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

NCT ID: NCT01808638

Last Updated: 2016-03-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-03-31
• Study Completion Date: 2016-01-31

Brief 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.

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.

Conditions

Carcinoma, Pancreatic Ductal

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Lead in safety period

Cohort 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.

Group Type: OTHER

Atu027 & gemcitabine in lead in safety period

Intervention Type: DRUG

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.

Treatment arm 1

Subjects with advanced pancreatic cancer will be treated.

Group Type: EXPERIMENTAL

Atu027 & gemcitabine in treatment arm 1

Intervention Type: DRUG

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.

Treatment arm 2

Subjects with advanced pancreatic cancer will be treated.

Group Type: EXPERIMENTAL

Atu027 & gemcitabine in treatment arm 2

Intervention Type: DRUG

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.

Interventions

Atu027 & gemcitabine in lead in safety period

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.

Intervention Type: DRUG

Atu027 & gemcitabine in treatment arm 1

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.

Intervention Type: DRUG

Atu027 & gemcitabine in treatment arm 2

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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
• 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.

Exclusion Criteria

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
• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 84 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Granzer Regulatory Consulting & Services

OTHER

Sponsor Role: collaborator

FGK Clinical Research GmbH

INDUSTRY

Sponsor Role: collaborator

Silence Therapeutics GmbH

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dirk Strumberg, Prof.Dr.med.

Role: PRINCIPAL_INVESTIGATOR

Medizinische Klinik III - Hämatologie/Onkologie Marienhospital Herne

Locations

Charité - Universitätsmedizin Berlin Charité Centrum für Tumormedizin

Berlin, , Germany

Klinikum Dortmund gGmbH Medizinische Klinik Mitte

Dortmund, , Germany

Universitätsklinikum Freiburg, Innere Medizin II

Freiburg im Breisgau, , Germany

Medizinische Klinik III - Hämatologie/Onkologie Marienhospital Herne

Herne, , Germany

Klinikum Kassel GmbH Medizinischen Klinik IV;Onkologie,

Kassel, , Germany

Klinikum Nürnberg Nord Medizinische Klinik 5

Nuremberg, , Germany

Klinik und Poliklinik für Innere Medizin I Universitätsklinikum Regensburg

Regensburg, , Germany

Klinikum Stuttgart Klinik Hämatologie, Onkologie und Palliativmedizin

Stuttgart, , Germany

Universitätsklinikum Ulm Zentrum für Innere Medizin

Ulm, , Germany

Countries

Germany

References

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.

Reference Type: DERIVED

PMID: 33114652 (View on PubMed)

Other Identifiers

2012-004429-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

Atu027-I-02

Identifier Type: -

Identifier Source: org_study_id