A Trial Evaluating the Pharmacokinetics and Mode of Action of EndoTAG®-1 in Tumor Patients With Hepatic Metastases

An Open-label, Uncontrolled, Phase II Trial Evaluating the Single-dose and Steady-state Pharmacokinetics of EndoTAG®-1 and Its Effect on the Blood Supply and the Angiogenesis of Hepatic Metastases in Patients With a Carcinomatous Primary Tumor Other Than Hepatocellular (HCC), Biliary or Bile Duct Carcinoma

The primary objective of study CT 4003 is to assess the behavior of EndoTAG®-1 in the body (making a so-called pharmacokinetic profile). Therefore, the course of the drug in the body is examined, i.e. the amount and speed of the drug uptake as well as the distribution and the elimination of the drug is being investigated. Further objectives of the study are to assess the effect of EndoTAG®-1 on liver metastases concerning size and blood supply measured by imaging techniques (contrast-enhanced ultrasound and magnetic resonance imaging as well as duplex sonography) and to assess the effect on blood markers which are indicators for the destruction and neoplasm of blood vessels (so-called markers of angiogenesis).

Study Overview

• Status: Completed
• Conditions: Neoplasm Metastasis; Liver Cancer
• Intervention / Treatment: Drug: EndoTAG®-1

Detailed Description

Liver metastases are among the most frequent neoplasms of the liver and represent a quite uniform clinical entity regardless from which carcinoma they originate. The treatment is dependent on number and size of the hepatic lesions but still, none of the therapeutic options leads to satisfying results. The growth of tumors and metastases is dependent on blood vessels, which supply the tumors and metastases with nutrients. Liver metastases, independent from which original tumor they come from, are especially well supplied with blood. The aim of the treatment with the investigational medicinal product EndoTAG®-1 is to target the blood vessels, which supply the metastases, and destroy them. Consequently, the metastases themselves will be damaged.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Baden-Würtemberg
    • Freiburg Im Breisgau, Baden-Würtemberg, Germany, 79106
      • Klinik für Internistische Onkologie in der KTB Klinik für Tumorbiologie an der Albert-Ludwigs-Universität Freiburg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Unresectable hepatic metastases of a carcinomatous origin with exception of HCC, biliary or bile duct carcinoma
• At least one measurable hepatic metastases > 20 mm in diameter (measured in MRI)
• Last application of palliative chemotherapy (drug dependent on the primary tumor) at least 7 days ago
• Gender: male and female (at least 6 individuals of each gender)
• Age >= 18 years
• Negative pregnancy test (females of childbearing potential)
• Willingness to perform double-barrier-contraception during the study and for 6 month post study medication
• ECOG performance status 0,1 or 2
• Assumed life expectancy of > 3 month
• Signed informed consent

Exclusion Criteria:

• History of significant liver pathology (other than metastases, e.g. cirrhosis of the liver, PSC, PBC) or liver transplantation
• Laboratory tests (hematology, chemistry) outside specific limits:
• ANC <= 1.0 x 10^9/L
• Platelets <= 100 x 10^9/L
• Hb <= 9.0 g/dL (<= 5.6 mmol/L)
• Total Bilirubin > 2.0 mg/dL
• Serum Creatinine > 1.5 mg/dL
• Renal insufficiency with a GFR < 60 mL/min
• Currently ongoing taxane-containing palliative chemotherapy regimen or history of taxane administration within 4 weeks prior to study entry
• Pregnancy or nursing status
• Positive HIV, HBV or HCV testing
• The patient has a contraindication for MRI or CEUS according to accepted clinical guidelines
• Known hypersensitivity to any component of the EndoTAG®-1 formulation, gadolinium-based MR-contrast media or sulphur hexafluoride
• Claustrophobia or history of active or significant neurological disorder and/or psychiatric disorder that would prohibit the understanding and giving of informed consent, or would interfere in the clinical and radiological evaluation of the patient during the trial
• Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational drug within 30 days prior to study entry

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: EndoTAG®-1; EndoTAG®-1 22 mg/m² twice weekly

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetic profile	Last patient out

Secondary Outcome Measures

Outcome Measure	Time Frame
Tumor response, Tumor perfusion, Soluble markers of angiogenesis, Pharmacodynamics, Safety	Last patient out

Collaborators and Investigators

• Sponsor: MediGene
• Investigators: Principal Investigator: Klaus Mross, PD, Klinik für Tumorbiologie an der Albert-Ludwigs-Universität Freiburg

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (Actual): September 1, 2009
• Study Completion (Actual): September 1, 2009

Study Registration Dates

• First Submitted: October 9, 2007
• First Submitted That Met QC Criteria: October 9, 2007
• First Posted (Estimate): October 10, 2007

Study Record Updates

• Last Update Posted (Estimate): February 9, 2010
• Last Update Submitted That Met QC Criteria: February 8, 2010
• Last Verified: November 1, 2009

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Angiogenesis; Pharmacodynamics; EndoTAG-1; Hepatic metastases; Metastases of the liver
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis; Neoplasms, Second Primary
• Other Study ID Numbers: CT 4003