Carcinoma, Non-small Cell Lung Cancer
Conditions
Brief summary
This study will use imaging to look at tumor response to combination chemotherapy of gemcitabine (Gem) and cisplatin (Cis) or gemcitabine and carboplatin (Carbo) in non small cell lung cancer (NSCLC).
Interventions
RADIATIONComparator: CT or MRI and FDG-PET
Participants have 4 computed tomography (CT) or magnetic resonance imaging (MRI) scans at screening, baseline, at the end of each treatment cycle (day 21 and day 42.) They also have FDG-PET scans, 2 at Baseline and one at the end of each treatment cycle.
DRUGGemcitabine and Cisplatin or Gemcitabine and Carboplatin
Gemcitabine administered intravenously at a dose of 1000-1250 mg/m\^2 on Day 1 and Day 8 of each cycle; Cisplatin administered intravenously at a dose of 60-85 mg/m\^2 or Carboplatin at a dose of 4-6 Area Under the Curve (AUC) on Day 1 of each cycle. Two cycles are given 3 weeks apart.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has histologically or cytopathologically confirmed metastatic or locally advanced stage IIIB/IV Non-small cell lung cancer (NSCLC) * Has measurable disease * Has not been previously treated with surgery (involving the thorax), radiation (unless it was for a metastatic site), or chemotherapy for NSCLC * Is 18 years of age or older * Has a performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) scale * Women of childbearing potential have a negative pregnancy test
Exclusion criteria
* Is participating in or has participated in a study with an investigational compound or device within 30 days or 5 half-lives of the start of treatment * Has untreated brain metastases related to their NSCLC or carcinomatous meningitis * Abuses drugs or alcohol * Is pregnant or breastfeeding * Is Human Immunodeficiency Virus (HIV) positive * Has active viral hepatitis * Has hearing loss * Has poorly controlled diabetes mellitus * Is allergic to gemcitabine, cisplatin or carboplatin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Metabolic Response Conversion Rate Between 3 and 6 Weeks After Starting Chemotherapy at a Threshold of a 20% Decrease in SUVmean | Weeks 3 and 6 following chemotherapy | Metabolic response conversion rate is the number of participants initially classified as non-metabolic responders relative to baseline at week 3 after starting chemotherapy, who are then, relative to week 3, reclassified as metabolic responders at week 6 after starting chemotherapy, based on a pre-specified threshold of a 20% decrease in mean standardized uptake value (SUVmean) of \[18F\]-Fluorodeoxyglucose (FDG). The SUVmean was calculated by summing the radioactivity from volumes of interest within each tumor and normalizing for the injected dose and lean body mass. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Repeatability of FDG SUVmean at Baseline | Between -14 to -6 days and between -5 to 0 days prior to starting chemotherapy | Two positron emission tomography (PET) scans are obtained on different days at baseline, as close together as possible, under conditions of no biological change, to measure FDG SUVmean. The SUVmean was calculated by summing the radioactivity from volumes of interest within each tumor and normalizing for the injected dose and lean body mass. |
| Change in FDG-PET Uptake From Baseline to Week 3 | Baseline and Week 3 | Fold change in SUVmean of FDG uptake with accompanying 80% Confidence Interval. The SUVmean was calculated by summing the radioactivity from volumes of interest within each tumor and normalizing for the injected dose and lean body mass. |
| Change in FDG-PET Uptake From Week 3 to Week 6 | Week 3 and Week 6 | Fold change in SUVmean of FDG uptake with accompanying 80% Confidence Interval. The SUVmean was calculated by summing the radioactivity from volumes of interest within each tumor and normalizing for the injected dose and lean body mass. |
| Change in FGD-PET Uptake From Baseline to Week 6 | Baseline and Week 6 | Fold change in SUVmean of FDG uptake with accompanying 80% Confidence Interval. The SUVmean was calculated by summing the radioactivity from volumes of interest within each tumor and normalizing for the injected dose and lean body mass. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Gemcitabine and Cisplatin or Gemcitabine and Carboplatin Tumor uptake of FDG is imaged by PET both before and after combination chemotherapy with Gem/Cis or Gem/Carbo | 68 |
| Total | 68 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 11 |
| Overall Study | No data available | 1 |
| Overall Study | Other Reason | 2 |
| Overall Study | Progression of Disease | 3 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Gemcitabine and Cisplatin or Gemcitabine and Carboplatin |
|---|---|
| Age, Continuous | 62.9 years STANDARD_DEVIATION 8.6 |
| Sex: Female, Male Female | 19 Participants |
| Sex: Female, Male Male | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 61 / 68 |
| serious Total, serious adverse events | 24 / 68 |
Outcome results
Primary
Metabolic Response Conversion Rate Between 3 and 6 Weeks After Starting Chemotherapy at a Threshold of a 20% Decrease in SUVmean
Metabolic response conversion rate is the number of participants initially classified as non-metabolic responders relative to baseline at week 3 after starting chemotherapy, who are then, relative to week 3, reclassified as metabolic responders at week 6 after starting chemotherapy, based on a pre-specified threshold of a 20% decrease in mean standardized uptake value (SUVmean) of \[18F\]-Fluorodeoxyglucose (FDG). The SUVmean was calculated by summing the radioactivity from volumes of interest within each tumor and normalizing for the injected dose and lean body mass.
Time frame: Weeks 3 and 6 following chemotherapy
Population: Participants with evaluable scans classified as non-metabolic responders relative to baseline at 3 Weeks after starting chemotherapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gemcitabine and Cisplatin or Gemcitabine and Carboplatin | Metabolic Response Conversion Rate Between 3 and 6 Weeks After Starting Chemotherapy at a Threshold of a 20% Decrease in SUVmean | 10 Participants |
80% CI: [0.27, 0.55]
Secondary
Change in FDG-PET Uptake From Baseline to Week 3
Fold change in SUVmean of FDG uptake with accompanying 80% Confidence Interval. The SUVmean was calculated by summing the radioactivity from volumes of interest within each tumor and normalizing for the injected dose and lean body mass.
Time frame: Baseline and Week 3
Population: Participants with PET scans at baseline and 3 weeks after starting chemotherapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gemcitabine and Cisplatin or Gemcitabine and Carboplatin | Change in FDG-PET Uptake From Baseline to Week 3 | 0.75 Fold Change in SUVmean |
Secondary
Change in FDG-PET Uptake From Week 3 to Week 6
Fold change in SUVmean of FDG uptake with accompanying 80% Confidence Interval. The SUVmean was calculated by summing the radioactivity from volumes of interest within each tumor and normalizing for the injected dose and lean body mass.
Time frame: Week 3 and Week 6
Population: Participants with PET scans at 3 weeks and 6 weeks after starting chemotherapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gemcitabine and Cisplatin or Gemcitabine and Carboplatin | Change in FDG-PET Uptake From Week 3 to Week 6 | 0.85 Fold change in SUVmean |
Secondary
Change in FGD-PET Uptake From Baseline to Week 6
Fold change in SUVmean of FDG uptake with accompanying 80% Confidence Interval. The SUVmean was calculated by summing the radioactivity from volumes of interest within each tumor and normalizing for the injected dose and lean body mass.
Time frame: Baseline and Week 6
Population: Participants with PET scans at baseline and 6 weeks after starting chemotherapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gemcitabine and Cisplatin or Gemcitabine and Carboplatin | Change in FGD-PET Uptake From Baseline to Week 6 | 0.65 Fold change in SUVmean |
Secondary
Repeatability of FDG SUVmean at Baseline
Two positron emission tomography (PET) scans are obtained on different days at baseline, as close together as possible, under conditions of no biological change, to measure FDG SUVmean. The SUVmean was calculated by summing the radioactivity from volumes of interest within each tumor and normalizing for the injected dose and lean body mass.
Time frame: Between -14 to -6 days and between -5 to 0 days prior to starting chemotherapy
Population: Participants who underwent two baseline PET scans
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Gemcitabine and Cisplatin or Gemcitabine and Carboplatin | Repeatability of FDG SUVmean at Baseline | 3.79 SUVmean | Standard Deviation 1.14 |
80% CI: [0.85, 0.92]
Post Hoc
Metabolic Response Conversion Rate Between 3 and 6 Weeks After Starting Chemotherapy At a Threshold of a 30% Decrease in SUVmean
Metabolic response conversion rate is the number of participants initially classified as non-metabolic responders relative to baseline at week 3 after starting chemotherapy, who are then, relative to week 3, reclassified as metabolic responders at week 6 after starting chemotherapy, based on a pre-specified threshold of a 30% decrease in SUVmean of \[18F\]-Fluorodeoxyglucose (FDG). The SUVmean was calculated by summing the radioactivity from volumes of interest within each tumor and normalizing for the injected dose and lean body mass.
Time frame: Weeks 3 and 6 following chemotherapy
Population: Participants with evaluable scans classified as non-metabolic responders relative to baseline at 3 Weeks after starting chemotherapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gemcitabine and Cisplatin or Gemcitabine and Carboplatin | Metabolic Response Conversion Rate Between 3 and 6 Weeks After Starting Chemotherapy At a Threshold of a 30% Decrease in SUVmean | 4 Participants |
80% CI: [0.06, 0.23]