Erlotinib vs. Standard Chemotherapy in Patients With Advanced Non-small Cell Lung Cancer (NSCLC) and Eastern Cooperative Oncology Group (ECOG)Performance Status (PS) 2
Sponsor
OSI Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT00085839
Collaborator
(none)
103
19
2
36.9
5.4
0.1
Study Details
Study Description
Brief Summary
The purpose of this noncomparative study is to obtain preliminary estimates of the efficacy of erlotinib and standard chemotherapy in patients with advanced, previously untreated nonsmall cell lung cancer (NSCLC) and an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2. The study will also evaluate the safety of single-agent erlotinib in this patient population.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
103 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized Phase II Study of Single Agent Erlotinib [Tarceva (TM), OSI-774] Versus Standard Chemotherapy in Patients With Previously Untreated Advanced NSCLC and a Poor Performance Status
Study Start Date
:
Feb 1, 2004
Actual Primary Completion Date
:
Mar 1, 2007
Actual Study Completion Date
:
Mar 1, 2007
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Erlotinib Erlotinib tablets administered orally, 150 mg/day (starting dose) or 100 mg/day (reduced dose), continuous therapy |
Drug: Tarceva (Trademark) (erlotinib HCl, OSI-774)
Erlotinib tablets administered orally, 150 mg/day (starting dose) or 100 mg/day (reduced dose), continuous therapy
|
| Active Comparator: Standard Chemotherapy Paclitaxel 200 mg/m^2 IV infusion over 3 hours and carboplatin AUC 6 mg/mL x min IV over 15 - 30 minutes, both given on Day 1 every 21 days for 4 cycles |
Drug: Combination carboplatin and paclitaxel
Paclitaxel 200 mg/m^2 IV infusion over 3 hours and carboplatin AUC 6 mg/mL x min IV over 15 - 30 minutes, both given on Day 1 every 21 days for 4 cycles
|
Outcome Measures
Primary Outcome Measures
- Progression-free Survival [Until time of disease progression (maximum 5 months)]
Median time until disease progression. Disease progression defined as radiological and/or symptomatic disease progression or death in absence of progression.
Secondary Outcome Measures
- Overall Survival [From first study treatment until time of death (maximum 26.8 months)]
Median number of months from first study treatment until time of death
- Best Tumor Response [While receiving study treatment (maximum 60 weeks)]
Change in size of tumor: Complete Response (CR) = no measurable tumor; Partial Response (PR) = 30% decrease in size of measurable tumor; Stable Disease (SD) = measurable tumor size has not changed; Progressive Disease (PD) = measurable tumor 20% larger than at baseline.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Stage IIIB or IV Nonsmall cell lung cancer (NSCLC)
-
No prior chemotherapy
-
Eastern Cooperative Oncology Group (ECOG) Performance Status 2
-
Clinically or radiologically measurable disease per RECIST criteria
Exclusion Criteria:
-
Gastro-intestinal abnormalities
-
Any concurrent anticancer therapy
-
Prior treatment with epidermal growth factor receptor (EGFR) inhibitors of any kind
-
Other active malignancies
-
Uncontrolled brain metastases
-
Severe abnormalities of the cornea
-
Significant cardiac disease
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | California Cancer Care, Inc. | Greenbrae | California | United States | 94904 |
| 2 | Sharp Clinical Oncology Research | San Diego | California | United States | 92123 |
| 3 | Holy Cross Hospital | Fort Lauderdale | Florida | United States | 33308 |
| 4 | Mount Sinai Cancer Center | Miami Beach | Florida | United States | 33140 |
| 5 | University of Miami | Miami | Florida | United States | 33136 |
| 6 | Evanston Northwestern Healthcare | Evanston | Illinois | United States | 60201 |
| 7 | Oncology/Hematology Associates of Central Illinois | Peoria | Illinois | United States | 61615 |
| 8 | Norton Healthcare, Inc. | Louisville | Kentucky | United States | 40202 |
| 9 | Maryland Hematology/Oncology Associates | Baltimore | Maryland | United States | 21237 |
| 10 | VA Sierra Nevada Health Care System | Reno | Nevada | United States | 89502 |
| 11 | Weill Medical College of Cornell University | New York | New York | United States | 10021 |
| 12 | FEK Addo, PC | Bismarck | North Dakota | United States | 58503 |
| 13 | Gabrail Cancer Center | Canton | Ohio | United States | 44718 |
| 14 | University Hospitals of Cleveland | Cleveland | Ohio | United States | 44106 |
| 15 | Ohio State University | Columbus | Ohio | United States | 43210-1240 |
| 16 | Thomas Jefferson University Hospital | Philadelphia | Pennsylvania | United States | 19107 |
| 17 | Charleston Hematology Oncology | Charleston | South Carolina | United States | 29403 |
| 18 | East Tennessee Oncology/Hematology, PC | Knoxville | Tennessee | United States | 37920 |
| 19 | Sarah Cannon Cancer Center | Nashville | Tennessee | United States | 37203 |
Sponsors and Collaborators
- OSI Pharmaceuticals
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
OSI Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00085839
Other Study ID Numbers:
- OSI-774-201
First Posted:
Jun 17, 2004
Last Update Posted:
Aug 9, 2012
Last Verified:
Aug 1, 2012
Keywords provided by OSI Pharmaceuticals
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | The first patient was treated 17 March 2004 and the last patient completed 19 March 2007. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Erlotinib | Standard Chemotherapy |
|---|---|---|
| Arm/Group Description | Erlotinib 150 mg/day continuous therapy | Paclitaxel 200 mg/m^2 IV infusion over 3 hours and carboplatin AUC 6 mg/mL x min IV over 15 - 30 minutes, both given on Day 1 every 21 days for 4 cycles |
| Period Title: Overall Study | ||
| STARTED | 52 | 51 |
| COMPLETED | 52 | 51 |
| NOT COMPLETED | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Erlotinib | Standard Chemotherapy | Total |
|---|---|---|---|
| Arm/Group Description | Erlotinib 150 mg/day continuous therapy | Paclitaxel 200 mg/m^2 IV infusion over 3 hours and carboplatin AUC 6 mg/mL x min IV over 15 - 30 minutes, both given on Day 1 every 21 days for 4 cycles | Total of all reporting groups |
| Overall Participants | 52 | 51 | 103 |
| Age (years) [Median (Full Range) ] | |||
| Median (Full Range) [years] |
69
|
67
|
68
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
29
55.8%
|
23
45.1%
|
52
50.5%
|
| Male |
23
44.2%
|
28
54.9%
|
51
49.5%
|
| Race/Ethnicity, Customized (participants) [Number] | |||
| White |
35
67.3%
|
33
64.7%
|
68
66%
|
| Black |
12
23.1%
|
10
19.6%
|
22
21.4%
|
| Hispanic |
4
7.7%
|
7
13.7%
|
11
10.7%
|
| Asian |
1
1.9%
|
1
2%
|
2
1.9%
|
Outcome Measures
| Title | Progression-free Survival |
|---|---|
| Description | Median time until disease progression. Disease progression defined as radiological and/or symptomatic disease progression or death in absence of progression. |
| Time Frame | Until time of disease progression (maximum 5 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who received at least 1 dose of study drug and who had both a baseline and at least one on-treatment tumor assessment. |
| Arm/Group Title | Erlotinib | Standard Chemotherapy |
|---|---|---|
| Arm/Group Description | Erlotinib 150 mg/day continuous therapy | Paclitaxel 200 mg/m^2 IV infusion over 3 hours and carboplatin AUC 6 mg/mL x min IV over 15 - 30 minutes, both given on Day 1 every 21 days for 4 cycles |
| Measure Participants | 52 | 51 |
| Median (95% Confidence Interval) [months] |
1.91
|
3.52
|
| Title | Overall Survival |
|---|---|
| Description | Median number of months from first study treatment until time of death |
| Time Frame | From first study treatment until time of death (maximum 26.8 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who received at least 1 dose of study drug and who had both a baseline and at least one on-treatment tumor assessment. |
| Arm/Group Title | Erlotinib | Standard Chemotherapy |
|---|---|---|
| Arm/Group Description | Erlotinib 150 mg/day continuous therapy | Paclitaxel 200 mg/m^2 IV infusion over 3 hours and carboplatin AUC 6 mg/mL x min IV over 15 - 30 minutes, both given on Day 1 every 21 days for 4 cycles |
| Measure Participants | 52 | 51 |
| Median (95% Confidence Interval) [months] |
6.57
|
9.53
|
| Title | Best Tumor Response |
|---|---|
| Description | Change in size of tumor: Complete Response (CR) = no measurable tumor; Partial Response (PR) = 30% decrease in size of measurable tumor; Stable Disease (SD) = measurable tumor size has not changed; Progressive Disease (PD) = measurable tumor 20% larger than at baseline. |
| Time Frame | While receiving study treatment (maximum 60 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who received at least 1 dose of study drug and who had both a baseline and at least one on-treatment tumor assessment. |
| Arm/Group Title | Erlotinib | Standard Chemotherapy |
|---|---|---|
| Arm/Group Description | Erlotinib 150 mg/day continuous therapy | Paclitaxel 200 mg/m^2 IV infusion over 3 hours and carboplatin AUC 6 mg/mL x min IV over 15 - 30 minutes, both given on Day 1 every 21 days for 4 cycles |
| Measure Participants | 52 | 51 |
| Complete Response (CR) |
0
0%
|
0
0%
|
| Partial Response (PR) |
2
3.8%
|
6
11.8%
|
| Stable Disease (SD) |
19
36.5%
|
23
45.1%
|
| Progressive Disease (PD) |
23
44.2%
|
10
19.6%
|
| Unable to Determine/Not Evaluable |
8
15.4%
|
12
23.5%
|
Adverse Events
| Time Frame | While on study drug and 30 days after last dose | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Adverse events are provided regardless of causality; safety population includes patients who received at least one dose of study drug. | |||
| Arm/Group Title | Erlotinib | Standard Chemotherapy | ||
| Arm/Group Description | Erlotinib 150 mg/day continuous therapy | Paclitaxel 200 mg/m^2 IV infusion over 3 hours and carboplatin AUC 6 mg/mL x min IV over 15 - 30 minutes, both given on Day 1 every 21 days for 4 cycles | ||
All Cause Mortality |
||||
| Erlotinib | Standard Chemotherapy | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Erlotinib | Standard Chemotherapy | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 24/52 (46.2%) | 13/51 (25.5%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 0/52 (0%) | 2/51 (3.9%) | ||
| Febrile neutropenia | 0/52 (0%) | 2/51 (3.9%) | ||
| Neutropenia | 0/52 (0%) | 1/51 (2%) | ||
| Cardiac disorders | ||||
| Atrial fibrillation | 2/52 (3.8%) | 1/51 (2%) | ||
| Cardiac failure congestive | 1/52 (1.9%) | 0/51 (0%) | ||
| Cardiac fibrillation | 1/52 (1.9%) | 0/51 (0%) | ||
| Cardiac tamponade | 1/52 (1.9%) | 0/51 (0%) | ||
| Ventricular fibrillation | 1/52 (1.9%) | 0/51 (0%) | ||
| Acute myocardial infarction | 0/52 (0%) | 1/51 (2%) | ||
| Myocardial infarction | 0/52 (0%) | 1/51 (2%) | ||
| Pericardial effusion | 0/52 (0%) | 1/51 (2%) | ||
| Eye disorders | ||||
| Optic neuritis | 1/52 (1.9%) | 0/51 (0%) | ||
| Gastrointestinal disorders | ||||
| Vomiting | 2/52 (3.8%) | 1/51 (2%) | ||
| Dysphagia | 1/52 (1.9%) | 0/51 (0%) | ||
| Gastrointestinal haemorrhage | 1/52 (1.9%) | 0/51 (0%) | ||
| Impaired gastric emptying | 1/52 (1.9%) | 0/51 (0%) | ||
| Abdominal pain | 0/52 (0%) | 1/51 (2%) | ||
| Constipation | 0/52 (0%) | 1/51 (2%) | ||
| Gastric ulcer perforation | 0/52 (0%) | 1/51 (2%) | ||
| General disorders | ||||
| Death | 1/52 (1.9%) | 0/51 (0%) | ||
| Chest discomfort | 0/52 (0%) | 1/51 (2%) | ||
| Infections and infestations | ||||
| Pneumonia | 2/52 (3.8%) | 0/51 (0%) | ||
| Endocarditis | 1/52 (1.9%) | 0/51 (0%) | ||
| Gastroenteritis viral | 1/52 (1.9%) | 0/51 (0%) | ||
| Pneumonia haemophilus | 1/52 (1.9%) | 0/51 (0%) | ||
| Sepsis | 1/52 (1.9%) | 0/51 (0%) | ||
| Staphylococcal bacteraemia | 1/52 (1.9%) | 0/51 (0%) | ||
| Urinary tract infection | 1/52 (1.9%) | 0/51 (0%) | ||
| Viral diarrhoea | 1/52 (1.9%) | 0/51 (0%) | ||
| Streptococcal infection | 0/52 (0%) | 1/51 (2%) | ||
| Investigations | ||||
| International normalised ratio increased | 0/52 (0%) | 1/51 (2%) | ||
| Metabolism and nutrition disorders | ||||
| Dehydration | 1/52 (1.9%) | 1/51 (2%) | ||
| Hypercalcaemia | 0/52 (0%) | 1/51 (2%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Muscular weakness | 1/52 (1.9%) | 0/51 (0%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Malignant pleural effusion | 1/52 (1.9%) | 0/51 (0%) | ||
| Metastatic pain | 1/52 (1.9%) | 0/51 (0%) | ||
| Pericardial effusion malignant | 1/52 (1.9%) | 0/51 (0%) | ||
| Nervous system disorders | ||||
| Brain oedema | 0/52 (0%) | 1/51 (2%) | ||
| Cerebral haemorrhage | 0/52 (0%) | 2/51 (3.9%) | ||
| Convulsion | 0/52 (0%) | 1/51 (2%) | ||
| Psychiatric disorders | ||||
| Mental status changes | 1/52 (1.9%) | 0/51 (0%) | ||
| Renal and urinary disorders | ||||
| Renal failure acute | 1/52 (1.9%) | 0/51 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Dyspnoea | 4/52 (7.7%) | 1/51 (2%) | ||
| Hypoxia | 2/52 (3.8%) | 0/51 (0%) | ||
| Pulmonary embolism | 2/52 (3.8%) | 0/51 (0%) | ||
| Haemoptysis | 1/52 (1.9%) | 0/51 (0%) | ||
| Lung infiltration | 1/52 (1.9%) | 0/51 (0%) | ||
| Pneumonitis | 1/52 (1.9%) | 0/51 (0%) | ||
| Pulmonary fibrosis | 1/52 (1.9%) | 0/51 (0%) | ||
| Pneumonia aspiration | 0/52 (0%) | 1/51 (2%) | ||
| Vascular disorders | ||||
| Deep vein thrombosis | 1/52 (1.9%) | 3/51 (5.9%) | ||
| Ischaemic limb pain | 1/52 (1.9%) | 0/51 (0%) | ||
| Vena cava thrombosis | 1/52 (1.9%) | 0/51 (0%) | ||
| Hypotention | 0/52 (0%) | 1/51 (2%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Erlotinib | Standard Chemotherapy | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 51/52 (98.1%) | 50/51 (98%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 5/52 (9.6%) | 10/51 (19.6%) | ||
| Neutropenia | 0/52 (0%) | 4/51 (7.8%) | ||
| Cardiac disorders | ||||
| Tachycardia | 1/52 (1.9%) | 3/51 (5.9%) | ||
| Eye disorders | ||||
| Vision blurred | 2/52 (3.8%) | 3/51 (5.9%) | ||
| Keratoconjunctivitis sicca | 2/52 (3.8%) | 2/51 (3.9%) | ||
| Lacrimation increased | 3/52 (5.8%) | 1/51 (2%) | ||
| Gastrointestinal disorders | ||||
| Nausea | 18/52 (34.6%) | 27/51 (52.9%) | ||
| Diarrhoea | 24/52 (46.2%) | 15/51 (29.4%) | ||
| Vomiting | 12/52 (23.1%) | 15/51 (29.4%) | ||
| Constipation | 11/52 (21.2%) | 14/51 (27.5%) | ||
| Dyspepsia | 6/52 (11.5%) | 3/51 (5.9%) | ||
| Stomatitis | 6/52 (11.5%) | 3/51 (5.9%) | ||
| Abdominal pain | 2/52 (3.8%) | 5/51 (9.8%) | ||
| Dysphagia | 3/52 (5.8%) | 2/51 (3.9%) | ||
| Abdominal pain upper | 1/52 (1.9%) | 3/51 (5.9%) | ||
| Dysgeusia | 4/52 (7.7%) | 0/51 (0%) | ||
| General disorders | ||||
| Fatigue | 19/52 (36.5%) | 23/51 (45.1%) | ||
| Oedema peripheral | 4/52 (7.7%) | 8/51 (15.7%) | ||
| Asthenia | 2/52 (3.8%) | 4/51 (7.8%) | ||
| Injury, poisoning and procedural complications | ||||
| Contusion | 4/52 (7.7%) | 1/51 (2%) | ||
| Investigations | ||||
| Weight decreased | 12/52 (23.1%) | 6/51 (11.8%) | ||
| Metabolism and nutrition disorders | ||||
| Anorexia | 18/52 (34.6%) | 16/51 (31.4%) | ||
| Dehydration | 4/52 (7.7%) | 4/51 (7.8%) | ||
| Decreased appetite | 4/52 (7.7%) | 2/51 (3.9%) | ||
| Hypokalaemia | 2/52 (3.8%) | 4/51 (7.8%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 4/52 (7.7%) | 13/51 (25.5%) | ||
| Myalgia | 2/52 (3.8%) | 10/51 (19.6%) | ||
| Back pain | 3/52 (5.8%) | 4/51 (7.8%) | ||
| Pain in extremity | 2/52 (3.8%) | 5/51 (9.8%) | ||
| Bone pain | 3/52 (5.8%) | 2/51 (3.9%) | ||
| Chest wall pain | 3/52 (5.8%) | 2/51 (3.9%) | ||
| Nervous system disorders | ||||
| Dizziness | 9/52 (17.3%) | 2/51 (3.9%) | ||
| Headache | 5/52 (9.6%) | 5/51 (9.8%) | ||
| Paraesthesia | 2/52 (3.8%) | 6/51 (11.8%) | ||
| Peripheral sensory neuropathy | 0/52 (0%) | 8/51 (15.7%) | ||
| Neuropathy peripheral | 0/52 (0%) | 7/51 (13.7%) | ||
| Hypoaesthesia | 1/52 (1.9%) | 3/51 (5.9%) | ||
| Tremor | 3/52 (5.8%) | 1/51 (2%) | ||
| Psychiatric disorders | ||||
| Insomnia | 1/52 (1.9%) | 7/51 (13.7%) | ||
| Anxiety | 2/52 (3.8%) | 4/51 (7.8%) | ||
| Confusional state | 2/52 (3.8%) | 2/51 (3.9%) | ||
| Depression | 3/52 (5.8%) | 1/51 (2%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Dyspnoea | 10/52 (19.2%) | 12/51 (23.5%) | ||
| Cough | 6/52 (11.5%) | 3/51 (5.9%) | ||
| Epistaxis | 7/52 (13.5%) | 1/51 (2%) | ||
| Dyspnoea exertional | 3/52 (5.8%) | 2/51 (3.9%) | ||
| Productive cough | 1/52 (1.9%) | 3/51 (5.9%) | ||
| Wheezing | 3/52 (5.8%) | 1/51 (2%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Alopecia | 6/52 (11.5%) | 26/51 (51%) | ||
| Dermatitis acneiform | 13/52 (25%) | 1/51 (2%) | ||
| Rash | 12/52 (23.1%) | 2/51 (3.9%) | ||
| Pruritus | 9/52 (17.3%) | 4/51 (7.8%) | ||
| Dermatitis exfoliative | 8/52 (15.4%) | 0/51 (0%) | ||
| Dry skin | 5/52 (9.6%) | 1/51 (2%) | ||
| Rash maculo-papular | 4/52 (7.7%) | 0/51 (0%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Medical Monitor |
|---|---|
| Organization | Astellas Pharma Global Development |
| Phone | |
| clinicaltrials@us.astellas.com |
Responsible Party:
OSI Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00085839
Other Study ID Numbers:
- OSI-774-201
First Posted:
Jun 17, 2004
Last Update Posted:
Aug 9, 2012
Last Verified:
Aug 1, 2012