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

Phase I portion: To determine MTD of Vorinostat when used in combination with other chemotherapy. Start at Vorinostat 200 mg PO QD D1-14; Carbo 6 (AUC) D3; Etoposide 100 mg/m2 D1,2,3; Vorinostat, Carboplatin, Etoposide, SAHA
Vorinostat, Carboplatin, Etoposide: Sequential cohorts of 3-6 patients will be entered to the following dose levels: Level 1 - Days 1-14: Vorinostat 200 mg po QD; Day 3: Carboplatin 6 AUC; Days 1,2,3: Etoposide 100 mg/m2. Level 2 - Days 1-14: Vorinostat 300 mg po QD; Day 3: Carboplatin 6 AUC; Days 1,2,3: Etoposide 100 mg/m2; Level 3: Days 1-14: Vorinostat 400 mg po QD; Day 3: Carboplatin 6 AUC; Days 1,2,3: Etoposide 100 mg/m2. Treatment cycles will be repeated every 3 weeks. A maximum of 4 cycles will be administered to each patient.

PHASE I: Vorinostat 200mg Carbo 6 (AUC)

Phase II portion: To determine progression free survival among patients with extensive disease SCLC receiving carboplatin plus etoposide with fixed dose Vorinostat. (Vorinostat, Carboplatin, Etoposide, SAHA)
SAHA: Once the recommended phase II dose has been established and additional 15 patients will be enrolled. Days 1-4 Vorinostat recommended phase II dose po QD;Day 3 Carboplatin 6 AUC; Days 1,2,3 Etoposide 100 mg/m2. Treatment cycles will be repeated every 3 weeks. A maximum of 4 cycles will be administered to each patient. An additional 35 patients on the phase II portion of the trial will be required to achieve the outlined objectives.

PHASE II: Vorinostat 300mg Carbo 6 (AUC)

Total

Sex: Female, Male

Region of Enrollment

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).

Vorinostat 200 mg PO QD D1-14; Carbo 6 (AUC) D3; Etoposide 100 mg/m2 D1,2,3 Vorinostat, Carboplatin, Etoposide, SAHA
Vorinostat, Carboplatin, Etoposide: Sequential cohorts of 3-6 patients will be entered to the following dose levels: Level 1 - Days 1-14: Vorinostat 200 mg po QD; Day 3: Carboplatin 6 AUC; Days 1,2,3: Etoposide 100 mg/m2. Level 2 - Days 1-14: Vorinostat 300 mg po QD; Day 3: Carboplatin 6 AUC; Days 1,2,3: Etoposide 100 mg/m2; Level 3: Days 1-14: Vorinostat 400 mg po QD; Day 3: Carboplatin 6 AUC; Days 1,2,3: Etoposide 100 mg/m2. Treatment cycles will be repeated every 3 weeks. A maximum of 4 cycles will be administered to each patient.

Phase I Dose Escalation of Vorinostat (200-400mg)

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

For the purpose of this study, overall survival is defined as the percentage of participants who are alive at two years post initiation of study treatment.

Participants with extensive disease SCLC receiving carboplatin, Etoposide, and a fixed dose (300mg) of vorinostat.
Days 1-4 Vorinostat 300mg po QD; Day 3 Carboplatin 6 AUC; Days 1,2,3 Etoposide 100 mg/m2. Treatment cycles will be repeated every 3 weeks. A maximum of 4 cycles will be administered to each participant.

Phase II Vorinostat 300mg With Carboplatin and Etoposide

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

Eligibility limits the study population to those who have measurable disease pre-treatment. This secondary outcome measure was intended to objectively evaluate disease response and survival rate in recipients of the investigational medication regimen. Disease response was performed using standard diagnostic imaging. Tumor markers and cytology may be used to support the imaging results. Objective response rate was defined as progression-free survival (PFS) among treatment recipients. PFS, is defined as time (in months) from entry to clinical evidence of disease progression or death without progression. The clinical trial closed prematurely due to low accrual. For this reason, an analysis of this secondary objective would not be meaningful. No analysis done.

Participants with extensive disease small cell lung cancer who receive carboplatin plus etoposide with a fixed dose of vorinostat. Participants will receive: Days 1-4 Vorinostat recommended phase II dose po QD; Day 3 Carboplatin 6 AUC; Days 1,2,3 Etoposide 100 mg/m2. Treatment cycles will be repeated every 3 weeks. A maximum of 4 cycles will be administered to each participant.

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

Evaluation of resultant adverse events that occurred with participants with extensive disease SCLC after initiating treatment using a fixed dose of vorinostat in combination with carboplatin and etoposide.

Participants with extensive disease SCLC receiving carboplatin, Etoposide, and a fixed dose (300mg) of vorinostat. Participants will receive on Days 1-4 Vorinostat 300mg po QD; Day 3 Carboplatin 6 AUC; Days 1,2,3 Etoposide 100 mg/m2. Treatment cycles will be repeated every 3 weeks. A maximum of 4 cycles will be administered to each participant.

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

Phase 2 is to determine progression free survival among patients with extensive disease SCLC receiving carboplatin plus etoposide with vorinostat.Vorinostat, Carboplatin, Etoposide, SAHA
SAHA: Once the recommended phase II dose has been established and additional 15 patients will be enrolled. Days 1-4 Vorinostat recommended phase II dose po QD;Day 3 Carboplatin 6 AUC; Days 1,2,3 Etoposide 100 mg/m2. Treatment cycles will be repeated every 3 weeks. A maximum of 4 cycles will be administered to each patient. An additional 35 patients on the phase II portion of the trial will be required to achieve the outlined objectives.

Phase II Portion - Vorinostat 300mg

Vorinostat 200 mg PO QD D1-14; Carbo 6 (AUC) D3; Etoposide 100 mg/m2 D1,2,3 Vorinostat, Carboplatin, Etoposide, SAHA.
Vorinostat, Carboplatin, Etoposide: Sequential cohorts of 3-6 patients will be entered to the following dose levels: Level 1 - Days 1-14: Vorinostat 200 mg po QD; Day 3: Carboplatin 6 AUC; Days 1,2,3: Etoposide 100 mg/m2. Level 2 - Days 1-14: Vorinostat 300 mg po QD; Day 3: Carboplatin 6 AUC; Days 1,2,3: Etoposide 100 mg/m2; Level 3: Days 1-14: Vorinostat 400 mg po QD; Day 3: Carboplatin 6 AUC; Days 1,2,3: Etoposide 100 mg/m2. Treatment cycles will be repeated every 3 weeks. A maximum of 4 cycles will be administered to each patient. Phase I was prematurely closed as an NCI study established the MTD. This study proceeded to Phase II soon after the first participant was enrolled at Dose Level 2 (300mg).

Phase I Portion - Vorinostat 200mg

Overall Study

Dr. C. Belani

Phase 2 objective is to determine progression free survival among patients with extensive disease SCLC receiving carboplatin plus etoposide using an established dose of Vorinostat.
Participants in Phase II received a "cycle" consisting of the NCI recommended Vorinostat dose with Carboplatin 6 AUC and Etoposide 100 mg/m2. Treatment cycles were repeated every 3 weeks. A maximum of 4 cycles were administered. A total of 35 participants were required for Phase II analysis. The Phase II study closed prematurely due to low accrual. Analysis of the primary and secondary objectives was not possible due to inadequate sample size.

Phase II: Vorinostat 300mg With Carboplatin and Etoposide

The original purpose of the Phase I portion was to establish the MTD of Vorinostat when provided with other chemotherapy (Carboplatin and Etoposide). Initial dose at 200mg, then 300, to a max of 400 mg. The first cohort at 200 mg did well with no dose limiting toxicities. After the enrollment of the 1st participant into cohort 2, the Phase I study was prematurely closed as concurrent NCI publications had established appropriate dose levels. The phase I portion was closed after the first 3 participants. Analysis of the objectives is not applicable due to premature closing.

Phase I: Determine MTD Vorinostat (200mg-400mg)

Small Cell Lung Cancer

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.

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

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