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ST1968 Intravenous (Weekly) in Solid Tumors

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01748019
First Posted: December 12, 2012
Last Update Posted: December 12, 2012
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Southern Europe New Drug Organization
Information provided by (Responsible Party):
sigma-tau i.f.r. S.p.A.
  Purpose
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.

Condition Intervention Phase
Solid Tumors Drug: ST1968 Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Dose Finding and Pharmacokinetic Study of the Intravenous Camptothecin ST1968 in Patients With Solid Tumors

Further study details as provided by sigma-tau i.f.r. S.p.A.:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of ST1968 given I.V. once every week for 2 consecutive weeks every 3 weeks and MTD of ST1968 given I.V. once every 3 weeks [ Time Frame: 21 days ]
    2/6 patients with a Dose Limiting Toxicity (DLT) at the first cycle (21 days)


Secondary Outcome Measures:
  • Adverse events, physical examination and laboratory tests (hematology and biochemistry) as a measure of safety and tolerability [ Time Frame: 21 days of each cycle of therapy ]
    safety assessments (routine physical examinations and laboratory evaluations) and severity of adverse events based on the NCI-Common Terminology Criteria for Adverse Events V. 3.0 (NCI-CTCAE)

  • Tumor response [ Time Frame: 4 weeks ]
    objective tumor response based on RECIST criteria

  • Tmax, Cmax, AUC0-24, AUC-last, T1/2,CL [ Time Frame: 21 days ]
    full blood and urine PK


Enrollment: 62
Study Start Date: June 2007
Study Completion Date: December 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ST1968

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

Drug: ST1968
ST1968 once a week for 2 weeks every 3 weeks (protocol amendment: once every 3 weeks
Other Name: Namitecan

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.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01748019


Sponsors and Collaborators
sigma-tau i.f.r. S.p.A.
Southern Europe New Drug Organization
Investigators
Study Chair: Dagmar Hess, MD Kantonsspital St. Gallen, 9700 St. Gallen - Switzerland
  More Information

Responsible Party: sigma-tau i.f.r. S.p.A.
ClinicalTrials.gov Identifier: NCT01748019     History of Changes
Other Study ID Numbers: ST1968-DM-06-001
First Submitted: June 12, 2012
First Posted: December 12, 2012
Last Update Posted: December 12, 2012
Last Verified: June 2012

Keywords provided by sigma-tau i.f.r. S.p.A.:
ST1968
Camptothecin
Solid tumors
Topoisomerase I

Additional relevant MeSH terms:
Camptothecin
Namitecan
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action