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

NCT01808638 | Completed Phase 1 DMC

• 2 other identifiers: Atu027-I-022012-004429-26
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 9

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

Keywords

Adenocarcinoma; Pancreas; Gemcitabine; Atu027

Outcome Measures

Primary Outcomes (6)

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  Time frame will be 18 weeks if patient will be withdrawn after 3 cycles because of disease progression or toxicity.

  Baseline till follow up visit 1 (18 weeks)

• 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.

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

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  End of treatment visit will be after 13 weeks only when patient is withdrawn after 3 cycles.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

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

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  End of treatment visit will be after 13 weeks only when patient is withdrawn after 3 cycles.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

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

• 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.

  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)

• 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.

  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)

• Objective response rate

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

• Progression-free survival and overall survival

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

• ECOG performance score

  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)

• Biomarker response

  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)

• Tumor marker response

  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)

Study Arms (3)

Lead in safety period

OTHER

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.

Drug: Atu027 & gemcitabine in lead in safety period

Treatment arm 1

EXPERIMENTAL

Subjects with advanced pancreatic cancer will be treated.

Drug: Atu027 & gemcitabine in treatment arm 1

Treatment arm 2

EXPERIMENTAL

Subjects with advanced pancreatic cancer will be treated.

Drug: Atu027 & gemcitabine in treatment arm 2

Interventions

Atu027 & gemcitabine in lead in safety period 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.

Lead in safety period

Atu027 & gemcitabine in treatment arm 1 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 1

Atu027 & gemcitabine in treatment arm 2 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.

Treatment arm 2

Eligibility Criteria

• Age: 18 Years - 84 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Silence Therapeutics GmbH: lead
• Granzer Regulatory Consulting & Services: collaborator
• FGK Clinical Research GmbH: collaborator

Study Sites (9)

Charité - Universitätsmedizin Berlin Charité Centrum für Tumormedizin

Berlin, 13353, Germany

Location

Klinikum Dortmund gGmbH Medizinische Klinik Mitte

Dortmund, 44137, Germany

Location

Universitätsklinikum Freiburg, Innere Medizin II

Freiburg im Breisgau, 79106, Germany

Location

Medizinische Klinik III - Hämatologie/Onkologie Marienhospital Herne

Herne, 44625, Germany

Location

Klinikum Kassel GmbH Medizinischen Klinik IV;Onkologie,

Kassel, 34125, Germany

Location

Klinikum Nürnberg Nord Medizinische Klinik 5

Nuremberg, 90419, Germany

Location

Klinik und Poliklinik für Innere Medizin I Universitätsklinikum Regensburg

Regensburg, 93042, Germany

Location

Klinikum Stuttgart Klinik Hämatologie, Onkologie und Palliativmedizin

Stuttgart, 70174, Germany

Location

Universitätsklinikum Ulm Zentrum für Innere Medizin

Ulm, 89061, Germany

Location

Related Publications (1)

• 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.

  PMID: 33114652 DERIVED

MeSH Terms

Conditions

Carcinoma, Pancreatic Ductal; Adenocarcinoma

Interventions

Atu027; Gemcitabine; Lead

Condition Hierarchy (Ancestors)

Carcinoma, Ductal; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Ductal, Lobular, and Medullary; Pancreatic Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Metals, Heavy; Elements; Inorganic Chemicals; Metals

Study Officials

• Dirk Strumberg, Prof.Dr.med.

  Medizinische Klinik III - Hämatologie/Onkologie Marienhospital Herne

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2013
• First Posted: March 11, 2013
• Study Start: March 1, 2013
• Primary Completion: August 1, 2015
• Study Completion: January 1, 2016
• Last Updated: March 11, 2016

Record last verified: 2016-03

Locations

DE (9)