Official Title: “Phase I-II Study of Oral Suberoylanilide Hydroxamic Acid (Vorinostat) in Combination With Topotecan in Patients With Chemosensitive Recurrent Small Cell Lung Cancer (SCLC)”

The purpose of this study is to evaluate the maximum tolerated dose, the activity and the safety profile of the combination of vorinostat and topotecan in patients with recurrent small cell lung cancer

Study Type: Interventional

Study Design: Treatment, Open Label, Single Group Assignment, Safety/Efficacy Study

Intervention(s) in this Clinical Trial

• Drug: topotecan, vorinostat
  • Phase I study: vorinostat will be administered daily for a number of days per cycle variable from 7 to 14 according to the level of dose escalation; topotecan will be administered I.V. for 5 consecutive days every 3 weeks. Three patients will be entered at each dose level. If none of the first 3 patients at a dose level experiences a DLT after 1 cycle (21 days) then 3 new patients may be entered at the next higher dose level. If 1 of 3 patients experiences a DLT, up to 3 more patients are started at that same dose level (total n=6). If 2 or more experience a DLT, no further patients are started at that dose. The MTD is one dose level below dose at which ³ 2 patients experience DLT. Phase II study: Patients will receive treatment at the recommended dose established by phase I part of the trial, for a maximum of 6 cycles or until disease progression, unacceptable toxicity or patient's refusal.

Primary Measures

• Maximum tolerated dose of the combination as the recommended dose for phase II trial [Phase I]; objective response rate of the combination [Phase II]; toxicity and safety profile of the combination [Phase II]
  • Time Frame: Limiting tolerated dose (Phase I); efficacy/toxicity after the inclusion of the last patient (Phase II)
    Safety Issue?: Yes

Secondary Measures

• To assess the antitumor activity of the combination in terms of time to progression (TTP) and overall survival (OS) [Phase II]
  • Time Frame: After the follow up period
    Safety Issue?: No

Inclusion Criteria:

• Histologically or cytologically proven diagnosis of SCLC;
• Limited or extensive-stage disease in patients who have received a single chemotherapy regimen or combined modality (chemotherapy + chest radiotherapy) regimen and relapsed after completion of first-line chemotherapy (sensitive relapse);
• Age >/= 18 years;
• ECOG Performance Status 0-2;
• Life expectancy of at least 12 weeks;
• Measurable lesions according to RECIST criteria;
• Adequate cardiac, hepatic, renal, and bone marrow function;
• Written informed consent.

Exclusion Criteria:

• Prior treatment with an HDAC inhibitor;
• Symptomatic and/or unstable pre-existing brain metastases;
• Superior Vena Cava Syndrome;
• Spinal cord compression;
• Severe or uncontrolled medical diseases (Hypertension, diabetes, congestive heart failure, myocardial infarction within 6 months of study, chronic renal disease, or active uncontrolled infections);
• Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal cell carcinoma or cervical cancer in situ;
• Pregnant or breastfeeding women.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Istituto Clinico Humanitas

Overall Clinical Trial Officials and Contacts

Armando Santoro, MD Principal Investigator Istituto Clinico Humanitas  

Overall Contact: Armando Santoro, MD 39-02-8224 armando.santoro@humanitas.it

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00697476

Study ID Number: ONC-2007-002

ClinicalTrials.gov Identifier: NCT00697476

Health Authority: Italy: Ministry of Health