Phase 1
Completed N=17
tTF-NGR Phase I Study
Malignant Solid Tumors · Lymphoma
Source: ClinicalTrials.gov NCT02902237 ↗
Enrolled (actual)
17
Serious AEs
52.2%
Results posted
Dec 2020
Primary outcomePrimary: Maximum Tolerated Dose (MTD) and Dose-limiting Toxicity (DLT) — 8; 5; 4 Participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Tolerated Dose (MTD) and Dose-limiting Toxicity (DLT) |
8; 5; 4 | — |
| SECONDARY 1: Assessment of Anti-tumor Activity: MRI K-trans in [ 10^-3/Min] and/or CEUS in [Arbitrary Units]; 2: Pharmacokinetic Profile: AUC in [ng*h/mL] |
17; 0; 17; 0 | — |
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.
Data sourced from ClinicalTrials.gov (NCT02902237). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.