Dose Escalation Study of TriN2755 in Advanced Solid Tumors and Sarcomas

• Status: Unknown status
• Trial end date: 2012-01-01
• Target enrollment: 0
• Participant gender: All

Summary

This is an open-label, parallel-group, two-center, safety, activity and pharmacokinetic study of TriN 2755 given at increasing dose levels as intravenous infusions administered over 4 hours. The study is divided into two parts: Part I a dose escalation phase and Part II an extension phase.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Trin Therapeutics GmbH
• Collaborators: Assign Data Management and Biostatistics GmbH; Central European Society for Anticancer Drug Research; University Hospital, Essen

Criteria

Inclusion Criteria:

• Male or female patients of age > 18 years

• Patients with a histologically / cytologically confirmed diagnosis of advanced solid tumor or sarcoma for which a treatment of proven efficacy does not exist or an established treatment(s) had failed

• Measurable or non-measurable disease according to RECIST v1.0 criteria. Patients should have at least one measurable lesion or disease which is non-measurable but can clearly be evaluated for response

• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2

• Life expectancy of at least 3 months

• Ability to understand the nature of the study and willingness to sign a written informed consent document

• Willingness and ability to comply with the study protocol for the duration of the study

Exclusion Criteria:

• Any lymphoma or other hematological tumors

• Known brain metastases

• Earlier history of other tumors, except non melanoma-skin cancer or in situ cervical carcinoma curatively excised

• Major surgery within 4 weeks prior to treatment start

• Extensive radiotherapy, within 2 weeks of treatment start, or cytotoxic chemotherapy or limited radiotherapy within 2 weeks of treatment start

• Unresolved toxicity from prior chemotherapy (including approved and experimental drugs)

• Any of the following abnormal baseline hematological values:

• Hb < 10g/dl,

• WBC < 3.0 x 109/l Neutrophils < 1.5 x 109/l

• Platelets < 100 x 109/l

• Any of the following abnormal baseline liver function tests:

• Serum bilirubin > 1.5 x upper normal limit, > 3 x if due to tumor

• ALAT and/or ASAT > 2.5 x upper normal limit, > 5 x if due to tumor

• The following abnormal baseline renal function test:

• Serum creatinine > 1.5 mg/dl

• Creatinine clearance < 50 ml/min

• All clinically relevant cardiovascular abnormalities (i.e. myocardial infarction within the prior 6 months, cardiac arrhythmia requiring medication, uncontrolled hypertension, abnormal cardiac function (* class II of NYHA classification), cardiac failure or non compensated active heart disease (* class II of NYHA classification)

• Neurologic: symptomatic motor or sensory neurotoxicity grade 2 NCI CTC

• Primary tumor associated with central nervous system-related symptoms interfering with the informed consent or with the study

• History of psychiatric disabilities, seizures or central nervous system disorders, which is considered to be clinically significant by the investigator and could interfere with informed consent or adequate follow-up

• Major fluid effusions (e.g. ascites, pleural effusion), or clinically relevant blood loss

• Interstitial pneumonia or lung fibrosis

• History or presence of thromboses or clotting disorders

• Concomitant medication for non-vital indications with known hepatotoxic or nephrotoxic potential (e.g, aminoglycoside antibiotics)

• Serious (Grade 3-4) uncontrolled intercurrent infections

• Any history of alcohol abuse or drug addiction

• Positive results of virus serology tests (i.e. detection of HBsAg and antibodies to HCV, HIV1, HIV2, CMV and EBV)

• Clinical conditions equal to protocol definitions of DLT

• Participation in any investigational drug study within 30 days preceding treatment start

• Male or pre-menopause female patients unable to practice a medically approved method of contraception during the study and the 3-month period thereafter (all patients potentially fertile)

• Pregnancy or breast feeding women

• Any condition which in the judgment of the investigator would place the subject at undue risk or interfere with the results of the study (e.g. increased medical risks due to non malignant organ or systemic disease or secondary effects of cancer)

• History of allergic reactions attributed to compounds of the same chemical class (dacarbazine, temozolomide) as TriN 2755 or any excipients of IMP

• Mental handicap or legal incapacity