Neoplasms
Conditions
Keywords
Non-Small Cell Lung Cancer (NSCLC)
Brief summary
The clinical study will evaluate safety, tolerability and Pharmacokinetics of MK0683 in combination with carboplatin and paclitaxel in chemotherapy-naive NSCLC patients.
Interventions
DRUGMK0683, vorinostat
vorinostat 300 mg or 400 mg once daily consecutive days (14 days) followed by 11 days of rest in the first cycle or 7 days of rest in the second or later cycle.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Chemotherapy-naive patients who are histologically or cytologically diagnosed NSCLC with stage IIIB (not applicable of radical thoracic radiation) or stage IV * Patients with normal organ function and bone marrow function
Exclusion criteria
* Given radical thoracic radiation for NSCLC or radiation for other than original lesion within 3 weeks * Any peripheral neuropathy above grade 2 * Any ascites, pleural effusion or pericardiac effusion which requires treatment * Any uncontrolled concomitant illness * Pregnant or breast-feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Dose Limited Toxicity at First Cycle | 25 Days (first cycle) | Dose Limited Toxicity = Drug-related side effects that are serious enough to prevent an increase in dose or level of that treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve (AUC(0-24 hr)) at Day 4 | Day 4 | Area Under the Curve (AUC (0-24 hr)) = Area under the plasma concentration versus time curve (AUC) from time zero to 24 hour. |
| Area Under the Curve (AUC(0-24 hr)) at Day 5 | Day 5 | Area Under the Curve (AUC (0-24 hr)) = Area under the plasma concentration versus time curve (AUC) from time zero to 24 hour. |
| Maximum Concentration (Cmax) at Day 4 | Day 4 | Maximum Concentration (Cmax) = the maximum plasma concentration of the drug |
| Maximum Concentration (Cmax) at Day 5 | Day 5 | Maximum Concentration (Cmax) = the maximum plasma concentration of the drug |
Participant flow
Recruitment details
Date of first participant in: 26 January 2007. Data of last participant's last visit in study protocol: 7 March 2007. The study was conducted at single center in Japan.
Pre-assignment details
Vorinostat with Carboplatin and Paclitaxel were investigated in participants with chemotherapy-naive non-small cell lung cancer. Enroll 3 participants to dose level 1 of vorinostat and decide whether to enroll additional participants based on the Dose Limited Toxicity (DLT) manifestation. The starting dose of vorinostat was 300 mg once daily.
Participants by arm
| Arm | Count |
|---|---|
| Vorinostat (300 mg) This group includes data from all participants who were treated with vorinostat 300 mg once daily consecutive days (14 days) followed by 11 days of rest (first cycle). | 3 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Lack of Efficacy | 1 | 0 |
Baseline characteristics
| Characteristic | Vorinostat (300 mg) |
|---|---|
| Age, Continuous | 64 years STANDARD_DEVIATION 2 |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 3 / — |
| serious Total, serious adverse events | 0 / 3 |
Outcome results
Primary
Number of Participants With a Dose Limited Toxicity at First Cycle
Dose Limited Toxicity = Drug-related side effects that are serious enough to prevent an increase in dose or level of that treatment.
Time frame: 25 Days (first cycle)
Population: All participants who received vorinostat 300 mg once daily.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vorinostat (300 mg) | Number of Participants With a Dose Limited Toxicity at First Cycle | 3 Participants |
Secondary
Area Under the Curve (AUC(0-24 hr)) at Day 4
Area Under the Curve (AUC (0-24 hr)) = Area under the plasma concentration versus time curve (AUC) from time zero to 24 hour.
Time frame: Day 4
Population: Participants who received vorinostat 300 mg once daily and had Pharmacokinetics Data on Day 4.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Vorinostat (300 mg) | Area Under the Curve (AUC(0-24 hr)) at Day 4 | 9.76 µM hr |
Secondary
Area Under the Curve (AUC(0-24 hr)) at Day 5
Area Under the Curve (AUC (0-24 hr)) = Area under the plasma concentration versus time curve (AUC) from time zero to 24 hour.
Time frame: Day 5
Population: Participants who received vorinostat 300 mg once daily and had Pharmacokinetics Data on Day 5.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Vorinostat (300 mg) | Area Under the Curve (AUC(0-24 hr)) at Day 5 | 6.26 µM hr |
Secondary
Maximum Concentration (Cmax) at Day 4
Maximum Concentration (Cmax) = the maximum plasma concentration of the drug
Time frame: Day 4
Population: Participants who received vorinostat 300 mg once daily and had Pharmacokinetics Data on Day 4.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Vorinostat (300 mg) | Maximum Concentration (Cmax) at Day 4 | 1.54 µM |
Secondary
Maximum Concentration (Cmax) at Day 5
Maximum Concentration (Cmax) = the maximum plasma concentration of the drug
Time frame: Day 5
Population: Participants who received vorinostat 300 mg once daily and had Pharmacokinetics Data on Day 5.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Vorinostat (300 mg) | Maximum Concentration (Cmax) at Day 5 | 1.96 µM |