ST1968 Intravenous (Weekly) in Solid Tumors

Solid Tumors Clinical Trial

Official title:

Phase I Dose Finding and Pharmacokinetic Study of the Intravenous Camptothecin ST1968 in Patients With Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01748019
• Other study ID #: ST1968-DM-06-001
• Status: Completed
• Phase: Phase 1
• First received: June 12, 2012
• Last updated: December 10, 2012
• Start date: June 2007
• Est. completion date: December 2011

Study information

• Verified date: June 2012
• Source: sigma-tau i.f.r. S.p.A.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Swissmedic
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 62
• Est. completion date: December 2011
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Solid Tumors

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
sigma-tau i.f.r. S.p.A.	Southern Europe New Drug Organization

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	2/6 patients with a Dose Limiting Toxicity (DLT) at the first cycle (21 days)	21 days	Yes
Secondary	Adverse events, physical examination and laboratory tests (hematology and biochemistry) as a measure of safety and tolerability	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)	21 days of each cycle of therapy	Yes
Secondary	Tumor response	objective tumor response based on RECIST criteria	4 weeks	No
Secondary	Tmax, Cmax, AUC0-24, AUC-last, T1/2,CL	full blood and urine PK	21 days	Yes