ST1968 Intravenous (Weekly) in Solid Tumors

Sigma-Tau Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Solid Tumors

Treatments: Drug: ST1968

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01748019

ST1968-DM-06-001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 62 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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62 participants in 1 patient group

ST1968

Experimental group

Description:

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

Treatment:

Drug: ST1968