tTF-NGR Phase I Study

NCT02902237 | Completed Phase 1 Results DMC

• 2 other identifiers: UKM12_00182016-003042-85
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Malignant Solid Tumors; Lymphomas

Keywords

tTF-NGR; vascular targeting; CD13; aminopeptidase N; first-in-class phase I study

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) and Dose-limiting Toxicity (DLT)

  DLT will be characterized by clinical, blood and serum monitoring at specified time points before and during study period. AE, SAE, and SUSAR reporting was according to CTCAE 4.0 and GCP guidelines.

  Measures: daily during treatment, weekly during rest periods of 2 weeks, monthly after End of Therapy, up to 3 months.

Secondary Outcomes (1)

• 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]

  1: Tumor blood flow: baseline, 5 h post-dose, at 5 d at each cycle of therapy and 6 months. 2: Pharmacokinetic measures: 0 h, 0.5 h, 1 h, 1.5 h, 3 h, 2.5 h, 3 h, 3.5 h, 4 h, 4.5 h, 5 h post-dose

Study Arms (1)

tTF-NGR

EXPERIMENTAL

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.

Biological: tTF-NGR

Interventions

tTF-NGR BIOLOGICAL

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.

Also known as: truncated tissue factor (tTF)-NGR

tTF-NGR

Eligibility Criteria

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

You may qualify if:

• 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
• ability to understand and provide written informed consent
• written informed consent given

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Hospital Muenster: lead
• Deutsche Krebshilfe e.V., Bonn (Germany): collaborator

Study Sites (1)

University Hospital Muenster

Münster, North Rhine-Westphalia, 48149, Germany

Location

Related Publications (1)

• Schliemann C, Gerwing M, Heinzow H, Harrach S, Schwoppe C, Wildgruber M, Hansmeier AA, Angenendt L, Berdel AF, Stalmann U, Berning B, Kratz-Albers K, Middelberg-Bisping K, Wiebe S, Albring J, Wilms C, Hartmann W, Wardelmann E, Krahling T, Heindel W, Gerss J, Bormann E, Schmidt H, Lenz G, Kessler T, Mesters RM, Berdel WE. First-In-Class CD13-Targeted Tissue Factor tTF-NGR in Patients with Recurrent or Refractory Malignant Tumors: Results of a Phase I Dose-Escalation Study. Cancers (Basel). 2020 Jun 7;12(6):1488. doi: 10.3390/cancers12061488.

  PMID: 32517329 RESULT

MeSH Terms

Conditions

Lymphoma

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Prof. Dr. Wolfgang Berdel, Professor of Medicine
• Organization: Department of Medicine A, University Hospital Muenster, Germany

berdel@uni-muenster.de

+49 251 835

Study Officials

• Christoph Schliemann, Prof.

  University Hospital of Muenster

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Model Details: Single-arm, mono-center, open-label phase I trial with intraindividual dose escalation

Study Record Dates

• First Submitted: September 5, 2016
• First Posted: September 15, 2016
• Study Start: March 1, 2017
• Primary Completion: November 5, 2019
• Study Completion: November 5, 2019
• Last Updated: December 8, 2020
• Results First Posted: December 8, 2020

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data are shared as a publication, June 2020
• Access Criteria: Access to CANCERS necessary

Locations

DE (1)