Trial Outcomes & Findings for Preoperative Pemetrexed and Carboplatin for Select Stage IB, II, and III Non-Squamous Non-Small-Cell Lung Cancer (NCT NCT00906282)
NCT ID: NCT00906282
Last Updated: 2017-02-24
Results Overview
The percentage of patients who were alive at 3 years from time of first study treatment until date of death from any cause. Overall survival is shown for the Intent-to-Treat population.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
46 participants
Primary outcome timeframe
36 months
Results posted on
2017-02-24
Participant Flow
Between Aug 2009 and Jul 2013, 46 patients with potentially resectable non-squamous NSCLC were enrolled from 10 participating sites in the U.S.
Patients (pts) received up to 4 cycles (12 weeks) of preoperative chemotherapy and were restaged after 6 and 12 weeks. Pts with progressive disease or intolerable toxicity came off study; pts who remained surgical candidates had resection at weeks 15-18. Following resection pts received no further planned protocol treatment.
Participant milestones
| Measure |
Pemetrexed/Carboplatin/Surgery
Up to 12 weeks of preoperative chemotherapy:
* Pemetrexed: 500 mg/m2 intravenously (IV) for 10 minutes on Day 1 each cycle;
* Carboplatin: AUC 6.0 by IV over 30-60 minutes on Day 1 each cycle
Weeks 15-18: Patients deemed surgical candidates will have resection.
|
|---|---|
|
Preoperative Chemotherapy
STARTED
|
46
|
|
Preoperative Chemotherapy
COMPLETED
|
27
|
|
Preoperative Chemotherapy
NOT COMPLETED
|
19
|
|
Surgical Resection
STARTED
|
27
|
|
Surgical Resection
COMPLETED
|
27
|
|
Surgical Resection
NOT COMPLETED
|
0
|
Reasons for withdrawal
| Measure |
Pemetrexed/Carboplatin/Surgery
Up to 12 weeks of preoperative chemotherapy:
* Pemetrexed: 500 mg/m2 intravenously (IV) for 10 minutes on Day 1 each cycle;
* Carboplatin: AUC 6.0 by IV over 30-60 minutes on Day 1 each cycle
Weeks 15-18: Patients deemed surgical candidates will have resection.
|
|---|---|
|
Preoperative Chemotherapy
Withdrawal by Subject
|
2
|
|
Preoperative Chemotherapy
Not surgical candidates, off study
|
10
|
|
Preoperative Chemotherapy
Progressive disease
|
6
|
|
Preoperative Chemotherapy
Toxicity
|
1
|
Baseline Characteristics
Preoperative Pemetrexed and Carboplatin for Select Stage IB, II, and III Non-Squamous Non-Small-Cell Lung Cancer
Baseline characteristics by cohort
| Measure |
Pemetrexed/Carboplatin/Surgery
n=46 Participants
Up to 12 weeks (4 cycles) of preoperative treatment given on Day 1 of each 21-day cycle:
* Pemetrexed: 500 mg/m2 intravenously (IV) over 10 minutes
* Carboplatin: AUC 6.0, IV infused over 30-60 minutes
At weeks 15-18, surgical candidates will have resection.
|
|---|---|
|
Age, Continuous
|
65 years
n=5 Participants
|
|
Gender
Female
|
28 Participants
n=5 Participants
|
|
Gender
Male
|
18 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
42 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
African-American
|
4 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
46 participants
n=5 Participants
|
|
Clinical Stage of Cancer
Stage 1B
|
5 participants
n=5 Participants
|
|
Clinical Stage of Cancer
Stage IIA/II/B
|
17 participants
n=5 Participants
|
|
Clinical Stage of Cancer
Stage IIIA
|
23 participants
n=5 Participants
|
|
Clinical Stage of Cancer
Stage IIIB
|
1 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 36 monthsThe percentage of patients who were alive at 3 years from time of first study treatment until date of death from any cause. Overall survival is shown for the Intent-to-Treat population.
Outcome measures
| Measure |
Pemetrexed/Carboplatin/Surgery
n=46 Participants
Up to 12 weeks of preoperative chemotherapy:
* Pemetrexed: 500 mg/m2 intravenously (IV) for 10 minutes on Day 1 each cycle;
* Carboplatin: AUC 6.0 by IV over 30-60 minutes on Day 1 each cycle
Weeks 15-18: Patients deemed surgical candidates will have resection.
|
|---|---|
|
3-Year Overall Survival Rate
|
45 percentage of participants
Interval 30.0 to 60.0
|
SECONDARY outcome
Timeframe: At 6 and 12 weeksObjective Tumor Response defined as the percent of patients who completed up to 4 cycles of pre-operative chemotherapy and achieved a complete response (CR) or partial response (PR) assessed by Response Evaluation in Solid Tumors (RECIST) 1.0. Patients with stable disease (SD) or response to treatment were deemed surgical candidates. \[CR=disappearance of all target tumors; PR= ≥30% decrease in the sum of the longest diameters of target tumors. SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.\]
Outcome measures
| Measure |
Pemetrexed/Carboplatin/Surgery
n=46 Participants
Up to 12 weeks of preoperative chemotherapy:
* Pemetrexed: 500 mg/m2 intravenously (IV) for 10 minutes on Day 1 each cycle;
* Carboplatin: AUC 6.0 by IV over 30-60 minutes on Day 1 each cycle
Weeks 15-18: Patients deemed surgical candidates will have resection.
|
|---|---|
|
Objective Tumor Response
PR
|
41 percentage of participants
|
|
Objective Tumor Response
SD
|
48 percentage of participants
|
SECONDARY outcome
Timeframe: weeks 15 -18Percent of patients having a pathological complete or partial response (pCR or pPR) at surgery. pCR defined as complete removal of all tumor. pPR defined as residual viable tumor demonstrated in the resected specimen.
Outcome measures
| Measure |
Pemetrexed/Carboplatin/Surgery
n=27 Participants
Up to 12 weeks of preoperative chemotherapy:
* Pemetrexed: 500 mg/m2 intravenously (IV) for 10 minutes on Day 1 each cycle;
* Carboplatin: AUC 6.0 by IV over 30-60 minutes on Day 1 each cycle
Weeks 15-18: Patients deemed surgical candidates will have resection.
|
|---|---|
|
Pathologic Response Rate
pPR
|
100 percentage of participants
|
|
Pathologic Response Rate
pCR
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: At 15-18 weeksPopulation: The amount of residual tumor measured in centimeters (cm).
pPR was further assessed by the amount of residual tumor measured at surgery: microscopic residual disease = less than 1 centimeter (\<1 cm); macroscopic residual disease = 1 centimeter or greater (≥1 cm).
Outcome measures
| Measure |
Pemetrexed/Carboplatin/Surgery
n=27 Participants
Up to 12 weeks of preoperative chemotherapy:
* Pemetrexed: 500 mg/m2 intravenously (IV) for 10 minutes on Day 1 each cycle;
* Carboplatin: AUC 6.0 by IV over 30-60 minutes on Day 1 each cycle
Weeks 15-18: Patients deemed surgical candidates will have resection.
|
|---|---|
|
Rate of Residual Disease as an Assessment of Pathological Partial Response (pPR)
|
2.5 centimeters
Interval 0.5 to 9.5
|
SECONDARY outcome
Timeframe: At weeks 15-18The percent of patients who had surgical resection listed by procedure type: lobectomy or pneumonectomy, or resection of adjacent chest wall or mediastinal structures when appropriate. Surgery followed standard guidelines for resection of non-small-cell lung cancer (NSCLC).
Outcome measures
| Measure |
Pemetrexed/Carboplatin/Surgery
n=27 Participants
Up to 12 weeks of preoperative chemotherapy:
* Pemetrexed: 500 mg/m2 intravenously (IV) for 10 minutes on Day 1 each cycle;
* Carboplatin: AUC 6.0 by IV over 30-60 minutes on Day 1 each cycle
Weeks 15-18: Patients deemed surgical candidates will have resection.
|
|---|---|
|
Complete Resection Rate
Lobectomy
|
70 percentage of patients
|
|
Complete Resection Rate
Wedge Resection
|
15 percentage of patients
|
|
Complete Resection Rate
Pneumonectomy
|
11 percentage of patients
|
|
Complete Resection Rate
Bilobectomy
|
4 percentage of patients
|
Adverse Events
Pemetrexed/Carboplatin
Serious events: 18 serious events
Other events: 46 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Pemetrexed/Carboplatin
n=46 participants at risk
All patients who received at least 1 dose of study treatment were included in the safety analysis.
|
|---|---|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
4.3%
2/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Blood and lymphatic system disorders
Neutropenia
|
4.3%
2/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Blood and lymphatic system disorders
Anemia
|
4.3%
2/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Cardiac disorders
Atrial Fibrillation
|
2.2%
1/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Blood and lymphatic system disorders
Leukopenia
|
2.2%
1/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Infections and infestations
Anorectal cellulitis
|
2.2%
1/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Infections and infestations
Gastroenteritis
|
2.2%
1/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Infections and infestations
Pneumonia
|
2.2%
1/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Investigations
Neutrophil count decreased
|
2.2%
1/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Investigations
Platelet count
|
2.2%
1/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Investigations
Platelet count decreased
|
2.2%
1/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
2.2%
1/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Respiratory, thoracic and mediastinal disorders
Haemothorax
|
2.2%
1/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
2.2%
1/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
2.2%
1/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
Other adverse events
| Measure |
Pemetrexed/Carboplatin
n=46 participants at risk
All patients who received at least 1 dose of study treatment were included in the safety analysis.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
52.2%
24/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
47.8%
22/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Blood and lymphatic system disorders
Leukopenia
|
37.0%
17/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Blood and lymphatic system disorders
Neutropenia
|
39.1%
18/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Blood and lymphatic system disorders
Lymphopenia
|
8.7%
4/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
General disorders
Fatigue
|
78.3%
36/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
General disorders
Oedema Peripheral
|
10.9%
5/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
General disorders
Pyrexia
|
13.0%
6/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
General disorders
Mucosal Inflammation
|
10.9%
5/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
General disorders
Asthenia
|
6.5%
3/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
General disorders
Chest pain
|
6.5%
3/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
General disorders
Chills
|
6.5%
3/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Gastrointestinal disorders
Nausea
|
63.0%
29/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Gastrointestinal disorders
Constipation
|
54.3%
25/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Gastrointestinal disorders
Vomiting
|
32.6%
15/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Gastrointestinal disorders
Diarrhoea
|
21.7%
10/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Gastrointestinal disorders
Stomatitis
|
8.7%
4/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Gastrointestinal disorders
Dyspepsia
|
6.5%
3/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Investigations
Haemoglobin
|
19.6%
9/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Investigations
Platelet count decreased
|
8.7%
4/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Investigations
Platelet count
|
17.4%
8/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Investigations
Neutrophil count
|
17.4%
8/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Investigations
Neutrophil count decreased
|
10.9%
5/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Investigations
Weight decreased
|
13.0%
6/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Investigations
White blood cell count
|
10.9%
5/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Investigations
Haemoglobin decreased
|
8.7%
4/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Investigations
Blood creatinine decreased
|
6.5%
3/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Investigations
White blood cell count decreased
|
6.5%
3/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Investigations
Blood glucose increased
|
6.5%
3/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
30.4%
14/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
19.6%
9/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
10.9%
5/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea Exertional
|
6.5%
3/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
6.5%
3/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
17.4%
8/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Metabolism and nutrition disorders
Dehydration
|
19.6%
9/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Metabolism and nutrition disorders
Decreased appetite
|
17.4%
8/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Nervous system disorders
Dysgeusia
|
15.2%
7/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Nervous system disorders
Headache
|
10.9%
5/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Nervous system disorders
Dizziness
|
6.5%
3/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
8.7%
4/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
6.5%
3/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Psychiatric disorders
Insomnia
|
10.9%
5/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Skin and subcutaneous tissue disorders
Rash
|
10.9%
5/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
10.9%
5/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Skin and subcutaneous tissue disorders
Pruritis
|
8.7%
4/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Vascular disorders
Hypotension
|
10.9%
5/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Infections and infestations
Upper respiratory tract infection
|
6.5%
3/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
|
Infections and infestations
Urinary tract infection
|
6.5%
3/46 • Every 3 weeks up to 12 weeks during preoperative treatment, then every 3 months post surgery for years 1-2, and every 6 months thru years 3-5..
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The sponsor can review/embargo results communications prior to public release for a period that is \>60 days but ≤180 days from date submitted to sponsor, who may require changes to the communication in order to remove specifically identified confidential information (other than study data) and/or delay the proposed publication to enable the sponsor to seek patent protection for inventions. The PI may not publish its results until 18 mos. after the trial has been completed at all sites.
- Publication restrictions are in place
Restriction type: OTHER