Safety and Tolerability of AP 12009, Administered I.V. in Patients With Advanced Tumors Known to Overproduce TGF-beta-2

NCT00844064 | Completed Phase 1 DMC

• 1 other identifier: AP 12009-P001
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 10

Brief 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.

Conditions

Pancreatic Neoplasms; Melanoma; Colorectal Neoplasms

Keywords

Pancreatic cancer; Metastatic melanoma; Advanced tumor; Targeted therapy; Antisense; Transforming Growth Factor beta 2; Dose escalation

Outcome Measures

Primary Outcomes (1)

• 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.

Study Arms (1)

AP 12009

EXPERIMENTAL

Drug: AP 12009

Interventions

AP 12009 DRUG

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

AP 12009

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• b. Melanoma: Histologically or cytologically confirmed diagnosis, stage III or IV (AJCC, UICC).
• c. Colorectal cancer: Histologically or cytologically confirmed diagnosis, stage III or IV (AJCC, UICC), excluded from the last cohort.
• 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.

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Isarna Therapeutics GmbH: lead

Study Sites (10)

Universitätsmedizin Berlin Charité

Berlin, 10117, Germany

Location

Universitätsklinik und Poliklinik für Innere Medizin I

Halle, 06120, Germany

Location

Hautklinik der Ruprecht-Karls-Universität Heidelberg

Heidelberg, 69115, Germany

Location

Universitätsklinikum Schleswig-Holstein

Kiel, 24105, Germany

Location

Krankenhaus rechts der Isar, II. Medizinische Klinik und Poliklinik

München, 81675, Germany

Location

Universität Münster, Klinik und Poliklinik für Hautkrankheiten

Münster, 48149, Germany

Location

Klinik und Poliklinik für Innere Medizin I

Regensburg, 93042, Germany

Location

Klinik und Poliklinik für Dermatologie

Regensburg, 93053, Germany

Location

Universitäts-Hautklinik, Sektion Dermatologische Onkologie

Tübingen, 72076, Germany

Location

Universitätsklinikum Ulm, Zentrum für Innere Medizin

Ulm, 89081, Germany

Location

MeSH Terms

Conditions

Pancreatic Neoplasms; Melanoma; Colorectal Neoplasms

Interventions

Trabedersen

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Helmut Oettle, MD

  Charité Berlin Campus Virchow-Klinikum

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: February 12, 2009
• First Posted: February 13, 2009
• Study Start: January 1, 2005
• Primary Completion: November 1, 2011
• Study Completion: November 1, 2011
• Last Updated: February 15, 2019

Record last verified: 2019-02

Locations

DE (10)