Trial Outcomes & Findings for The 'MADe IT' Clinical Trial: Molecular Analyses Directed Individualized Therapy for Advanced Non-Small Cell Lung Cancer (NCT NCT00215930)

Last Updated: 2017-03-23

Results Overview

Determine the number of participants for each category of response rates (RR) in newly diagnosed patients with advanced non-small cell lung cancer (NSCLC) who are treated with a chemotherapeutic regimen assigned to them on the basis of expression of the genes ribonucleotide reductase subunit 1 (ERCC1) and excision repair cross-complementing group 1 gene (RRM1) expression. Prior to treatment we measured the level of ERCC1 and RRM1 expression in the patients tumor, on the basis of which the patient would be assigned a specific doublet chemotherapy.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

53 participants

Primary outcome timeframe

24 Months

Results posted on

2017-03-23

Participant Flow

Assignments: High ERCC1 expression and High RRM1 Expression - vinorelbine plus docetaxel (DV); High ERCC1 expression but NOT High RRM1 expression - docetaxel plus gemcitabine (GD); High ERCC1 expression, but HAVE High RRM1 - carboplatin plus docetaxel (DC); High ERCC1 expression and do NOT have High RRM1 - carboplatin plus gemcitabine (GC)

Participant milestones

Participant milestones
Measure	Double Agent Chemotherapy Molecular Analysis-Directed Chemotherapy Assignment based on gene expression of Ribonucleotide reductase subunit 1(ERCC1) and Excision repair cross-complementing group 1 gene (RRM1). GD group was treated with gemcitabine (1,250 mg/m2 on days 1 and 8) and docetaxel (40 mg/m2 on days 1 and 8) every 21 days. DC group was treated with docetaxel (75 mg/m2 on day 1) and carboplatin (AUC 5 on day 1) every 21 days. DV group was treated with vinorelbine (45mg/m2ondays 1 and 15) and docetaxel (60mg/m2ondays 1 and 15) every 28 days. GC group was treated with gemcitabine (1,250 mg/m2 on days 1 and 8) and carboplatin (area under the concentration-time curve \[AUC\] of 5 on day 1) every 21 days.
Overall Study STARTED	53
Overall Study COMPLETED	53
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

The 'MADe IT' Clinical Trial: Molecular Analyses Directed Individualized Therapy for Advanced Non-Small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Double Agent Chemotherapy n=53 Participants Molecular Analysis-Directed Chemotherapy Assignment based on gene expression.
Age, Categorical <=18 years	0 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	37 Participants n=93 Participants
Age, Categorical >=65 years	16 Participants n=93 Participants
Age, Customized	63 years n=93 Participants
Sex: Female, Male Female	22 Participants n=93 Participants
Sex: Female, Male Male	31 Participants n=93 Participants
Region of Enrollment United States	53 participants n=93 Participants

PRIMARY outcome

Timeframe: 24 Months

Population: All participants were analyzed according to Response Evaluation Criteria in Solid Tumors (RECIST).

Outcome measures

Outcome measures
Measure	Double Agent Chemotherapy n=53 Participants Molecular Analysis-Directed Chemotherapy Assignment based on gene expression. Complete Response (CR): disappearance of all target lesions. Partial Response (PR): at least a 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference the baseline sum LD. Progressive Disease (PD): at least a 20% increase in the sum of LD of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable Disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum LD since the treatment started.
Best Disease Response After a Maximum of Six Cycles. Complete Response (CR)	0 Participants
Best Disease Response After a Maximum of Six Cycles. Partial Response (PR)	23 Participants
Best Disease Response After a Maximum of Six Cycles. Stable Disease (SD)	23 Participants
Best Disease Response After a Maximum of Six Cycles. Progressive Disease (PD)	6 Participants
Best Disease Response After a Maximum of Six Cycles. Not Assessible	1 Participants

SECONDARY outcome

Timeframe: 24 Months

Population: Review of all participants per protocol for Number at risk, Number of events, Number censored.

Median Overall Survival of Participants. OS and Progression Free Survival (PFS) probabilities were estimated using the Kaplan-Meier method. For statistical purposes, it is important to note that this trial was not designed to compare outcomes among patients assigned to the different chemotherapies, but rather that molecular analysis directed individualized chemotherapy assignment is feasible and yields promising results in outcomes.

Outcome measures

Outcome measures
Measure	Double Agent Chemotherapy n=53 Participants Molecular Analysis-Directed Chemotherapy Assignment based on gene expression. Complete Response (CR): disappearance of all target lesions. Partial Response (PR): at least a 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference the baseline sum LD. Progressive Disease (PD): at least a 20% increase in the sum of LD of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable Disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum LD since the treatment started.
Overall Survival (OS)	13.3 Months Interval 6.0 to 24.0

SECONDARY outcome

Timeframe: 24 Months

Population: Review of all participants for Number at risk, Number of events, Number censored.

PFS was recorded as the time elapsed from the date of first treatment to the date of first evidence for disease progression or death. OS and PFS probabilities were estimated using the Kaplan-Meier method. For statistical purposes, it is important to note that this trial was not designed to compare outcomes among patients assigned to the different chemotherapies, but rather that molecular analysis directed individualized chemotherapy assignment is feasible and yields promising results in outcomes.

Outcome measures

Outcome measures
Measure	Double Agent Chemotherapy n=53 Participants Molecular Analysis-Directed Chemotherapy Assignment based on gene expression. Complete Response (CR): disappearance of all target lesions. Partial Response (PR): at least a 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference the baseline sum LD. Progressive Disease (PD): at least a 20% increase in the sum of LD of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable Disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum LD since the treatment started.
Progression Free Survival (PFS)	6.6 Months Interval 6.0 to 24.0

Adverse Events

Double Agent Chemotherapy

Serious events: 29 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Double Agent Chemotherapy n=53 participants at risk Molecular Analysis-Directed Chemotherapy Assignment based on gene expression.
General disorders Dehydration - Grade 5	1.9% 1/53 • Number of events 1 • 24 Months Toxicity was recorded according to the Common Terminology Criteria for Adverse Events version 3 (http://ctep.cancer.gov).
Respiratory, thoracic and mediastinal disorders Dyspnea - Grade 3	3.8% 2/53 • Number of events 2 • 24 Months Toxicity was recorded according to the Common Terminology Criteria for Adverse Events version 3 (http://ctep.cancer.gov).
General disorders FN-ANC <1.0/Fever >=38.5C - Grade 3	3.8% 2/53 • Number of events 2 • 24 Months Toxicity was recorded according to the Common Terminology Criteria for Adverse Events version 3 (http://ctep.cancer.gov).
General disorders Fatigue - Grade 3	7.5% 4/53 • Number of events 5 • 24 Months Toxicity was recorded according to the Common Terminology Criteria for Adverse Events version 3 (http://ctep.cancer.gov).
General disorders Hand/Foot Syndrome - Grade 3	3.8% 2/53 • Number of events 2 • 24 Months Toxicity was recorded according to the Common Terminology Criteria for Adverse Events version 3 (http://ctep.cancer.gov).
Blood and lymphatic system disorders Hemoglobin - Grade 3	3.8% 2/53 • Number of events 2 • 24 Months Toxicity was recorded according to the Common Terminology Criteria for Adverse Events version 3 (http://ctep.cancer.gov).
Blood and lymphatic system disorders Hyperglycemia - Grade 3	3.8% 2/53 • Number of events 2 • 24 Months Toxicity was recorded according to the Common Terminology Criteria for Adverse Events version 3 (http://ctep.cancer.gov).
Blood and lymphatic system disorders Hypokalemia - Grade 3	3.8% 2/53 • Number of events 2 • 24 Months Toxicity was recorded according to the Common Terminology Criteria for Adverse Events version 3 (http://ctep.cancer.gov).
General disorders Hyponatremia - Grade 3	5.7% 3/53 • Number of events 4 • 24 Months Toxicity was recorded according to the Common Terminology Criteria for Adverse Events version 3 (http://ctep.cancer.gov).
General disorders Hypoxia - Grade 3	1.9% 1/53 • Number of events 1 • 24 Months Toxicity was recorded according to the Common Terminology Criteria for Adverse Events version 3 (http://ctep.cancer.gov).
General disorders International Normalization Ratio (INR) - Grade 3	1.9% 1/53 • Number of events 1 • 24 Months Toxicity was recorded according to the Common Terminology Criteria for Adverse Events version 3 (http://ctep.cancer.gov).
Vascular disorders Intracranial Hemorrhage - Grade 5	1.9% 1/53 • Number of events 1 • 24 Months Toxicity was recorded according to the Common Terminology Criteria for Adverse Events version 3 (http://ctep.cancer.gov).
General disorders Lacrimation - Grade 3	1.9% 1/53 • Number of events 1 • 24 Months Toxicity was recorded according to the Common Terminology Criteria for Adverse Events version 3 (http://ctep.cancer.gov).
Blood and lymphatic system disorders Leukocytes - Grade 3	13.2% 7/53 • Number of events 9 • 24 Months Toxicity was recorded according to the Common Terminology Criteria for Adverse Events version 3 (http://ctep.cancer.gov).
Blood and lymphatic system disorders Lymphocytes - Grade 3	20.8% 11/53 • Number of events 11 • 24 Months Toxicity was recorded according to the Common Terminology Criteria for Adverse Events version 3 (http://ctep.cancer.gov).
General disorders Nail Changes - Grade 3	1.9% 1/53 • Number of events 1 • 24 Months Toxicity was recorded according to the Common Terminology Criteria for Adverse Events version 3 (http://ctep.cancer.gov).
General disorders Neuropathy-Motor - Grade 3	1.9% 1/53 • Number of events 1 • 24 Months Toxicity was recorded according to the Common Terminology Criteria for Adverse Events version 3 (http://ctep.cancer.gov).
General disorders Neuropathy-Sensory - Grade 3	1.9% 1/53 • Number of events 1 • 24 Months Toxicity was recorded according to the Common Terminology Criteria for Adverse Events version 3 (http://ctep.cancer.gov).
General disorders Neutropenia - Grade 3	3.8% 2/53 • Number of events 3 • 24 Months Toxicity was recorded according to the Common Terminology Criteria for Adverse Events version 3 (http://ctep.cancer.gov).
General disorders Neutropenia - Grade 4	1.9% 1/53 • Number of events 1 • 24 Months Toxicity was recorded according to the Common Terminology Criteria for Adverse Events version 3 (http://ctep.cancer.gov).
General disorders Neutrophils - Grade 3	9.4% 5/53 • Number of events 5 • 24 Months Toxicity was recorded according to the Common Terminology Criteria for Adverse Events version 3 (http://ctep.cancer.gov).
General disorders Pain/Nausea/Vomiting - Grade 3	1.9% 1/53 • Number of events 1 • 24 Months Toxicity was recorded according to the Common Terminology Criteria for Adverse Events version 3 (http://ctep.cancer.gov).
General disorders Pedal Edema - Grade 3	1.9% 1/53 • Number of events 1 • 24 Months Toxicity was recorded according to the Common Terminology Criteria for Adverse Events version 3 (http://ctep.cancer.gov).
Blood and lymphatic system disorders Platelet Count - Grade 3	1.9% 1/53 • Number of events 1 • 24 Months Toxicity was recorded according to the Common Terminology Criteria for Adverse Events version 3 (http://ctep.cancer.gov).
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism - Grade 4	1.9% 1/53 • Number of events 1 • 24 Months Toxicity was recorded according to the Common Terminology Criteria for Adverse Events version 3 (http://ctep.cancer.gov).
Respiratory, thoracic and mediastinal disorders RLL DVT - Grade 3	1.9% 1/53 • Number of events 1 • 24 Months Toxicity was recorded according to the Common Terminology Criteria for Adverse Events version 3 (http://ctep.cancer.gov).
Vascular disorders Syncope - Grade 3	1.9% 1/53 • Number of events 1 • 24 Months Toxicity was recorded according to the Common Terminology Criteria for Adverse Events version 3 (http://ctep.cancer.gov).
Blood and lymphatic system disorders Thrombocytopenia - Grade 3	1.9% 1/53 • Number of events 1 • 24 Months Toxicity was recorded according to the Common Terminology Criteria for Adverse Events version 3 (http://ctep.cancer.gov).
General disorders Allergic Reaction - Grade 3	1.9% 1/53 • Number of events 1 • 24 Months Toxicity was recorded according to the Common Terminology Criteria for Adverse Events version 3 (http://ctep.cancer.gov).
Blood and lymphatic system disorders Anemia - Grade 3	1.9% 1/53 • Number of events 1 • 24 Months Toxicity was recorded according to the Common Terminology Criteria for Adverse Events version 3 (http://ctep.cancer.gov).
Respiratory, thoracic and mediastinal disorders Cough - Grade 3	1.9% 1/53 • Number of events 1 • 24 Months Toxicity was recorded according to the Common Terminology Criteria for Adverse Events version 3 (http://ctep.cancer.gov).
Respiratory, thoracic and mediastinal disorders Death not associated with CTCAE term - Grade 5	1.9% 1/53 • Number of events 1 • 24 Months Toxicity was recorded according to the Common Terminology Criteria for Adverse Events version 3 (http://ctep.cancer.gov).

Other adverse events

Other adverse events
Measure	Double Agent Chemotherapy n=53 participants at risk Molecular Analysis-Directed Chemotherapy Assignment based on gene expression.
Blood and lymphatic system disorders Hemoglobin - Grade 1	1.9% 1/53 • Number of events 1 • 24 Months Toxicity was recorded according to the Common Terminology Criteria for Adverse Events version 3 (http://ctep.cancer.gov).
Blood and lymphatic system disorders Hypokalemia - Grade 1	1.9% 1/53 • Number of events 1 • 24 Months Toxicity was recorded according to the Common Terminology Criteria for Adverse Events version 3 (http://ctep.cancer.gov).
Blood and lymphatic system disorders Leukocytes - Grade 1	1.9% 1/53 • Number of events 2 • 24 Months Toxicity was recorded according to the Common Terminology Criteria for Adverse Events version 3 (http://ctep.cancer.gov).
Blood and lymphatic system disorders Lymphocytes - Grade 1	1.9% 1/53 • Number of events 1 • 24 Months Toxicity was recorded according to the Common Terminology Criteria for Adverse Events version 3 (http://ctep.cancer.gov).
Blood and lymphatic system disorders Platelet Count - Grade 1	1.9% 1/53 • Number of events 1 • 24 Months Toxicity was recorded according to the Common Terminology Criteria for Adverse Events version 3 (http://ctep.cancer.gov).

Additional Information

Gerald Bepler, M.D., via Moffitt Cancer Center

Karmanos Cancer Institute (formerly at Moffitt Cancer Center)

Phone: 813-745-4398

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place