus Virchow-Klinikum
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00844064
- Sponsor's protocol ID
- AP 12009-P001
- Status last verified
- Feb 2019
- First submitted
- 12 Feb 2009
- Last updated
- 15 Feb 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Multicenter Dose-Escalation Study to Evaluate the Safety and Tolerability of AP 12009 (Trabedersen), Administered Intravenously in Patients With Advanced Tumors Known to Overproduce TGF-β2.
- ClinicalTrials.gov ID
- NCT00844064
- Acronym / sponsor ID
- AP 12009-P001
- Conditions
- Pancreatic Neoplasms, Melanoma, Colorectal Neoplasms
- Keywords
- Pancreatic cancer, Metastatic melanoma, Advanced tumor, Targeted therapy, Antisense, Transforming Growth Factor beta 2, Dose escalation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- Isarna Therapeutics GmbHIndustry (pharma, biotech, devices)
- Study start
- Jan 2005
- Primary completion
- Nov 2011 (actual)
- Study completion
- Nov 2011 (actual)
- First posted
- 13 Feb 2009 (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.
In this national Phase I dose-escalation study the safety and tolerability of AP 12009 is evaluated in adult patients with advanced tumors known to overproduce TGF-β2, who are not or no longer amenable to established therapies.
Detailed description
The purpose of this dose-finding study is to evaluate the safety and tolerability of AP 12009. Two fixed dose-escalation schemes with predefined steps and increasing increments have been selected to determine the maximum tolerated dose (MTD) as well as the dose-limiting toxicity (DLT). At least two cycles of AP 12009 are administered intravenously in adult patients with no further acknowledged treatment options.
AP 12009 (trabedersen) is a phosphorothioate antisense oligodeoxynucleotide specific for the mRNA of human Transforming Growth Factor beta 2 (TGF-beta-2). The growth factor TGF-beta plays a key role in malignant progression of various tumors by inducing proliferation, invasion, metastasis, angiogenesis, and escape from immunosurveillance. In patients with pancreatic cancer, colorectal cancer, and metastatic melanoma the TGF-beta-2 overexpression is associated with disease stage, clinical prognosis, and the immunodeficient state of the patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AP 12009 | Experimental | Drug: AP 12009 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Written informed consent.
- Age: 18-75 years.
- Male or non-pregnant, non-lactating female.
- a.Pancreatic cancer: Histologically or cytologically confirmed diagnosis, stage IVA or IVB (AJCC, 1997).
- Patient is not or no longer amenable to established forms of therapy.
Key exclusion criteria (15 listed)
- Patient unable to comply with the protocol regulations.
- Pregnant or lactating female.
- Antitumor radiation therapy within 12 weeks, tumor surgery within 4 weeks or any other therapy with established antitumor effects within 2 weeks prior to study entry.
- The patient takes or is likely to need other prohibited concomitant medication. Administration of corticosteroids should be strictly avoided during the course of the study.
- Patient's participation in another clinical trial with investigational medication within 30 days prior to study entry.
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 |
|---|---|---|
| AP 12009Initial scheme: AP 12009 (trabedersen), dose escalation scheme, continuous intravenous infusion (7 days), every other week, up to 10 cycles. Modified scheme: AP 12009 (trabedersen), dose escalation scheme, continuous intravenous infusion (4 days), every other week, up to 10 cycles | Drug | AP 12009 |
Primary outcome
To determine the maximum tolerated dose (MTD) as well as the dose-limiting toxicity (DLT) of two cycles of AP 12009 administered intravenously at weekly intervals and for four days every other week.
5 secondary outcomes
To determine the safety and tolerability of AP 12009 administered intravenously at weekly intervals and for four days every other week.
To assess the plasma pharmacokinetic profile of AP 12009 administered intravenously at weekly intervals and for four days every other week.
To establish a suitable determination method and to assess the urine pharmacokinetic profile of AP 12009 administered intravenously for four days every other week.
To determine the effect of AP 12009 administered intravenously at weekly intervals and for four days every other week on TGF-β2 plasma concentration levels.
To determine the potential antitumor activity of AP 12009 administered intravenously at weekly intervals and for four days every other week, as assessed by the effect on tumor size and tumor markers.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2019.
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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.
Helmut Oettle, MD study chair
Charité Berlin Campus Virchow-Klinikum
10 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 AP 12009 in people with Pancreatic Neoplasms and Melanoma, run by Isarna Therapeutics GmbH at 10 sites in Germany.
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 18 inclusion and 15 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 15 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Germany. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To determine the maximum tolerated dose (MTD) as well as the dose-limiting toxicity (DLT) of two cycles of AP 12009 administered intravenously at weekly intervals and for four days every other week.. 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 15 Feb 2019.