Non-Small Cell Lung Cancer
Conditions
Keywords
Advanced Stage IIIB/IV Non-Small Cell Lung Cancer
Brief summary
This is a clinical trial to determine the safety and tolerability of MK0683 in combination with gemcitabine and cisplatin and/or carboplatin.
Interventions
DRUGvorinostat
Dose escalation study: vorinostat 300-500 mg capsules once daily for 7-14 days in continuous cycles of 21 days
DRUGGemcitabine
Dose escalation study: Gemcitabine 1000-1250 mg/m2 will be given for 2 days in each 21 day cycle
DRUGPlatinum-based agent
Cisplatin IV 75 mg/m2 will be given for 1 day in each 21 day cycle or carboplatin dosed according to renal function.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient must have a histologically-confirmed metastatic or locally advanced non-small cell lung cancer that has not been previously treated with systemic chemotherapy or has received non-platinum and non-gemcitabine based neoadjuvant or adjuvant chemotherapy if the last dose was at least 6 months prior to study enrollment
Exclusion criteria
* Patient who has had chemotherapy, radiotherapy, or biological therapy prior to entering the study, except for adjuvant or neoadjuvant chemotherapy, as allowed for treatment of a tumor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose-limiting Toxicities (DLT) Due to Vorinostat Administered in Combination With Standard Dose of Gemcitabine Plus Either Cisplatin or Carboplatin | every 21 days (every cycle), up to 126 days (6 cycles) | DLT = any Common Terminology Criteria for Adverse Events Grade 3/4 drug related non-hematologic toxicity EXCEPT Grade 3 nausea/vomiting responsive to therapy, Grade 3 Fatigue responsive to management, transient electrolyte disorders that were corrected, any Grade 4 drug related hematologic toxicity EXCEPT lymphopenia/neutropenia, unless the neutropenia was febrile and/or was an infection requiring treatment, OR Any Grade 4 neutropenia lasting \>=7 days, failure of absolute neutrophil count or platelets to recover, or any drug-related AE that led to a dose reduction of \>=1 study drugs. |
| Maximum Tolerated Dose of Vorinostat Administered in Combination With Standard Doses of Gemcitabine Plus Either Cisplatin or Carboplatin in Patients With Advanced Stage Non-Small Cell Lung Cancer Who Have Not Received Chemotherapy for Advanced Disease | every 21 days (every cycle), up to 126 days (6 cycles) | Maximum tolerated dose (MTD) was defined as the highest dose level in which fewer than 2 patients among the first 6 enrolled experience a DLT (as defined in Outcome Measure 1) during the first cycle of treatment. The MTD was 400 mg for up to 10 days in 21-day cycles. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinical Adverse Experiences (Safety and Tolerability) | every 21 days (every cycle), up to 126 days (6 cycles) | An adverse experience (AE) was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the sponsor's product, whether or not considered related to the use of the product. Any worsening (any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the sponsor's product, was also an adverse experience. The AEs could have been any grade from 1 to 5 in severity (mild, moderate, severe, life-threatening, death, respectively). |
| Number of Participants With Laboratory Adverse Experiences (Safety and Tolerability) | every 21 days (every cycle), up to 126 days (6 cycles) | An adverse experience was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the sponsor's product, whether or not considered related to the use of the product. Any worsening (any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the sponsor's product, was also an adverse experience. The AEs could have been any grade from 1 to 5 in severity (mild, moderate, severe, life-threatening, death, respectively). |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants Vorinostat + Gemcitabine + Cisplatin | 61 |
| Total | 61 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Clinical Adverse Event | 1 | 0 | 1 | 8 | 2 |
| Overall Study | Death | 1 | 0 | 2 | 1 | 1 |
| Overall Study | Laboratory Adverse Event | 0 | 1 | 2 | 0 | 0 |
| Overall Study | Other | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Progressive Disease | 1 | 3 | 8 | 11 | 4 |
| Overall Study | Protocol Violation | 0 | 0 | 2 | 1 | 0 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 56.7 years STANDARD_DEVIATION 9.2 |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 4 | 6 / 6 | 17 / 18 | 27 / 27 | 7 / 7 |
| serious Total, serious adverse events | 3 / 4 | 4 / 6 | 10 / 18 | 18 / 27 | 4 / 7 |
Outcome results
Primary
Maximum Tolerated Dose of Vorinostat Administered in Combination With Standard Doses of Gemcitabine Plus Either Cisplatin or Carboplatin in Patients With Advanced Stage Non-Small Cell Lung Cancer Who Have Not Received Chemotherapy for Advanced Disease
Maximum tolerated dose (MTD) was defined as the highest dose level in which fewer than 2 patients among the first 6 enrolled experience a DLT (as defined in Outcome Measure 1) during the first cycle of treatment. The MTD was 400 mg for up to 10 days in 21-day cycles.
Time frame: every 21 days (every cycle), up to 126 days (6 cycles)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vorinostat 300 7/21+ Gemcitabine 1000 + Cisplatin | Maximum Tolerated Dose of Vorinostat Administered in Combination With Standard Doses of Gemcitabine Plus Either Cisplatin or Carboplatin in Patients With Advanced Stage Non-Small Cell Lung Cancer Who Have Not Received Chemotherapy for Advanced Disease | 400 mg |
Primary
Number of Participants With Dose-limiting Toxicities (DLT) Due to Vorinostat Administered in Combination With Standard Dose of Gemcitabine Plus Either Cisplatin or Carboplatin
DLT = any Common Terminology Criteria for Adverse Events Grade 3/4 drug related non-hematologic toxicity EXCEPT Grade 3 nausea/vomiting responsive to therapy, Grade 3 Fatigue responsive to management, transient electrolyte disorders that were corrected, any Grade 4 drug related hematologic toxicity EXCEPT lymphopenia/neutropenia, unless the neutropenia was febrile and/or was an infection requiring treatment, OR Any Grade 4 neutropenia lasting \>=7 days, failure of absolute neutrophil count or platelets to recover, or any drug-related AE that led to a dose reduction of \>=1 study drugs.
Time frame: every 21 days (every cycle), up to 126 days (6 cycles)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vorinostat 300 7/21+ Gemcitabine 1000 + Cisplatin | Number of Participants With Dose-limiting Toxicities (DLT) Due to Vorinostat Administered in Combination With Standard Dose of Gemcitabine Plus Either Cisplatin or Carboplatin | 0 Participants |
| Vorinostat 300 7/21+ Gemcitabine 1250 + Cisplatin | Number of Participants With Dose-limiting Toxicities (DLT) Due to Vorinostat Administered in Combination With Standard Dose of Gemcitabine Plus Either Cisplatin or Carboplatin | 1 Participants |
| Vorinostat 400 7/21+ Gemcitabine 1250 + Cisplatin | Number of Participants With Dose-limiting Toxicities (DLT) Due to Vorinostat Administered in Combination With Standard Dose of Gemcitabine Plus Either Cisplatin or Carboplatin | 0 Participants |
| Vorinostat 400 10/21+ Gemcitabine 1250 + Cisplatin | Number of Participants With Dose-limiting Toxicities (DLT) Due to Vorinostat Administered in Combination With Standard Dose of Gemcitabine Plus Either Cisplatin or Carboplatin | 0 Participants |
| Vorinostat 400 14/21+ Gemcitabine 1250 + Cisplatin | Number of Participants With Dose-limiting Toxicities (DLT) Due to Vorinostat Administered in Combination With Standard Dose of Gemcitabine Plus Either Cisplatin or Carboplatin | 1 Participants |
Secondary
Number of Participants With Clinical Adverse Experiences (Safety and Tolerability)
An adverse experience (AE) was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the sponsor's product, whether or not considered related to the use of the product. Any worsening (any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the sponsor's product, was also an adverse experience. The AEs could have been any grade from 1 to 5 in severity (mild, moderate, severe, life-threatening, death, respectively).
Time frame: every 21 days (every cycle), up to 126 days (6 cycles)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vorinostat 300 7/21+ Gemcitabine 1000 + Cisplatin | Number of Participants With Clinical Adverse Experiences (Safety and Tolerability) | 4 Participants |
| Vorinostat 300 7/21+ Gemcitabine 1250 + Cisplatin | Number of Participants With Clinical Adverse Experiences (Safety and Tolerability) | 6 Participants |
| Vorinostat 400 7/21+ Gemcitabine 1250 + Cisplatin | Number of Participants With Clinical Adverse Experiences (Safety and Tolerability) | 17 Participants |
| Vorinostat 400 10/21+ Gemcitabine 1250 + Cisplatin | Number of Participants With Clinical Adverse Experiences (Safety and Tolerability) | 27 Participants |
| Vorinostat 400 14/21+ Gemcitabine 1250 + Cisplatin | Number of Participants With Clinical Adverse Experiences (Safety and Tolerability) | 7 Participants |
Secondary
Number of Participants With Laboratory Adverse Experiences (Safety and Tolerability)
An adverse experience was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the sponsor's product, whether or not considered related to the use of the product. Any worsening (any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the sponsor's product, was also an adverse experience. The AEs could have been any grade from 1 to 5 in severity (mild, moderate, severe, life-threatening, death, respectively).
Time frame: every 21 days (every cycle), up to 126 days (6 cycles)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vorinostat 300 7/21+ Gemcitabine 1000 + Cisplatin | Number of Participants With Laboratory Adverse Experiences (Safety and Tolerability) | 2 Participants |
| Vorinostat 300 7/21+ Gemcitabine 1250 + Cisplatin | Number of Participants With Laboratory Adverse Experiences (Safety and Tolerability) | 4 Participants |
| Vorinostat 400 7/21+ Gemcitabine 1250 + Cisplatin | Number of Participants With Laboratory Adverse Experiences (Safety and Tolerability) | 7 Participants |
| Vorinostat 400 10/21+ Gemcitabine 1250 + Cisplatin | Number of Participants With Laboratory Adverse Experiences (Safety and Tolerability) | 13 Participants |
| Vorinostat 400 14/21+ Gemcitabine 1250 + Cisplatin | Number of Participants With Laboratory Adverse Experiences (Safety and Tolerability) | 2 Participants |