Trial Outcomes & Findings for Phase I Imaging Study Evaluating Gem/Cis or Gem/Carbo for Participants With Non-Small Cell Lung Cancer (MK-0000-083 AM3) (NCT NCT00599755)

Last Updated: 2018-01-16

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

68 participants

Primary outcome timeframe

Weeks 3 and 6 following chemotherapy

Results posted on

2018-01-16

Participant Flow

Participant milestones

Participant milestones
Measure	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
Overall Study STARTED	68
Overall Study COMPLETED	49
Overall Study NOT COMPLETED	19

Reasons for withdrawal

Reasons for withdrawal
Measure	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
Overall Study Adverse Event	11
Overall Study Withdrawal by Subject	2
Overall Study Progression of Disease	3
Overall Study Other Reason	2
Overall Study No data available	1

Baseline Characteristics

Phase I Imaging Study Evaluating Gem/Cis or Gem/Carbo for Participants With Non-Small Cell Lung Cancer (MK-0000-083 AM3)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Gemcitabine and Cisplatin or Gemcitabine and Carboplatin n=68 Participants Tumor uptake of FDG is imaged by PET both before and after combination chemotherapy with Gem/Cis or Gem/Carbo
Age, Continuous	62.9 years STANDARD_DEVIATION 8.6 • n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants
Sex: Female, Male Male	49 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Gemcitabine and Cisplatin or Gemcitabine and Carboplatin n=25 Participants Tumor uptake of FDG is imaged by PET both before and after combination chemotherapy with Gem/Cis or Gem/Carbo
Metabolic Response Conversion Rate Between 3 and 6 Weeks After Starting Chemotherapy at a Threshold of a 20% Decrease in SUVmean	10 Participants

SECONDARY outcome

Timeframe: Between -14 to -6 days and between -5 to 0 days prior to starting chemotherapy

Population: Participants who underwent two baseline PET scans

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.

Outcome measures

Outcome measures
Measure	Gemcitabine and Cisplatin or Gemcitabine and Carboplatin n=64 Participants Tumor uptake of FDG is imaged by PET both before and after combination chemotherapy with Gem/Cis or Gem/Carbo
Repeatability of FDG SUVmean at Baseline	3.79 SUVmean Standard Deviation 1.14

SECONDARY outcome

Timeframe: Baseline and Week 3

Population: Participants with PET scans at baseline and 3 weeks after starting chemotherapy

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.

Outcome measures

Outcome measures
Measure	Gemcitabine and Cisplatin or Gemcitabine and Carboplatin n=54 Participants Tumor uptake of FDG is imaged by PET both before and after combination chemotherapy with Gem/Cis or Gem/Carbo
Change in FDG-PET Uptake From Baseline to Week 3	0.75 Fold Change in SUVmean Interval 0.7 to 0.8

SECONDARY outcome

Timeframe: Week 3 and Week 6

Population: Participants with PET scans at 3 weeks and 6 weeks after starting chemotherapy

Outcome measures

Outcome measures
Measure	Gemcitabine and Cisplatin or Gemcitabine and Carboplatin n=47 Participants Tumor uptake of FDG is imaged by PET both before and after combination chemotherapy with Gem/Cis or Gem/Carbo
Change in FDG-PET Uptake From Week 3 to Week 6	0.85 Fold change in SUVmean Interval 0.81 to 0.9

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: Participants with PET scans at baseline and 6 weeks after starting chemotherapy.

Outcome measures

Outcome measures
Measure	Gemcitabine and Cisplatin or Gemcitabine and Carboplatin n=47 Participants Tumor uptake of FDG is imaged by PET both before and after combination chemotherapy with Gem/Cis or Gem/Carbo
Change in FGD-PET Uptake From Baseline to Week 6	0.65 Fold change in SUVmean Interval 0.6 to 0.71

POST_HOC outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	Gemcitabine and Cisplatin or Gemcitabine and Carboplatin n=32 Participants Tumor uptake of FDG is imaged by PET both before and after combination chemotherapy with Gem/Cis or Gem/Carbo
Metabolic Response Conversion Rate Between 3 and 6 Weeks After Starting Chemotherapy At a Threshold of a 30% Decrease in SUVmean	4 Participants

Adverse Events

Gemcitabine and Cisplatin or Gemcitabine and Carboplatin

Serious events: 24 serious events

Other events: 61 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Gemcitabine and Cisplatin or Gemcitabine and Carboplatin n=68 participants at risk Tumor uptake of FDG is imaged by PET both before and after combination chemotherapy with Gem/Cis or Gem/Carbo
Blood and lymphatic system disorders Anaemia	1.5% 1/68 • Number of events 1
Blood and lymphatic system disorders Neutropenia	1.5% 1/68 • Number of events 1
Blood and lymphatic system disorders Pancytopenia	1.5% 1/68 • Number of events 1
Blood and lymphatic system disorders Thrombocytopenia	1.5% 1/68 • Number of events 1
Cardiac disorders Angina pectoris	1.5% 1/68 • Number of events 1
Cardiac disorders Atrial fibrillation	2.9% 2/68 • Number of events 2
Cardiac disorders Cardiac failure congestive	1.5% 1/68 • Number of events 1
Cardiac disorders Cardiac valve disease	1.5% 1/68 • Number of events 1
Cardiac disorders Myocardial infarction	1.5% 1/68 • Number of events 1
Gastrointestinal disorders Dysphagia	1.5% 1/68 • Number of events 1
Gastrointestinal disorders Pancreatitis acute	1.5% 1/68 • Number of events 1
General disorders Disease progression	1.5% 1/68 • Number of events 1
General disorders Non-cardiac chest pain	1.5% 1/68 • Number of events 1
General disorders Pyrexia	1.5% 1/68 • Number of events 1
Infections and infestations Influenza	1.5% 1/68 • Number of events 1
Infections and infestations Lobar pneumonia	1.5% 1/68 • Number of events 1
Infections and infestations Lower respiratory tract infection	2.9% 2/68 • Number of events 2
Infections and infestations Lung abscess	1.5% 1/68 • Number of events 1
Infections and infestations Neutropenic sepsis	1.5% 1/68 • Number of events 1
Infections and infestations Pneumonia	4.4% 3/68 • Number of events 3
Metabolism and nutrition disorders Hyperglycemia	1.5% 1/68 • Number of events 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	1.5% 1/68 • Number of events 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm malignant	2.9% 2/68 • Number of events 2
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour associated fever	1.5% 1/68 • Number of events 1
Nervous system disorders VIIth nerve paralysis	1.5% 1/68 • Number of events 1
Respiratory, thoracic and mediastinal disorders Mediastinal mass	1.5% 1/68 • Number of events 1
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.5% 1/68 • Number of events 1
Skin and subcutaneous tissue disorders Hyperhidrosis	1.5% 1/68 • Number of events 1
Vascular disorders Aortic aneurysm rupture	1.5% 1/68 • Number of events 1
Vascular disorders Superior vena cava syndrome	1.5% 1/68 • Number of events 1

Other adverse events

Other adverse events
Measure	Gemcitabine and Cisplatin or Gemcitabine and Carboplatin n=68 participants at risk Tumor uptake of FDG is imaged by PET both before and after combination chemotherapy with Gem/Cis or Gem/Carbo
Blood and lymphatic system disorders Anaemia	5.9% 4/68 • Number of events 4
Blood and lymphatic system disorders Neutropenia	16.2% 11/68 • Number of events 12
Gastrointestinal disorders Constipation	17.6% 12/68 • Number of events 12
Gastrointestinal disorders Diarrhoea	8.8% 6/68 • Number of events 6
Gastrointestinal disorders Nausea	41.2% 28/68 • Number of events 29
Gastrointestinal disorders Vomiting	14.7% 10/68 • Number of events 10
General disorders Asthenia	10.3% 7/68 • Number of events 7
General disorders Chest pain	7.4% 5/68 • Number of events 5
General disorders Fatigue	20.6% 14/68 • Number of events 14
General disorders Pyrexia	11.8% 8/68 • Number of events 8
Investigations Neutrophil count decreased	8.8% 6/68 • Number of events 7
Metabolism and nutrition disorders Decreased appetite	25.0% 17/68 • Number of events 17
Metabolism and nutrition disorders Hypokalemia	5.9% 4/68 • Number of events 4
Musculoskeletal and connective tissue disorders Back pain	7.4% 5/68 • Number of events 5
Nervous system disorders Dizziness	7.4% 5/68 • Number of events 6
Psychiatric disorders Insomnia	5.9% 4/68 • Number of events 4
Respiratory, thoracic and mediastinal disorders Cough	7.4% 5/68 • Number of events 5
Respiratory, thoracic and mediastinal disorders Dyspnoea	14.7% 10/68 • Number of events 10
Respiratory, thoracic and mediastinal disorders Hiccups	5.9% 4/68 • Number of events 4
Skin and subcutaneous tissue disorders Alopecia	8.8% 6/68 • Number of events 6
Skin and subcutaneous tissue disorders Pruritus	5.9% 4/68 • Number of events 4
Skin and subcutaneous tissue disorders Rash	10.3% 7/68 • Number of events 8

Additional Information

Senior Vice President,Global Clinical Development

Merck Sharp and Dohme Corp

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Subsequent to multicenter publication, or 24 months after study completion, whichever comes first, an investigator and/or colleague(s) may publish the results for their study site independently. The SPONSOR recommends against this practice due to scientific concerns. The SPONSOR must have the opportunity to review all publications or presentations regarding this study 60 days prior to submission, and any information identified by the SPONSOR as confidential must be deleted prior to submission.
Publication restrictions are in place

Restriction type: OTHER