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Carcinoma, Pancreatic DuctalPhase 1/2Atu027-I-02NCT01808638

Atu027 Plus Gemcitabine in Advanced or Metastatic Pancreatic Cancer (Atu027-I-02)

A Phase 1/2 study testing Atu027 & gemcitabine in lead in safety period, Atu027 & gemcitabine in treatment arm 1 and Atu027 & gemcitabine in treatment arm 2 in people with Carcinoma, Pancreatic Ductal, run by Silence Therapeutics GmbH at 9 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of the study is to evaluate a new treatment strategy for advanced pancreatic cancer disease by combining the new investigational medicinal product Atu027 with the standard chemotherapeutic gemcitabine. This combination aims at enhancing gemcitabine´s anti-tumor activity with Atu027. Read more about this study

Who is it for?
Ages 18 to 84 years
Conditions the study is for
Carcinoma, Pancreatic Ductal
What is being tested?
Atu027 & gemcitabine in lead in safety period, Atu027 & gemcitabine in treatment arm 1 and Atu027 & gemcitabine in treatment arm 2
Could I receive a placebo?
No, everyone receives an active treatment
How many people
29 participants
Where
9 sitesGermany
Study dates
Mar 2013to Jan 2016
Phase
Phase 1/2
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 84 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Lead-in safety period:
  • Subjects between the age of 18 and 84 years
  • Histologically or cytologically confirmed advanced or refractory cholangiocellular carcinoma, biliary tract cancer, non-small-cell lung carcinoma, duodenal cancer, soft tissue sarcoma, ovarian carcinoma, or another non-pancreatic cancer disease indicated for gemcitabine treatment as determined by the investigator
  • Subjects who have previously received chemotherapy and standard curative or palliative care is not available, not effective, or unlikely to be effective
  • No option for surgical resection or radiation in curative intent
  • Eastern Cooperative Oncology Group (ECOG) performance status assessment of 0 to 2
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  • Life expectancy of at least 3 months
  • No interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung
  • Alanine aminotransferase (ALT) ≤3.0 x upper limit of normal (ULN; ≤5 x ULN for subjects with liver metastases)
  • Aspartate aminotransferase (AST) ≤3.0 x ULN (≤5 x ULN for subjects with liver involvement with cancer)
  • Total bilirubin ≤2.0 x ULN (liver metastasis <5 x ULN)
  • Serum creatinine ≤1.5 x ULN
  • Adequate bone marrow function: subjects should have an absolute granulocyte count of at least 1,500 (x 10e6/L) and platelet count of 100,000 (x 10e6/L) prior to the initiation of a cycle.
  • Prothrombin time-international normalized ratio/partial thromboplastin time (PT-INR/PTT) <1.5 x ULN (subjects who are being therapeutically anti-coagulated with an agent such as coumadin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists). Low-dose aspirin is permitted (≤100 mg daily).
  • Women of childbearing potential must have a negative urine pregnancy test at baseline.
  • Women of childbearing potential and men must be willing to use highly effective contraceptive methods during the course of the study and 6 months after.
  • Subjects must be willing and able (in the opinion of the investigator) to understand the subject information and informed consent form and to comply with the study protocol and procedures.
  • Subjects must be willing and able to give written informed consent.
  • Main part:
  • Subjects between the age of 18 and 84 years
  • Subjects with locally advanced or metastatic pancreatic adenocarcinoma stage III/IV indicated for gemcitabine treatment as determined by the investigator
  • No option for surgical resection or radiation in curative intent
  • Histological or cytological documentation of non-hematologic, malignant solid tumor
  • At least one measurable lesion or evaluable disease, as per the Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1
  • Eastern Cooperative Oncology Group (ECOG) performance status assessment of 0 to 2
  • Life expectancy of at least 3 months
  • No interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung
  • Alanine aminotransferase (ALT) <=3.0 x upper limit of normal (ULN; <=5 x ULN for subjects with liver metastases)
  • Aspartate aminotransferase (AST) <=3.0 x ULN (<=5 x ULN for subjects with liver involvement with cancer)
  • Total bilirubin <=2.0 x ULN (liver metastasis <=5 x ULN)
  • Serum creatinine <=1.5 x ULN
  • Adequate bone marrow function: subjects should have an absolute granulocyte count of at least 1,500 (x 10e6/L) and platelet count of 100,000 (x 10e6/L) prior to the initiation of a cycle.
  • Prothrombin time-international normalized ratio/partial thromboplastin time (PT INR/PTT) <1.5 x ULN (subjects who are being therapeutically anti-coagulated with an agent such as coumadin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists). Low-dose aspirin is permitted (≤100 mg daily).
  • Women of childbearing potential must have a negative urine pregnancy test at baseline.
  • Women of childbearing potential and men must be willing to use highly effective contraceptive methods during the course of the study and 6 months after.
  • Subjects must be willing and able (in the opinion of the investigator) to understand the subject information and informed consent form and to comply with the study protocol and procedures.
  • Subjects must be willing and able to give written informed consent.

Who cannot join

  • Lead-in safety period:
  • History of cardiac disease; congestive heart failure >New York Heart Association (NYHA) functional classification system Class II; active coronary artery disease, myocardial infarction within 6 months prior to study entry; new onset angina within 3 months prior to study entry or unstable angina, or ventricular cardiac arrhythmias requiring anti-arrhythmic therapy
  • Poorly controlled diabetes defined as hemoglobin A1c (HbA1c) >=7%
  • Poorly controlled hypertension, defined as systolic blood pressure >150 mmHg or diastolic pressure >90 mmHg, despite optimal medical management
  • Poorly controlled seizure disorder
  • Subjects undergoing renal dialysis
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  • Known hypersensitivity to the study drugs or active substances or excipients of the preparations
  • Pregnant or breast feeding
  • Known hepatitis B or C or human immunodeficiency virus (HIV) infection (if documented in the subject's record
  • Previous participation in this study
  • Current or previous (within 30 days of enrolment) treatment with another investigational drug or participation in another clinical study.
  • Subject is a relative of, or staff directly reporting to the investigator.
  • Subject is an employee of the sponsor.
  • Subject is committed under official or judicial order.
  • Any other reason that the investigator considers makes the subject unsuitable to participate
  • Main part:
  • History of cardiac disease; congestive heart failure >New York Heart Association (NYHA) functional classification system Class II; active coronary artery disease, myocardial infarction within 6 months prior to study entry; new onset angina within 3 months prior to study entry or unstable angina, or ventricular cardiac arrhythmias requiring anti-arrhythmic therapy
  • Poorly controlled diabetes defined as hemoglobin A1c (HbA1c) >=8%
  • Poorly controlled hypertension, defined as systolic blood pressure >150 mmHg or diastolic pressure >90 mmHg, despite optimal medical management
  • Poorly controlled seizure disorder
  • Subjects undergoing renal dialysis
  • Anticancer chemotherapy or immunotherapy during the study or before first study treatment. Subjects with recurrent disease after adjuvant treatment not progression-free for at least 6 months.
  • Radiotherapy to target lesions during study or before study start
  • Known hypersensitivity to the study drugs or active substances or excipients of the preparations
  • Pregnant or breast feeding
  • Known hepatitis B or C or human immunodeficiency virus (HIV) infection (if documented in the subject's record
  • Previous participation in this study
  • Current or previous (within 30 days of enrolment) treatment with another investigational drug or participation in another clinical study.
  • Subject is a relative of, or staff directly reporting to the investigator.
  • Subject is an employee of the sponsor.
  • Subject is committed under official or judicial order.
  • Any other reason that the investigator considers makes the subject unsuitable to participate

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

Germany9 sites

  • Charité - Universitätsmedizin Berlin Charité Centrum für Tumormedizin

    Berlin, 13353

  • Klinikum Dortmund gGmbH Medizinische Klinik Mitte

    Dortmund, 44137

  • Universitätsklinikum Freiburg, Innere Medizin II

    Freiburg im Breisgau, 79106

  • Medizinische Klinik III - Hämatologie/Onkologie Marienhospital Herne

    Herne, 44625

  • Klinikum Kassel GmbH Medizinischen Klinik IV;Onkologie,

    Kassel, 34125

  • Klinikum Nürnberg Nord Medizinische Klinik 5

    Nuremberg, 90419

  • Klinik und Poliklinik für Innere Medizin I Universitätsklinikum Regensburg

    Regensburg, 93042

  • Klinikum Stuttgart Klinik Hämatologie, Onkologie und Palliativmedizin

    Stuttgart, 70174

  • Universitätsklinikum Ulm Zentrum für Innere Medizin

    Ulm, 89061

Other trials in Germany

About this study

Official title: A PHASE Ib/IIa STUDY OF COMBINATION THERAPY WITH GEMCITABINE AND ATU027 IN SUBJECTS WITH LOCALLY ADVANCED OR METASTATIC PANCREATIC ADENOCARCINOMA

The purpose of the study is to evaluate a new treatment strategy for advanced pancreatic cancer disease by combining the new investigational medicinal product Atu027 with the standard chemotherapeutic gemcitabine. This combination aims at enhancing gemcitabine´s anti-tumor activity with Atu027.

The objectives of this clinical trial are to evaluate safety and activity of two Atu027 schedules in combination with standard gemcitabine treatment in patients with advanced or metastatic pancreatic adenocarcinoma.

Being tested
Atu027 & gemcitabine in lead in safety period, Atu027 & gemcitabine in treatment arm 1, Atu027 & gemcitabine in treatment arm 2
Keywords
Adenocarcinoma, Pancreas, Gemcitabine, Atu027
Medical subject headings
Carcinoma, Pancreatic Ductal, Adenocarcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Atu027 & gemcitabine in lead in safety periodDrug

    Subjects will be treated in a 28-day cycle with Atu027 twice weekly for 4 weeks and gemcitabine once weekly for the first three weeks.

  • Atu027 & gemcitabine in treatment arm 1Drug

    Subjects will be treated in a 28-day cycle with Atu027 and gemcitabine once weekly for three consecutive weeks (on days 1, 8, and 15). During week four no treatment is administered.

    Treatment will be continued in consecutive 28-day cycles until unacceptable toxicity or disease progression occurs.

  • Atu027 & gemcitabine in treatment arm 2Drug

    Subjects will be treated in a 28-day cycle with gemcitabine once weekly (on days 4, 11, and 18) and Atu027 twice weekly (on days 1, 4, 8, 11, 15, 18, 22, and 25). The 28-day combination cycle is followed by a 28-day gemcitabine monotherapy cycle.

    Treatment will be continued in consecutive 28-day cycles until unacceptable toxicity or disease progression occurs.

Study groups in NCT01808638
Study groupRoleWhat they receive
Lead in safety periodOtherCohort of three subjects with non-pancreatic cancer for whom conventional treatment options have failed, will be treated. If one of the subjects in the safety cohort experiences an unacceptable toxicity, the safety cohort is expanded to six subjects.
Receives: Drug: Atu027 & gemcitabine in lead in safety period
Treatment arm 1ExperimentalSubjects with advanced pancreatic cancer will be treated.
Receives: Drug: Atu027 & gemcitabine in treatment arm 1
Treatment arm 2ExperimentalSubjects with advanced pancreatic cancer will be treated.
Receives: Drug: Atu027 & gemcitabine in treatment arm 2

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of subjects with adverse events

    Time frame will be 18 weeks if patient will be withdrawn after 3 cycles because of disease progression or toxicity.

    Measured: Baseline till follow up visit 1 (18 weeks)

  2. Subject physical examination

    Additional time frames in arm 1: 8 days after baseline. Additional time frames in arm 2 and safety cohort (cycle 1 only): 4 and 15 days after baseline.

    Measured: At baseline; later on in 4 week intervals till last follow up visit (1 year);

  3. Measuring of subject vital signs and body weight

    End of treatment visit will be after 13 weeks only when patient is withdrawn after 3 cycles.

    Additional time frames in arm 1: 8 days after baseline. Additional time frames in arm 2 and safety cohort (cycle 1 only): 4 and 15 days after baseline.

    Measured: At baseline; end of treatment (13 weeks); later on in 4 week intervals till last follow up visit (1 year)

  4. Performance of 12-lead ECG

    End of treatment visit will be after 13 weeks only when patient is withdrawn after 3 cycles.

    Additional time frames in arm 1: 8 days after baseline. Additional time frames in arm 2 and safety cohort (cycle 1 only): 4 and 15 days after baseline.

    Measured: At baseline; later on in 4 week intervals till end of treatment (13 weeks)

  5. Assessment of clinically significant laboratory parameters outside normal range

    Additional time frames in arm 1: During treatment on days 1, 8, 15 of each cycle.

    Additional time frames in arm 2 and safety cohort (cycle 1 only): During treatment on days 1, 4, 8, 11, 15, 18, 22, 25 of each cycle.

    Measured: At baseline; at end of treatment (week 13 if patient withdrawn after 3 cycles); at follow up visit 1 (week 18 if patient withdrawn after 3 cycles); at each follow up visit till end of trial (1 year)

  6. Maximum concentration (Cmax), area under the curve (AUC), time to maximum concentration (tmax), and half life (t½) of the Atu027 siRNA single strand (A-strand), and of AtuFect01 and the helper lipid DPyPE

    Additional time frames in arm 1: During cycles 1 and 2 of treatment on days 1, 8, 15 of each cycle; in cycle 3 and following only on day 1; Additional time frames in arm 2 and safety cohort (cycle 1 only): During the first treatment cycle on days 1, 4, 8, 11, 15, 18; in cycle 3 and following odd numbered cycles only on day 1; in all even numbered cycles no samples are taken.

    Pharmacokinetics will be assessed in subjects of the safety cohort and in the first 4 subjects per treatment arm.

    Measured: At end of treatment (week 13 if patient withdrawn after 3 cycles); at follow up visit 1 (week 18 if patient withdrawn after 3 cycles)

Secondary outcomes (6)

  1. Objective response rate

    Response will be assessed by RECIST Version 1.1 using abdominal magnetic resonance imaging (MRI) or computed tomography (CT) scans.

    An objective response is defined when the overall response is complete response (CR), partial response (PR), or stable disease (SD).

    Measured: At baseline and in 8 week intervals till end of trial (1 year)

  2. Progression-free survival and overall survival

    Progression-free survival and overall survival, based on the objective response definition will be analyzed using Kaplan-Meier methods.

    Measured: From baseline in 8 week intervals till end of trial (1 year).

  3. ECOG performance score

    Additional time frames: During treatment on day 1 of each cycle.

    The ECOG performance status, and its change from baseline, will be summarized descriptively by visit and treatment arm. The ECOG performance status will also be assessed during the 1 year follow-up period of the study and results including changes to baseline will be summarized.

    Measured: At baseline; at end of treatment (13 weeks if patient withdrawn after 3 cycles); at follow up visit 1 (18 weeks if patient withdrawn after 3 cycles); at each following follow up visit till end of trial (1 year)

  4. Biomarker response

    Serum protein markers and circulating microRNA will be analyzed and changes to baseline will be summarized descriptively by treatment arm.

    Measured: At baseline; at day 1 of cycle 3; end of treatment (13 weeks if patient withdrawn after 3 cycles); follow up visit 1 (18 weeks if patient withdrawn after 3 cycles)

  5. Tumor marker response

    Additional time frame: At day 1 of cycle 3 and day 1 of each following second cycle; Tumor markers will be summarized descriptively for each analyzed marker.

    Measured: At baseline; at end of treatment (13 weeks if patient withdrawn after 3 cycles); at follow up visit 1 (18 weeks if patient withdrawn after 3 cycles); at each following follow up visit till end of trial (1 year)

  6. Quality of life

    Different scales of quality of life assessed with the EORTC questionnaire and their changes from baseline will be summarized descriptively by visit and treatment arm.

    Measured: At baseline; at day 1 of all cycles except cycle 1; at end of treatment (week 13 if patient withdrawn after 3 cycles)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Mar 2013 (estimated)
  2. Study startMar 2013
  3. Primary completionAug 2015
  4. Study completionJan 2016

Resources

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 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
29 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01808638
Sponsor's protocol ID
Atu027-I-02
Other IDs
2012-004429-26
Acronym
Atu027-I-02
Status last verified
Mar 2016
First submitted
4 Mar 2013
Last updated
11 Mar 2016
Results posted
No
Data monitoring committee
Yes

Publications

  • Schultheis B, Strumberg D, Kuhlmann J, Wolf M, Link K, Seufferlein T, Kaufmann J, Feist M, Gebhardt F, Khan M, Stintzing S, Pelzer U. Safety, Efficacy and Pharcacokinetics of Targeted Therapy with The Liposomal RNA Interference Therapeutic Atu027 Combined with Gemcitabine in Patients with Pancreatic Adenocarcinoma. A Randomized Phase Ib/IIa Study. Cancers (Basel). 2020 Oct 26;12(11):3130. doi: 10.3390/cancers12113130.

    PubMed 33114652

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Atu027 & gemcitabine in lead in safety period, Atu027 & gemcitabine in treatment arm 1 and Atu027 & gemcitabine in treatment arm 2 in people with Carcinoma, Pancreatic Ductal, run by Silence Therapeutics GmbH at 9 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 37 inclusion and 32 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 11 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 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 combined 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.

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?

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?

Number of subjects with adverse events (time frame: Baseline till follow up visit 1 (18 weeks)). The study lists 6 primary outcomes in all. 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 NCT01808638, which also lists 1 linked publication.

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 11 Mar 2016.

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