Carboplatin and Etoposide in Combination With Vorinostat for Patients With Extensive Stage Small Cell Lung Cancer

NCT00702962 | Terminated Phase 1 Results DMC

• 1 other identifier: PSHCI 08-005
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

The Phase I portion of the study is to assess the maximum tolerated dose of vorinostat when combined with carboplatin plus etoposide. The Phase II portion is to determine progression-free survival among patients with extensive disease small cell lung cancer receiving carboplatin plus etoposide with vorinostat.

Conditions

Small Cell Lung Cancer

Keywords

lung cancer; small cell lung cancer

Outcome Measures

Primary Outcomes (1)

• Assess Maximum Tolerated Dose of Vorinostat When Combined With Carboplatin and Etoposide of Patients With Extensive Disease SCLC

  To estimate the maximum tolerated dose of vorinostat using a traditional dose escalation schedule ("3 + 3 design). MTD is determined by assessing for specific predefined dose limiting toxicities. A starting dose of vorinostat 200mg was combined with carboplatin and etoposide. Dose escalation went in increments of 100mg (i.e. 300mg, 400mg).

  2 years, not analyzed

Secondary Outcomes (3)

• To Evaluate Overall Survival of Patients With Extensive Disease SCLC Receiving Carboplatin, Etoposide, and a Fixed Dose (300mg) of Vorinostat

  2 years, not analyzed

• Evaluate Objective Response Rate Among Patients With Extensive Disease SCLC Receiving Carboplatin and Etoposide With a Fixed Dose of Vorinostat.

  2 years, not analyzed

• To Assess the Safety Profile and Define the Toxicities of Using a Fixed Dose (300mg) of Vorinostat With Carboplatin and Etoposide

  2 years, not analyzed

Study Arms (1)

Phase I: Vorinostat 200 mg

EXPERIMENTAL

Vorinostat 200 mg PO QD D1-14; Administer with Carbo 6 (AUC) D3; Etoposide 100 mg/m2 D1,2,3 "Vorinostat", "Carboplatin", "Etoposide"

Drug: Vorinostat, Carboplatin, Etoposide

Interventions

Vorinostat, Carboplatin, Etoposide DRUG

Study originally a Phase I standard dose escalation of the study medication Vorinostat with sequential cohorts of 3-6 participants entered to 3 dose levels (200mg, 300mg, 400mg). Dose escalation stopped after participant 1 on dose level 2 due to recently published research identifying an appropriate dosing regimen. A set dose was then to be administered to all subsequent participants. This regimen (a "cycle") consisted of Vorinostat on Day 1 through Day 4, Carboplatin AUC 6 on Day 3, and Etoposide 100 mg/m2 on Day 3 through Day 5. Treatment cycles were repeated every 21 days (3 weeks) for 4 cycles total.

Also known as: Suberoyl anilide hydroxamic acid (SAHA)

Phase I: Vorinostat 200 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed small cell lung cancer.
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>20 mm with conventional techniques or as \>10 mm with CT scan.
• Patients must be chemotherapy naive.
• Previous radiotherapy is allowed only if \< 30% of marrow bearing bones were irradiated and if radiotherapy was completed at least 2 weeks prior to enrollment and the patient has recovered from all adverse effects of prior radiotherapy.
• Age \>18 years.
• Life expectancy of greater than 3 months.
• ECOG performance status \<2 (Karnofsky \>60%).
• Adequate organ and marrow function.
• Women of childbearing potential and men must agree to use adequate contraception (hormonal or double barrier method of birth control) prior to study entry and for the duration of study participation.
• Ability to understand and the willingness to sign a written informed consent document.
• Both men and women of all races and ethnic groups are eligible for this trial.

You may not qualify if:

• Patients who have had chemotherapy or any other investigational agent for any indication within 30 days of study enrollment.
• Patients who have had radiotherapy within 2 weeks, prior to entering the study or those who have not recovered from adverse events due to these therapies.
• Patients with known brain metastases are excluded.
• Patients who have been previously treated with an HDAC inhibitor (use of valproic acid is allowed with a 30-day washout).
• Patients with peripheral neuropathy CTC grade \>2 are excluded.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Any major surgery within 2 weeks prior to enrollment. Minimally invasive procedures for the purpose of diagnosis or staging of the disease are permitted.
• History of another malignancy in the last 5 years. Patients with prior history of in situ cancer, basal or squamous cell skin cancer are eligible. Patients with other malignancies are eligible if they were cured by surgery alone and have been continuously disease free for at least 5 years.
• Pregnant women are excluded from this study because irinotecan and paclitaxel are antineoplastic agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with agents used in this trial, breastfeeding should be discontinued if the mother is treated with these agents.
• Patients with known HIV, Hepatitis B, Hepatitis C or active Hepatitis A are excluded.
• Patients on any systemic steroids for any indication, with doses that have not been stabilized to the equivalent of \< 10 mg/day prednisone during the 30 days prior to study enrollment. This does not include short courses of steroids administered at high doses.
• Patients with the inability to absorb oral vorinostat.
• Patients with known allergy or hypersensitivity to any component of any of the study therapies.

Sponsors & Collaborators

• Milton S. Hershey Medical Center: lead
• Merck Sharp & Dohme LLC: collaborator
• University of Pennsylvania: collaborator

Study Sites (1)

Penn State College of Medicine, Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

MeSH Terms

Conditions

Small Cell Lung Carcinoma; Lung Neoplasms

Interventions

Vorinostat; Carboplatin; Etoposide

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Coordination Complexes; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Results Point of Contact

• Title: Dr. C. Belani
• Organization: MSHERSHEY MC

cbelani@psu.edu

717-531-1078

Study Officials

• Chandra P Belani, MD

  Penn State College of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: June 19, 2008
• First Posted: June 20, 2008
• Study Start: September 1, 2008
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: October 22, 2018
• Results First Posted: October 15, 2018

Record last verified: 2018-09

Locations

US (1)