Study of Oral Vorinostat in Combination With Topotecan in Patients With Chemosensitive Recurrent Small Cell Lung Cancer (SCLC) - Full Text View

Sponsored by:	Istituto Clinico Humanitas
Information provided by:	Istituto Clinico Humanitas
ClinicalTrials.gov Identifier:	NCT00697476

Purpose

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

Condition	Intervention	Phase
Small Cell Lung Cancer	Drug: topotecan, vorinostat	Phase I Phase II

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Topotecan hydrochloride Topotecan Suberoylanilide hydroxamic acid Disulfiram

U.S. FDA Resources

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

Further study details as provided by Istituto Clinico Humanitas:

Primary Outcome 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) ] [ Designated as safety issue: Yes ]

Secondary Outcome 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 ] [ Designated as safety issue: No ]

Estimated Enrollment:

78

Intervention Details:

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00697476

Contacts

Contact: Armando Santoro, MD	39-02-8224 ext 4080	armando.santoro@humanitas.it
Contact: Raffaele Cavina, MD	39-02-8224 ext 4588	raffaele.cavina@humanitas.it

Locations

Italy, Milan
Istituto Clinico Humanitas
Rozzano, Milan, Italy, 20089

Sponsors and Collaborators

Istituto Clinico Humanitas

Investigators

Principal Investigator:

Armando Santoro, MD

Istituto Clinico Humanitas

More Information

Responsible Party:	Istituto Clinico Humanitas ( Armando Santoro, MD )
Study ID Numbers:	ONC-2007-002, EUDRACT
Study First Received:	June 11, 2008
Last Updated:	December 1, 2008
ClinicalTrials.gov Identifier:	NCT00697476
Health Authority:	Italy: Ministry of Health

Keywords provided by Istituto Clinico Humanitas:

second line chemotherapy

Study placed in the following topic categories:

Disulfiram
Thoracic Neoplasms
Carcinoma, Neuroendocrine
Vorinostat
Recurrence
Carcinoma
Neuroendocrine Tumors
Carcinoma, Small Cell
Neuroectodermal Tumors

Respiratory Tract Diseases
Lung Neoplasms
Lung Diseases
Neoplasms, Germ Cell and Embryonal
Neuroepithelioma
Topotecan
Adenocarcinoma
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Anticarcinogenic Agents
Anti-Inflammatory Agents
Respiratory Tract Neoplasms
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Neoplasms, Nerve Tissue
Enzyme Inhibitors
Protective Agents
Pharmacologic Actions

Neoplasms
Neoplasms by Site
Sensory System Agents
Analgesics, Non-Narcotic
Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal
Peripheral Nervous System Agents
Analgesics
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 15, 2009