ST1968 Intravenous (Weekly) in Solid Tumors

NCT ID: NCT01748019

Last Updated: 2012-12-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 62 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-06-30
• Study Completion Date: 2011-12-31

Brief Summary

ST1968 is a novel camptothecin derivative which interacts with topoisomerase I-DNA complex, inducing S-Phase specific cytotoxicity. It is endowed with a potent antitumor activity and an increased Therapeutic Index with respect to the clinically used analogues (i.e.irinotecan and topotecan) in some xenograft models (ovary, colon, head & neck, cervix). Anti-tumor activity has been also noted in platinum resistant ovarian cell xenografts and in topoisomerase I mutant prostate cell lines. The acceptable toxicity profile in animals and the activity in camptothecin-resistant cell lines make ST1968 a good candidate for clinical trials.

Detailed Description

Multicenter, open label, uncontrolled Phase I pharmacokinetic trial to determine the Maximum Tolerated Dose (MTD) of ST1968 given intravenously (I.V.) once every week for 2 consecutive weeks every 3 weeks and the MTD of ST1968 given I.V. once every 3 weeks. A starting dose of 1.5mg/m2 given as a flat dose of 2.5mg is defined, given once on Day 1, Day 8 every 21 Days (D1, D8 Q21D schedule), over 2 h. Starting dose for the Day 1 every 21 Days (D1 Q21D schedule) has to be determined from the MTD of D1, D8 Q21D schedule.

Plasma, urine pharmacokinetics in all patients (minimum of 3 pts for each cohort) during the first cycle of treatment and in at least 6 patients at the Recommended Dose (RD).

During the study any hints of anti-tumor activity will also be evaluated by RECIST criteria.

Conditions

Solid Tumors

Keywords

ST1968; Camptothecin; Solid tumors; Topoisomerase I

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ST1968

ST1968 once a week for 2 weeks every 3 weeks (protocol amendment: once every 3 weeks

--------------------------------------------------------------------------------

Group Type: EXPERIMENTAL

ST1968

Intervention Type: DRUG

ST1968 once a week for 2 weeks every 3 weeks (protocol amendment: once every 3 weeks

Interventions

ST1968

ST1968 once a week for 2 weeks every 3 weeks (protocol amendment: once every 3 weeks

Intervention Type: DRUG

Other Intervention Names

Namitecan

Eligibility Criteria

Inclusion Criteria

• Histological/cytological diagnosis of solid tumors for which therapy of proven efficacy does not exist.
• Preferably measurable disease
• ECOG performance status ≤ 1.
• Age ≥ 18 years.
• Ongoing toxicity associated with prior anticancer therapy ≤ grade 1 (NCI-CTCAE V3.0).
• Maximum of 2 prior chemotherapy lines for advanced disease (not including neoadjuvant or adjuvant chemotherapy)
• Adequate hematological, liver and renal function
• Hemoglobin ≥ 9 g/dl; ANC ≥ 1.5 x 109/L; platelets ≥ 100 x 109/L;
• Serum bilirubin ≤ upper normal limit (UNL). ALT, AST ≤ UNL but ≤ 2.5 x UNL in case of liver metastases; alkaline phosphatase (liver isoenzyme fraction) ≤ UNL or ≤ 1.5xULN in case of liver metastases; albumin within normal limits;
• Creatinine ≤1.5 mg/dl or calculated creatinine clearance ≥ 60 ml/min.
• Life expectancy of at least 3 months
• Capacity of understanding the nature of the trial and giving written informed consent.

Exclusion Criteria

• Less than 4 weeks since last chemotherapy, radiotherapy or prior investigational therapy. Less than 2 weeks since last hormone or immunotherapy or signal transduction therapy.
• Active infection.
• Presence of cirrhosis or chronic hepatitis
• Presence of serious cardiac (congestive heart failure, angina pectoris, myocardial infarction within one year prior to study entry, uncontrolled hypertension or arrhythmia), neurological or psychiatric disorder.
• Presence of uncontrolled intercurrent illness or any condition which in the judgement of the investigator would place the subject at undue risk or interfere with the results of the study.
• Symptomatic brain metastases (this does not include primary brain tumors) or leptomeningeal disease.
• Pregnancy or lactation or unwillingness to use adequate method of birth control

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Southern Europe New Drug Organization

OTHER

Sponsor Role: collaborator

sigma-tau i.f.r. S.p.A.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dagmar Hess, MD

Role: STUDY_CHAIR

Kantonsspital St. Gallen, 9700 St. Gallen - Switzerland

Other Identifiers

ST1968-DM-06-001

Identifier Type: -

Identifier Source: org_study_id