tTF-NGR Phase I Study
Condition: Malignant Solid Tumors; Lymphomas
MeSH terms: Lymphoma
Intervention: tTF-NGR
Intervention description: tTF-NGR will be given as 1-hour infusion via central venous access once daily for 5 days with a subsequent rest period of 2 weeks and following cycles with dose escalation of 0.5 mg/m2 upon judgement of tolerability and therapeutic activity. Starting dose will be 1 mg/m2/day. Dose-escalation is stopped before the maximum number of 8 escalation steps if tumor response, tumor progression or a Dose-Limiting Toxicity (DLT) is observed.
Intervention MeSH terms: Thromboplastin
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: Single-arm, mono-center, open-label phase I trial with intraindividual dose escalation
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: tTF-NGR; vascular targeting; CD13; aminopeptidase N; first-in-class phase I study

Summary:

      In this phase I clinical trial cancer patients suffering from solid tumors or lymphomas,
      recurring after and/or refractory against standard treatment are treated intravenously (iv)
      with increasing doses of tTF-NGR(tTF= truncated tissue factor; NGR=Asn-Gly-Arg). The
      objectives of this trial are to evaluate the maximum tolerated dose (MTD) and the
      dose-limiting toxicity (DLT) of intravenously (iv) infused daily applications of tTF-NGR for
      5 days every 3 weeks in patients with cancer, who had obtained all standard treatment known
      for their disease entity prior to entry on study. Further objectives are to determine the
      perfusion and vascular volume fraction of measurable tumor lesions versus normal reference
      tissue before and after tTF-NGR application by MRI as a biological surrogate parameter for
      biological activity of the investigational medicinal product (IMP), tTF-NGR, and to obtain
      pharmacokinetic data.
    

Eligibility criteria:

        Inclusion criteria:

          -  age ≥ 18 years

          -  histologically proven or cytologically confirmed solid malignant tumor or malignant
             lymphoma

          -  recurrent or refractory disease after standard therapy and with no known curative or
             survival-prolonging treatment options according to the judgement of the investigators

          -  life expectancy of at least 6 weeks according to the judgement of the investigators

          -  Karnofsky performance status ≥ 50

          -  measurable disease with at least one marker-lesion measurable in 2 dimensions by
             Vascular Volume-Fraction-MRI and/or CEUS.

          -  adequate bone marrow function with absolute neutrophil count > 1000/microliter and
             platelet count > 50/nl

          -  normal global coagulation parameters (Quick, partial thromboplastin time (PTT),
             thrombin time (TZ), fibrinogen), no prophylactic anticoagulation

          -  ability to understand and provide written informed consent

          -  adequate liver function (total bilirubin < 3x the upper normal limit (ULN), serum
             glutamic pyruvic transaminase/serum glutamic-oxaloacetic transaminase (SGPT/SGOT) < 3x
             ULN)

          -  adequate renal function (serum creatinine < 3x ULN)

          -  no history of coronary heart disease, stroke, transitory ischemic attacks, pulmonary
             embolism, or deep vein thrombosis

          -  time elapsed from previous therapy (including other IMPs) ≥ 3 weeks with recovery from
             side effects

          -  exclusion of central nervous system (CNS) disease and CNS vascular abnormalities by
             MRI

          -  ability to understand and provide written informed consent

          -  written informed consent given

          -  for female patients with child-bearing potential exclusion of pregnancy by adequate
             testing within 48 hours prior to entry on study

          -  females of childbearing potential as well as fertile males must agree to use a highly
             effective form of contraception (Pearl Index < 1) during the study and for 120 days
             following the last dose of the IMP

        Exclusion criteria:

          -  clinically significant unrelated illness which in the judgement of the investigators
             could compromise the patient's ability to tolerate the IMP or be likely to interfere
             with the study procedures or results

          -  known hypersensitivity reactions to prior application of E. coli-derived material

          -  women with breast-feeding activity

          -  concomitant use of any other investigational agent (agent for which there is currently
             no approved indication from regulatory authorities)

          -  clinical application of any other drug with known anti tumor activity

          -  prophylactic anticoagulation within the last 3 days

        NOTE: Since this is a phase I study for end-stage cancer patients, patients who would be
        excluded from the protocol strictly for laboratory abnormalities only can be included at
        the Investigator's discretion. This will be documented as an exception to the criteria and
        will be signed and filed in the CRF and the Trial Master File.