A Study Of Cisplatin (Or Carboplatin) And Etoposide With Or Without Figitumumab (CP-751,871) In Patients With Extensive-Stage Small Cell Lung Cancer

• Sponsor: Pfizer (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00977561
• Collaborator: (none)
• Enrollment: 9
• Locations: 51
• Arms: 2
• Duration (Months): 18
• Patients Per Site: 0.2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This study will summarize the safety of patients receiving figitumumab combined with etoposide and cisplatin (or carboplatin) vs. patients receiving etoposide and cisplatin (or carboplatin) alone as first line treatment for extensive stage disease Small Cell Lung Cancer.

Condition or Disease	Intervention/Treatment	Phase
Small Cell Lung Carcinoma	Drug: figitumumab; Drug: Cisplatin (Or Carboplatin); Drug: Etoposide; Drug: Cisplatin (Or Carboplatin); Drug: Etoposide	Phase 2

Detailed Description

The study prematurely discontinued on January 26, 2011 due to slow enrollment. It should be noted that safety concerns have not been seen in this study and have not factored into this decision.

Study Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Randomized, Open Label Study Of Figitumumab (CP-751,871) Plus Cisplatin (Or Carboplatin) And Etoposide, Versus Cisplatin (Or Carboplatin) And Etoposide Alone, As First Line Treatment In Patients With Extensive Stage Disease Small Cell Lung Cancer
• Study Start Date: Apr 1, 2010
• Actual Primary Completion Date: Oct 1, 2011
• Actual Study Completion Date: Oct 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A Figitumumab (CP-751,871) Plus Chemotherapy [Cisplatin (Or Carboplatin) And Etoposide] All drugs to be administered on a 21 day cycle	Drug: figitumumab; Figitumumab (20 mg/kg); Drug: Cisplatin (Or Carboplatin); Cisplatin (75 mg/m2 IV on Day 1) or Carboplatin AUC 5; Drug: Etoposide; Etoposide (100 mg/m2 IV on Days 1, 2 and 3)
Active Comparator: Arm B Chemotherapy [Cisplatin (Or Carboplatin) And Etoposide] All drugs to be administered on a 21 day cycle	Drug: Cisplatin (Or Carboplatin); Cisplatin (75 mg/m2 IV on Day 1) or Carboplatin AUC 5; Drug: Etoposide; Etoposide (100 mg/m2 IV on Days 1, 2 and 3)

Outcome Measures

Primary Outcome Measures

1. Progression-Free Survival (PFS) [Baseline, every 2nd cycle (between Day 15-21, 1 cycle = 21 days) starting with Cycle 2 until disease progression, at the end of treatment visit (if more than 28 days have passed since last evaluation); and every 6 weeks until disease progression]

   Median time from the first dose of study treatment to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first. PFS time (days) = [event (progression or death) date or censor date - date of randomization + 1].

Secondary Outcome Measures

1. Number of Participants With Objective Response [Baseline, every 2nd cycle (between Day 15-21, 1 cycle = 21 days) starting with Cycle 2 until disease progression, at the end of treatment visit (if more than 28 days have passed since last evaluation); and every 6 weeks until disease progression]

   Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST.

2. Overall Survival (OS) [Every 3 months until death or 12 months from the date the last participant was randomized]

   Overall survival was the duration from enrollment to death due to any cause. For participants who are alive, overall survival was censored at the last contact. Survival time (days) = [death date (last known alive date) - date of randomization +1].

3. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Baseline up to follow-up (90 days post dose)]

   AEs are any untoward, undesired, or unplanned event in the form of signs, symptoms, disease, or laboratory or physiologic observations occurring in a person given study treatment. The event does not need to be causally related to the study treatment. SAEs include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly or birth defect in the offspring of a study subject.

4. Maximum Observed Plasma Concentration (Cmax) of Figitumumab [Cycle 1, Day 2; Day 1 of Cycles 2, 4, 5, 6, 10 and 15; Day 28 and Day 90 post last figitumumab dose]

5. Minimum Observed Plasma Trough Concentration (Cmin) of Figitumumab [Cycle 1, Day 2; Day 1 of Cycles 2, 4, 5, 6, 10 and 15; Day 28 and Day 90 post last figitumumab dose]

6. Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Etoposide [Cycles 1 and 2, Day 1 and Day 2 (within 3 hours prior to Day 1 etoposide infusion; 1, 1.5, 2, 3, 6, and 24 hours post Day 1 etoposide infusion); Cycles 4 and 5, Day 2: 24 hours post Day 1 etoposide infusion]

   Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)

7. Maximum Observed Plasma Concentration (Cmax) of Etoposide [Cycles 1 and 2, Day 1 and Day 2 (within 3 hours prior to Day 1 etoposide infusion; 1, 1.5, 2, 3, 6, and 24 hours post Day 1 etoposide infusion); Cycles 4 and 5, Day 2: 24 hours post Day 1 etoposide infusion]

8. Percentage of Participants Reporting Positive Anti-Drug Antibodies (ADA) Response for Figitumumab [Day 2 of Cycle 1 (or Day 1 of the initial cycle starting single agent figitumumab); Day 1 of Cycles 2 and 4; Day 28 and Day 90 post last figitumumab dose]

   Percentage of participants with positive total or neutralizing anti-drug antibody (ADA) for figitumumab

9. Cancer Dyspnea Scale (CDS) Score [Day 1 of every cycle (up to 17 cycles), at the end of treatment visit (28 days post last dose); then every 6 weeks until disease progression]

   The Cancer Dyspnea Scale consists of 12 questions that assess 3 domains of dyspnea (sense of effort, anxiety and discomfort) related to lung cancer. The questions are answered on 5-point Likert scale ranging from 1 to 5 (1 "Not at All" to 5 "Very Much").

10. Numeric Rating Scale (NRS) Score [Day 1 of every cycle (up to 17 cycles), at the end of treatment visit (28 days post last dose); then every 6 weeks until disease progression]

    The Numeric Rating Scale (NRS) is a 1-item self-reported questionnaire designed to assess "worst pain" severity. Overall scores range from 0 to 10, with low scores representing a lower level of pain.

11. Pre-treatment Levels of Tumor Biomarkers Involved in Insulin-Like Growth Factor 1 (IGF-I) Signaling Pathway [Baseline prior to dosing]

12. Levels of Serum Circulating Insulin-like Growth Factor (IGF) Pathway Related Markers [Baseline (Cycle 1, Day 1 prior to dosing), Cycle 4 (Day 1), at the end of treatment visit (28 days post last figitumumab dose)]

13. Number of Total Circulating Tumor-Related Cells (CTCs) and Insulin-Like Growth Factor 1 Receptor (IGF-IR)-Expressing CTCs [Baseline (Cycle 1, Day 1), Cycle 4 (Day 1) and at the end of treatment visit (28 days post last figitumumab dose)]

    Pre-treatment and post-treatment counts of total and IGF-IR-positive CTCs

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically confirmed diagnosis of extensive stage disease Small Cell Lung Cancer (SCLC), with tumor biopsy sample required.

• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. Total IGF-1 > or = 120 ng/ml

Exclusion Criteria:

• Any prior systemic therapy for Small Cell Lung Cancer (SCLC)

• HbA1c > or = 5.7%

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Washington	District of Columbia	United States	20007-2197
2	Pfizer Investigational Site	Washington	District of Columbia	United States	20007
3	Pfizer Investigational Site	Marrero	Louisiana	United States	70072
4	Pfizer Investigational Site	Metairie	Louisiana	United States	70006
5	Pfizer Investigational Site	Creve Coeur	Missouri	United States	63141
6	Pfizer Investigational Site	St. Louis	Missouri	United States	63110-1094
7	Pfizer Investigational Site	St. Louis	Missouri	United States	63110
8	Pfizer Investigational Site	St. Peters	Missouri	United States	63376
9	Pfizer Investigational Site	Morristown	New Jersey	United States	07962
10	Pfizer Investigational Site	Hickory	North Carolina	United States	28602
11	Pfizer Investigational Site	Kernersville	North Carolina	United States	27284
12	Pfizer Investigational Site	Lenoir	North Carolina	United States	28645
13	Pfizer Investigational Site	Lexington	North Carolina	United States	27295
14	Pfizer Investigational Site	Mount Airy	North Carolina	United States	27030
15	Pfizer Investigational Site	North Wilkesboro	North Carolina	United States	28659
16	Pfizer Investigational Site	Winston-Salem	North Carolina	United States	27103
17	Pfizer Investigational Site	Beaverton	Oregon	United States	97006
18	Pfizer Investigational Site	Gresham	Oregon	United States	97030
19	Pfizer Investigational Site	Portland	Oregon	United States	97210
20	Pfizer Investigational Site	Portland	Oregon	United States	97239
21	Pfizer Investigational Site	Tualatin	Oregon	United States	97062
22	Pfizer Investigational Site	West Reading	Pennsylvania	United States	19611
23	Pfizer Investigational Site	Christiansburg	Virginia	United States	24074
24	Pfizer Investigational Site	Low Moor	Virginia	United States	24457
25	Pfizer Investigational Site	Roanoke	Virginia	United States	24014
26	Pfizer Investigational Site	Salem	Virginia	United States	24153
27	Pfizer Investigational Site	Wytheville	Virginia	United States	24382
28	Pfizer Investigational Site	Everett	Washington	United States	98201
29	Pfizer Investigational Site	Federal Way	Washington	United States	98003
30	Pfizer Investigational Site	Gig Harbor	Washington	United States	98332
31	Pfizer Investigational Site	Kennewick	Washington	United States	99336
32	Pfizer Investigational Site	Lakewood	Washington	United States	98499
33	Pfizer Investigational Site	Puyallup	Washington	United States	98372
34	Pfizer Investigational Site	Tacoma	Washington	United States	98405
35	Pfizer Investigational Site	Oshawa	Ontario	Canada	L1G 2B9
36	Pfizer Investigational Site	Sudbury	Ontario	Canada	P3E 5J1
37	Pfizer Investigational Site	Levis	Quebec	Canada	G6V 3Z1
38	Pfizer Investigational Site	Montreal	Quebec	Canada	H4J 1C5
39	Pfizer Investigational Site	Budapest		Hungary	1125
40	Pfizer Investigational Site	Debrecen		Hungary	4032
41	Pfizer Investigational Site	Deszk		Hungary	6772
42	Pfizer Investigational Site	Farkasgyepu		Hungary	8582
43	Pfizer Investigational Site	Torokbalint		Hungary	2045
44	Pfizer Investigational Site	Barcelona		Spain	08025
45	Pfizer Investigational Site	Barcelona		Spain	08036
46	Pfizer Investigational Site	Las Palmas de Gran Canaria		Spain	35016
47	Pfizer Investigational Site	Madrid		Spain	28041
48	Pfizer Investigational Site	Malaga		Spain	29010
49	Pfizer Investigational Site	Sevilla		Spain	41009
50	Pfizer Investigational Site	Sevilla		Spain	41013
51	Pfizer Investigational Site	Valencia		Spain	46026

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00977561
• Other Study ID Numbers: A4021032
• First Posted: Sep 15, 2009
• Last Update Posted: Feb 25, 2013
• Last Verified: Jan 1, 2013

• Keywords provided by Pfizer: Small Cell Lung Cancer; Extensive stage disease; SCLC; IGF-1R inhibitor
• Additional relevant MeSH terms: Lung Neoplasms; Small Cell Lung Carcinoma; Cisplatin; Carboplatin; Etoposide; Etoposide phosphate

Study Results

Participant Flow

Arm/Group Title	Figitumumab + Cisplatin or Carboplatin + Etoposide	Cisplatin or Carboplatin + Etoposide
Arm/Group Description	Figitumumab 20 milligram/kilogram (mg/kg) administered intravenously (IV) over 1 hour on Day 2 of Cycle 1 and on Day 1 of subsequent cycles (up to 17 cycles in the absence of further disease progression or intolerable toxicity). Cisplatin 75 milligram/square meter (mg/m^2) IV over 1 hour or carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 5 milligram/milliliter*minute (mg/mL*min) IV over 15-60 minutes on Day 1 (up to 6 cycles) followed by etoposide 100 mg/m^2 IV over 1 hour on Days 1, 2 and 3 of each cycle (up to 6 cycles or until progression or intolerable toxicity). Each cycle was 21 days cycle.	Cisplatin 75 mg/m^2 IV over 1 hour or carboplatin at a dose to attain the target AUC of 5 mg/mL*min IV over 15-60 minutes on Day 1 (up to 6 cycles) followed by etoposide 100 mg/m^2 IV over 1 hour on Days 1, 2 and 3 of each cycle (up to 6 cycles or until progression or intolerable toxicity). Each cycle was 21 days cycle.
Period Title: Overall Study
STARTED	5	4
COMPLETED	0	0
NOT COMPLETED	5	4

Baseline Characteristics

Arm/Group Title	Figitumumab + Cisplatin or Carboplatin + Etoposide	Cisplatin or Carboplatin + Etoposide	Total
Arm/Group Description	Figitumumab 20 mg/kg administered IV over 1 hour on Day 2 of Cycle 1 and on Day 1 of subsequent cycles (up to 17 cycles in the absence of further disease progression or intolerable toxicity). Cisplatin 75 mg/m^2 IV over 1 hour or carboplatin at a dose to attain the target AUC of 5 mg/mL*min IV over 15-60 minutes on Day 1 (up to 6 cycles) followed by etoposide 100 mg/m^2 IV over 1 hour on Day 1, 2 and 3 of each cycle (up to 6 cycles or until progression or intolerable toxicity). Each cycle was 21 days cycle.	Cisplatin 75 mg/m^2 IV over 1 hour or carboplatin at a dose to attain the target AUC of 5 mg/mL*min IV over 15-60 minutes on Day 1 (up to 6 cycles) followed by etoposide 100 mg/m^2 IV over 1 hour on Days 1, 2 and 3 of each cycle (up to 6 cycles or until progression or intolerable toxicity). Each cycle was 21 days cycle.	Total of all reporting groups
Overall Participants	5	4	9
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.4 (4.4)	53.8 (11.0)	57.4 (8.2)
Sex: Female, Male (Count of Participants)
Female	5 100%	1 25%	6 66.7%
Male	0 0%	3 75%	3 33.3%

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival (PFS)
Description	Median time from the first dose of study treatment to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first. PFS time (days) = [event (progression or death) date or censor date - date of randomization + 1].
Time Frame	Baseline, every 2nd cycle (between Day 15-21, 1 cycle = 21 days) starting with Cycle 2 until disease progression, at the end of treatment visit (if more than 28 days have passed since last evaluation); and every 6 weeks until disease progression

Outcome Measure Data

Analysis Population Description

No analysis of progression-free survival was performed as the study was terminated prematurely due to low participants enrollment and the halting of the figitumumab development program. As a result, the only endpoint analyzed for the study was safety and tolerability of figitumumab ± cisplatin (or carboplatin) and etoposide.

Arm/Group Title	Figitumumab + Cisplatin or Carboplatin + Etoposide	Cisplatin or Carboplatin + Etoposide
Arm/Group Description	Figitumumab 20 mg/kg administered IV over 1 hour on Day 2 of Cycle 1 and on Day 1 of subsequent cycles (up to 17 cycles in the absence of further disease progression or intolerable toxicity). Cisplatin 75 mg/m^2 IV over 1 hour or carboplatin at a dose to attain the target AUC of 5 mg/mL*min IV over 15-60 minutes on Day 1 (up to 6 cycles) followed by etoposide 100 mg/m^2 IV over 1 hour on Days 1, 2 and 3 of each cycle (up to 6 cycles or until progression or intolerable toxicity). Each cycle was 21 days cycle.	Cisplatin 75 mg/m^2 IV over 1 hour or carboplatin at a dose to attain the target AUC of 5 mg/mL*min IV over 15-60 minutes on Day 1 (up to 6 cycles) followed by etoposide 100 mg/m^2 IV over 1 hour on Days 1, 2 and 3 of each cycle (up to 6 cycles or until progression or intolerable toxicity). Each cycle was 21 days cycle.
Measure Participants	0	0

2. Secondary Outcome

Title	Number of Participants With Objective Response
Description	Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST.
Time Frame	Baseline, every 2nd cycle (between Day 15-21, 1 cycle = 21 days) starting with Cycle 2 until disease progression, at the end of treatment visit (if more than 28 days have passed since last evaluation); and every 6 weeks until disease progression

Outcome Measure Data

Analysis Population Description

No analysis of objective response was performed as the study was terminated prematurely due to low participants enrollment and the halting of the figitumumab development program. As a result, the only endpoint analyzed for the study was safety and tolerability of figitumumab ± cisplatin (or carboplatin) and etoposide.

Arm/Group Title	Figitumumab + Cisplatin or Carboplatin + Etoposide	Cisplatin or Carboplatin + Etoposide
Arm/Group Description	Figitumumab 20 mg/kg administered IV over 1 hour on Day 2 of Cycle 1 and on Day 1 of subsequent cycles (up to 17 cycles in the absence of further disease progression or intolerable toxicity). Cisplatin 75 mg/m^2 IV over 1 hour or carboplatin at a dose to attain the target AUC of 5 mg/mL*min IV over 15-60 minutes on Day 1 (up to 6 cycles) followed by etoposide 100 mg/m^2 IV over 1 hour on Days 1, 2 and 3 of each cycle (up to 6 cycles or until progression or intolerable toxicity). Each cycle was 21 days cycle.	Cisplatin 75 mg/m^2 IV over 1 hour or carboplatin at a dose to attain the target AUC of 5 mg/mL*min IV over 15-60 minutes on Day 1 (up to 6 cycles) followed by etoposide 100 mg/m^2 IV over 1 hour on Days 1, 2 and 3 of each cycle (up to 6 cycles or until progression or intolerable toxicity). Each cycle was 21 days cycle.
Measure Participants	0	0

3. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall survival was the duration from enrollment to death due to any cause. For participants who are alive, overall survival was censored at the last contact. Survival time (days) = [death date (last known alive date) - date of randomization +1].
Time Frame	Every 3 months until death or 12 months from the date the last participant was randomized

Outcome Measure Data

Analysis Population Description

No analysis of overall survival was performed as the study was terminated prematurely due to low participants enrollment and the halting of the figitumumab development program. As a result, the only endpoint analyzed for the study was safety and tolerability of figitumumab ± cisplatin (or carboplatin) and etoposide.

Arm/Group Title	Figitumumab + Cisplatin or Carboplatin + Etoposide	Cisplatin or Carboplatin + Etoposide
Arm/Group Description	Figitumumab 20 mg/kg administered IV over 1 hour on Day 2 of Cycle 1 and on Day 1 of subsequent cycles (up to 17 cycles in the absence of further disease progression or intolerable toxicity). Cisplatin 75 mg/m^2 IV over 1 hour or carboplatin at a dose to attain the target AUC of 5 mg/mL*min IV over 15-60 minutes on Day 1 (up to 6 cycles) followed by etoposide 100 mg/m^2 IV over 1 hour on Days 1, 2 and 3 of each cycle (up to 6 cycles or until progression or intolerable toxicity). Each cycle was 21 days cycle.	Cisplatin 75 mg/m^2 IV over 1 hour or carboplatin at a dose to attain the target AUC of 5 mg/mL*min IV over 15-60 minutes on Day 1 (up to 6 cycles) followed by etoposide 100 mg/m^2 IV over 1 hour on Days 1, 2 and 3 of each cycle (up to 6 cycles or until progression or intolerable toxicity). Each cycle was 21 days cycle.
Measure Participants	0	0

4. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	AEs are any untoward, undesired, or unplanned event in the form of signs, symptoms, disease, or laboratory or physiologic observations occurring in a person given study treatment. The event does not need to be causally related to the study treatment. SAEs include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly or birth defect in the offspring of a study subject.
Time Frame	Baseline up to follow-up (90 days post dose)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of any agent of the combination were included in the safety analysis.

Arm/Group Title	Figitumumab + Cisplatin or Carboplatin + Etoposide	Cisplatin or Carboplatin + Etoposide
Arm/Group Description	Figitumumab 20 mg/kg administered IV over 1 hour on Day 2 of Cycle 1 and on Day 1 of subsequent cycles (up to 17 cycles in the absence of further disease progression or intolerable toxicity). Cisplatin 75 mg/m^2 IV over 1 hour or carboplatin at a dose to attain the target AUC of 5 mg/mL*min IV over 15-60 minutes on Day 1 (up to 6 cycles) followed by etoposide 100 mg/m^2 IV over 1 hour on Days 1, 2 and 3 of each cycle (up to 6 cycles or until progression or intolerable toxicity). Each cycle was 21 days cycle.	Cisplatin 75 mg/m^2 IV over 1 hour or carboplatin at a dose to attain the target AUC of 5 mg/mL*min IV over 15-60 minutes on Day 1 (up to 6 cycles) followed by etoposide 100 mg/m^2 IV over 1 hour on Days 1, 2 and 3 of each cycle (up to 6 cycles or until progression or intolerable toxicity). Each cycle was 21 days cycle.
Measure Participants	5	4
Adverse Events	5 100%	4 100%
Serious Adverse Events	4 80%	2 50%

5. Secondary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of Figitumumab
Time Frame	Cycle 1, Day 2; Day 1 of Cycles 2, 4, 5, 6, 10 and 15; Day 28 and Day 90 post last figitumumab dose

Outcome Measure Data

Analysis Population Description

No analysis of Cmax for figitumumab was performed as the study was terminated prematurely due to low participants enrollment and the halting of the figitumumab development program. As a result, the only endpoint analyzed for the study was safety and tolerability of figitumumab ± cisplatin (or carboplatin) and etoposide.

Arm/Group Title	Figitumumab+ Cisplatin (or Carboplatin) + Etoposide
Arm/Group Description	Figitumumab 20 mg/kg administered IV over 1 hour on Day 2 of Cycle 1 and on Day 1 of subsequent cycles (up to 17 cycles in the absence of further disease progression or intolerable toxicity). Cisplatin 75 mg/m^2 IV over 1 hour or carboplatin at a dose to attain the target AUC of 5 mg/mL*min IV over 15-60 minutes on Day 1 (up to 6 cycles) followed by etoposide 100 mg/m^2 IV over 1 hour on Days 1, 2 and 3 of each cycle (up to 6 cycles or until progression or intolerable toxicity). Each cycle was 21 days cycle.
Measure Participants	0

6. Secondary Outcome

Title	Minimum Observed Plasma Trough Concentration (Cmin) of Figitumumab
Time Frame	Cycle 1, Day 2; Day 1 of Cycles 2, 4, 5, 6, 10 and 15; Day 28 and Day 90 post last figitumumab dose

Outcome Measure Data

Analysis Population Description

No analysis of Cmin for figitumumab was performed as the study was terminated prematurely due to low participants enrollment and the halting of the figitumumab development program. As a result, the only endpoint analyzed for the study was safety and tolerability of figitumumab ± cisplatin (or carboplatin) and etoposide.

Arm/Group Title	Figitumumab + Cisplatin or Carboplatin + Etoposide
Arm/Group Description	Figitumumab 20 mg/kg administered IV over 1 hour on Day 2 of Cycle 1 and on Day 1 of subsequent cycles (up to 17 cycles in the absence of further disease progression or intolerable toxicity). Cisplatin 75 mg/m^2 IV over 1 hour or carboplatin at a dose to attain the target AUC of 5 mg/mL*min IV over 15-60 minutes on Day 1 (up to 6 cycles) followed by etoposide 100 mg/m^2 IV over 1 hour on Days 1, 2 and 3 of each cycle (up to 6 cycles or until progression or intolerable toxicity). Each cycle was 21 days cycle.
Measure Participants	0

7. Secondary Outcome

Title	Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Etoposide
Description	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
Time Frame	Cycles 1 and 2, Day 1 and Day 2 (within 3 hours prior to Day 1 etoposide infusion; 1, 1.5, 2, 3, 6, and 24 hours post Day 1 etoposide infusion); Cycles 4 and 5, Day 2: 24 hours post Day 1 etoposide infusion

Outcome Measure Data

Analysis Population Description

No analysis of pharmacokinetics (PK) parameters for etoposide was performed as the study was terminated prematurely due to low participants enrollment and the halting of the figitumumab development program. As a result, the only endpoint analyzed for the study was safety and tolerability of figitumumab ± cisplatin (or carboplatin) and etoposide.

Arm/Group Title	Figitumumab + Cisplatin or Carboplatin + Etoposide
Arm/Group Description	Figitumumab 20 mg/kg administered IV over 1 hour on Day 2 of Cycle 1 and on Day 1 of subsequent cycles (up to 17 cycles in the absence of further disease progression or intolerable toxicity). Cisplatin 75 mg/m^2 IV over 1 hour or carboplatin at a dose to attain the target AUC of 5 mg/mL*min IV over 15-60 minutes on Day 1 (up to 6 cycles) followed by etoposide 100 mg/m^2 IV over 1 hour on Days 1, 2 and 3 of each cycle (up to 6 cycles or until progression or intolerable toxicity). Each cycle was 21 days cycle.
Measure Participants	0

8. Secondary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of Etoposide
Time Frame	Cycles 1 and 2, Day 1 and Day 2 (within 3 hours prior to Day 1 etoposide infusion; 1, 1.5, 2, 3, 6, and 24 hours post Day 1 etoposide infusion); Cycles 4 and 5, Day 2: 24 hours post Day 1 etoposide infusion

Outcome Measure Data

Analysis Population Description

No analysis of PK parameters for etoposide was performed as the study was terminated prematurely due to low participants enrollment and the halting of the figitumumab development program. As a result, the only endpoint analyzed for the study was safety and tolerability of figitumumab ± cisplatin (or carboplatin) and etoposide.

Arm/Group Title	Figitumumab + Cisplatin or Carboplatin + Etoposide
Arm/Group Description	Figitumumab 20 mg/kg administered IV over 1 hour on Day 2 of Cycle 1 and on Day 1 of subsequent cycles (up to 17 cycles in the absence of further disease progression or intolerable toxicity). Cisplatin 75 mg/m^2 IV over 1 hour or carboplatin at a dose to attain the target AUC of 5 mg/mL*min IV over 15-60 minutes on Day 1 (up to 6 cycles) followed by etoposide 100 mg/m^2 IV over 1 hour on Days 1, 2 and 3 of each cycle (up to 6 cycles or until progression or intolerable toxicity). Each cycle was 21 days cycle.
Measure Participants	0

9. Secondary Outcome

Title	Percentage of Participants Reporting Positive Anti-Drug Antibodies (ADA) Response for Figitumumab
Description	Percentage of participants with positive total or neutralizing anti-drug antibody (ADA) for figitumumab
Time Frame	Day 2 of Cycle 1 (or Day 1 of the initial cycle starting single agent figitumumab); Day 1 of Cycles 2 and 4; Day 28 and Day 90 post last figitumumab dose

Outcome Measure Data

Analysis Population Description

No analysis of ADA response was performed as the study was terminated prematurely due to low participants enrollment and the halting of the figitumumab development program. As a result, the only endpoint analyzed for the study was safety and tolerability of figitumumab ± cisplatin (or carboplatin) and etoposide.

Arm/Group Title	Figitumumab + Cisplatin or Carboplatin + Etoposide
Arm/Group Description	Participants who received figitumumab, whether figitumumab (20 mg/kg, IV over 1 hour on Day 2 of Cycle 1 and on Day 1 of subsequent cycles) was given in combination with cisplatin (75 mg/m^2 IV over 1 hour on Day 1 of each cycle) or carboplatin (AUC of 5 mg/mL*min IV over 15-60 minutes on Day 1 of each cycle) followed by etoposide (100 mg/m^2 IV over 1 hour on Days 1, 2 and 3 of each cycle) from the beginning or figitumumab was given as a single agent after documented disease progression with cisplatin (or carboplatin) and etoposide. When given as a single agent, figitumumab was administered as IV infusion on Days 1 and 2 of the initial cycle and on Day 1 of subsequent cycles, up to 17 cycles in the absence of further disease progression or intolerable toxicity. Each cycle was 21 days cycle.
Measure Participants	0

10. Secondary Outcome

Title	Cancer Dyspnea Scale (CDS) Score
Description	The Cancer Dyspnea Scale consists of 12 questions that assess 3 domains of dyspnea (sense of effort, anxiety and discomfort) related to lung cancer. The questions are answered on 5-point Likert scale ranging from 1 to 5 (1 "Not at All" to 5 "Very Much").
Time Frame	Day 1 of every cycle (up to 17 cycles), at the end of treatment visit (28 days post last dose); then every 6 weeks until disease progression

Outcome Measure Data

Analysis Population Description

No analysis for cancer dyspnea scale score was performed as the study was terminated prematurely due to low participants enrollment and the halting of the figitumumab development program. As a result, the only endpoint analyzed for the study was safety and tolerability of figitumumab ± cisplatin (or carboplatin) and etoposide.

Arm/Group Title	Figitumumab + Cisplatin or Carboplatin + Etoposide	Cisplatin or Carboplatin + Etoposide
Arm/Group Description	Figitumumab 20 mg/kg administered IV over 1 hour on Day 2 of Cycle 1 and on Day 1 of subsequent cycles (up to 17 cycles in the absence of further disease progression or intolerable toxicity). Cisplatin 75 mg/m^2 IV over 1 hour or carboplatin at a dose to attain the target AUC of 5 mg/mL*min IV over 15-60 minutes on Day 1 (up to 6 cycles) followed by etoposide 100 mg/m^2 IV over 1 hour on Days 1, 2 and 3 of each cycle (up to 6 cycles or until progression or intolerable toxicity). Each cycle was 21 days cycle.	Cisplatin 75 mg/m^2 IV over 1 hour or carboplatin at a dose to attain the target AUC of 5 mg/mL*min IV over 15-60 minutes on Day 1 (up to 6 cycles) followed by etoposide 100 mg/m^2 IV over 1 hour on Days 1, 2 and 3 of each cycle (up to 6 cycles or until progression or intolerable toxicity). Each cycle was 21 days cycle.
Measure Participants	0	0

11. Secondary Outcome

Title	Numeric Rating Scale (NRS) Score
Description	The Numeric Rating Scale (NRS) is a 1-item self-reported questionnaire designed to assess "worst pain" severity. Overall scores range from 0 to 10, with low scores representing a lower level of pain.
Time Frame	Day 1 of every cycle (up to 17 cycles), at the end of treatment visit (28 days post last dose); then every 6 weeks until disease progression

Outcome Measure Data

Analysis Population Description

No analysis for NRS score was performed as the study was terminated prematurely due to low participants enrollment and the halting of the figitumumab development program. As a result, the only endpoint analyzed for the study was safety and tolerability of figitumumab ± cisplatin (or carboplatin) and etoposide.

Arm/Group Title	Figitumumab + Cisplatin or Carboplatin + Etoposide	Cisplatin or Carboplatin + Etoposide
Arm/Group Description	Figitumumab 20 mg/kg administered IV over 1 hour on Day 2 of Cycle 1 and on Day 1 of subsequent cycles (up to 17 cycles in the absence of further disease progression or intolerable toxicity). Cisplatin 75 mg/m^2 IV over 1 hour or carboplatin at a dose to attain the target AUC of 5 mg/mL*min IV over 15-60 minutes on Day 1 (up to 6 cycles) followed by etoposide 100 mg/m^2 IV over 1 hour on Days 1, 2 and 3 of each cycle (up to 6 cycles or until progression or intolerable toxicity). Each cycle was 21 days cycle.	Cisplatin 75 mg/m^2 IV over 1 hour or carboplatin at a dose to attain the target AUC of 5 mg/mL*min IV over 15-60 minutes on Day 1 (up to 6 cycles) followed by etoposide 100 mg/m^2 IV over 1 hour on Days 1, 2 and 3 of each cycle (up to 6 cycles or until progression or intolerable toxicity). Each cycle was 21 days cycle.
Measure Participants	0	0

12. Secondary Outcome

Title	Pre-treatment Levels of Tumor Biomarkers Involved in Insulin-Like Growth Factor 1 (IGF-I) Signaling Pathway
Time Frame	Baseline prior to dosing

Outcome Measure Data

Analysis Population Description

No analysis of tumor biomarkers was performed as the study was terminated prematurely due to low participants enrollment and the halting of the figitumumab development program. As a result, the only endpoint analyzed for the study was safety and tolerability of figitumumab ± cisplatin (or carboplatin) and etoposide.

Arm/Group Title	Figitumumab + Cisplatin or Carboplatin + Etoposide	Cisplatin or Carboplatin + Etoposide
Arm/Group Description	Figitumumab 20 mg/kg administered IV over 1 hour on Day 2 of Cycle 1 and on Day 1 of subsequent cycles (up to 17 cycles in the absence of further disease progression or intolerable toxicity). Cisplatin 75 mg/m^2 IV over 1 hour or carboplatin at a dose to attain the target AUC of 5 mg/mL*min IV over 15-60 minutes on Day 1 (up to 6 cycles) followed by etoposide 100 mg/m^2 IV over 1 hour on Days 1, 2 and 3 of each cycle (up to 6 cycles or until progression or intolerable toxicity). Each cycle was 21 days cycle.	Cisplatin 75 mg/m^2 IV over 1 hour or carboplatin at a dose to attain the target AUC of 5 mg/mL*min IV over 15-60 minutes on Day 1 (up to 6 cycles) followed by etoposide 100 mg/m^2 IV over 1 hour on Days 1, 2 and 3 of each cycle (up to 6 cycles or until progression or intolerable toxicity). Each cycle was 21 days cycle.
Measure Participants	0	0

13. Secondary Outcome

Title	Levels of Serum Circulating Insulin-like Growth Factor (IGF) Pathway Related Markers
Time Frame	Baseline (Cycle 1, Day 1 prior to dosing), Cycle 4 (Day 1), at the end of treatment visit (28 days post last figitumumab dose)

Outcome Measure Data

Analysis Population Description

No analysis for serum circulating IGF pathway related markers was performed as the study was terminated prematurely due to low participants enrollment and the halting of the figitumumab development program. As a result, the only endpoint analyzed for the study was safety and tolerability of figitumumab ± cisplatin (or carboplatin) and etoposide.

Arm/Group Title	Figitumumab + Cisplatin or Carboplatin + Etoposide	Cisplatin or Carboplatin + Etoposide
Arm/Group Description	Figitumumab 20 mg/kg administered IV over 1 hour on Day 2 of Cycle 1 and on Day 1 of subsequent cycles (up to 17 cycles in the absence of further disease progression or intolerable toxicity). Cisplatin 75 mg/m^2 IV over 1 hour or carboplatin at a dose to attain the target AUC of 5 mg/mL*min IV over 15-60 minutes on Day 1 (up to 6 cycles) followed by etoposide 100 mg/m^2 IV over 1 hour on Days 1, 2 and 3 of each cycle (up to 6 cycles or until progression or intolerable toxicity). Each cycle was 21 days cycle.	Cisplatin 75 mg/m^2 IV over 1 hour or carboplatin at a dose to attain the target AUC of 5 mg/mL*min IV over 15-60 minutes on Day 1 (up to 6 cycles) followed by etoposide 100 mg/m^2 IV over 1 hour on Days 1, 2 and 3 of each cycle (up to 6 cycles or until progression or intolerable toxicity). Each cycle was 21 days cycle.
Measure Participants	0	0

14. Secondary Outcome

Title	Number of Total Circulating Tumor-Related Cells (CTCs) and Insulin-Like Growth Factor 1 Receptor (IGF-IR)-Expressing CTCs
Description	Pre-treatment and post-treatment counts of total and IGF-IR-positive CTCs
Time Frame	Baseline (Cycle 1, Day 1), Cycle 4 (Day 1) and at the end of treatment visit (28 days post last figitumumab dose)

Outcome Measure Data

Analysis Population Description

No analysis of total CTCs and IGF-IR-expressing CTCs was performed as the study was terminated prematurely due to low participants enrollment and the halting of the figitumumab development program. As a result, the only endpoint analyzed for the study was safety and tolerability of figitumumab ± cisplatin (or carboplatin) and etoposide.

Arm/Group Title	Figitumumab + Cisplatin or Carboplatin + Etoposide	Cisplatin or Carboplatin + Etoposide
Arm/Group Description	Figitumumab 20 mg/kg administered IV over 1 hour on Day 2 of Cycle 1 and on Day 1 of subsequent cycles (up to 17 cycles in the absence of further disease progression or intolerable toxicity). Cisplatin 75 mg/m^2 IV over 1 hour or carboplatin at a dose to attain the target AUC of 5 mg/mL*min IV over 15-60 minutes on Day 1 (up to 6 cycles) followed by etoposide 100 mg/m^2 IV over 1 hour on Days 1, 2 and 3 of each cycle (up to 6 cycles or until progression or intolerable toxicity). Each cycle was 21 days cycle.	Cisplatin 75 mg/m^2 IV over 1 hour or carboplatin at a dose to attain the target AUC of 5 mg/mL*min IV over 15-60 minutes on Day 1 (up to 6 cycles) followed by etoposide 100 mg/m^2 IV over 1 hour on Days 1, 2 and 3 of each cycle (up to 6 cycles or until progression or intolerable toxicity). Each cycle was 21 days cycle.
Measure Participants	0	0

Adverse Events

Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Arm/Group Title	Figitumumab + Cisplatin or Carboplatin + Etoposide		Cisplatin or Carboplatin + Etoposide
Arm/Group Description	Figitumumab 20 mg/kg administered IV over 1 hour on Day 2 of Cycle 1 and on Day 1 of subsequent cycles (up to 17 cycles in the absence of further disease progression or intolerable toxicity). Cisplatin 75 mg/m^2 IV over 1 hour or carboplatin at a dose to attain the target AUC of 5 mg/mL*min IV over 15-60 minutes on Day 1 (up to 6 cycles) followed by etoposide 100 mg/m^2 IV over 1 hour on Days 1, 2 and 3 of each cycle (up to 6 cycles or until progression or intolerable toxicity). Each cycle was 21 days cycle.		Cisplatin 75 mg/m^2 IV over 1 hour or carboplatin at a dose to attain the target AUC of 5 mg/mL*min IV over 15-60 minutes on Day 1 (up to 6 cycles) followed by etoposide 100 mg/m^2 IV over 1 hour on Days 1, 2 and 3 of each cycle (up to 6 cycles or until progression or intolerable toxicity). Each cycle was 21 days cycle.
All Cause Mortality
	Figitumumab + Cisplatin or Carboplatin + Etoposide		Cisplatin or Carboplatin + Etoposide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Figitumumab + Cisplatin or Carboplatin + Etoposide		Cisplatin or Carboplatin + Etoposide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/5 (80%)		2/4 (50%)
Blood and lymphatic system disorders
Anaemia	0/5 (0%)		1/4 (25%)
Febrile neutropenia	1/5 (20%)		0/4 (0%)
Cardiac disorders
Myocardial infarction	1/5 (20%)		0/4 (0%)
Gastrointestinal disorders
Diarrhoea	1/5 (20%)		0/4 (0%)
Vomiting	1/5 (20%)		0/4 (0%)
General disorders
Disease progression	1/5 (20%)		1/4 (25%)
Metabolism and nutrition disorders
Dehydration	1/5 (20%)		0/4 (0%)
Psychiatric disorders
Psychotic disorder	1/5 (20%)		0/4 (0%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/5 (20%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	Figitumumab + Cisplatin or Carboplatin + Etoposide		Cisplatin or Carboplatin + Etoposide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/5 (100%)		4/4 (100%)
Blood and lymphatic system disorders
Anaemia	0/5 (0%)		2/4 (50%)
Granulocytopenia	1/5 (20%)		0/4 (0%)
Leukopenia	2/5 (40%)		0/4 (0%)
Neutropenia	4/5 (80%)		4/4 (100%)
Thrombocytopenia	1/5 (20%)		1/4 (25%)
Ear and labyrinth disorders
Deafness	1/5 (20%)		0/4 (0%)
Tinnitus	0/5 (0%)		1/4 (25%)
Endocrine disorders
Hypothyroidism	1/5 (20%)		0/4 (0%)
Eye disorders
Ocular hyperaemia	1/5 (20%)		0/4 (0%)
Visual acuity reduced	1/5 (20%)		0/4 (0%)
Gastrointestinal disorders
Abdominal discomfort	1/5 (20%)		0/4 (0%)
Constipation	1/5 (20%)		2/4 (50%)
Diarrhoea	1/5 (20%)		1/4 (25%)
Dry mouth	0/5 (0%)		1/4 (25%)
Gastrooesophageal reflux disease	0/5 (0%)		1/4 (25%)
Gingival bleeding	1/5 (20%)		0/4 (0%)
Gingivitis	1/5 (20%)		0/4 (0%)
Nausea	3/5 (60%)		4/4 (100%)
Stomatitis	2/5 (40%)		0/4 (0%)
Vomiting	1/5 (20%)		2/4 (50%)
General disorders
Asthenia	1/5 (20%)		2/4 (50%)
Fatigue	2/5 (40%)		0/4 (0%)
Feeling cold	1/5 (20%)		0/4 (0%)
Influenza like illness	0/5 (0%)		1/4 (25%)
Infusion site extravasation	1/5 (20%)		0/4 (0%)
Mucosal inflammation	0/5 (0%)		1/4 (25%)
Non-cardiac chest pain	0/5 (0%)		1/4 (25%)
Oedema peripheral	1/5 (20%)		0/4 (0%)
Pyrexia	1/5 (20%)		0/4 (0%)
Infections and infestations
Candidiasis	0/5 (0%)		2/4 (50%)
Otitis media	0/5 (0%)		1/4 (25%)
Urinary tract infection	2/5 (40%)		0/4 (0%)
Investigations
Alanine aminotransferase increased	1/5 (20%)		0/4 (0%)
Aspartate aminotransferase increased	1/5 (20%)		0/4 (0%)
Blood alkaline phosphatase increased	1/5 (20%)		0/4 (0%)
Blood creatinine increased	1/5 (20%)		0/4 (0%)
Creatinine renal clearance decreased	1/5 (20%)		0/4 (0%)
Gamma-glutamyltransferase increased	2/5 (40%)		0/4 (0%)
Haemoglobin decreased	2/5 (40%)		0/4 (0%)
Weight decreased	2/5 (40%)		1/4 (25%)
Metabolism and nutrition disorders
Cachexia	0/5 (0%)		1/4 (25%)
Decreased appetite	2/5 (40%)		1/4 (25%)
Dehydration	0/5 (0%)		2/4 (50%)
Hyperglycaemia	1/5 (20%)		0/4 (0%)
Hyperuricaemia	1/5 (20%)		0/4 (0%)
Hypocalcaemia	1/5 (20%)		0/4 (0%)
Hypokalaemia	0/5 (0%)		1/4 (25%)
Hypomagnesaemia	1/5 (20%)		1/4 (25%)
Hyponatraemia	1/5 (20%)		1/4 (25%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/5 (0%)		1/4 (25%)
Back pain	0/5 (0%)		3/4 (75%)
Bone pain	0/5 (0%)		1/4 (25%)
Mobility decreased	1/5 (20%)		0/4 (0%)
Musculoskeletal pain	0/5 (0%)		1/4 (25%)
Neck pain	0/5 (0%)		1/4 (25%)
Pain in extremity	1/5 (20%)		1/4 (25%)
Nervous system disorders
Balance disorder	0/5 (0%)		1/4 (25%)
Convulsion	0/5 (0%)		1/4 (25%)
Dizziness	0/5 (0%)		1/4 (25%)
Dysgeusia	0/5 (0%)		1/4 (25%)
Headache	0/5 (0%)		1/4 (25%)
Neuropathy peripheral	1/5 (20%)		1/4 (25%)
Peripheral sensory neuropathy	1/5 (20%)		0/4 (0%)
Somnolence	2/5 (40%)		0/4 (0%)
Psychiatric disorders
Confusional state	1/5 (20%)		0/4 (0%)
Insomnia	2/5 (40%)		1/4 (25%)
Renal and urinary disorders
Polyuria	1/5 (20%)		0/4 (0%)
Reproductive system and breast disorders
Breast pain	1/5 (20%)		0/4 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	1/5 (20%)		0/4 (0%)
Dyspnoea	0/5 (0%)		1/4 (25%)
Epistaxis	2/5 (40%)		0/4 (0%)
Hiccups	1/5 (20%)		0/4 (0%)
Hypoxia	0/5 (0%)		1/4 (25%)
Nasal ulcer	1/5 (20%)		0/4 (0%)
Pharyngeal disorder	1/5 (20%)		0/4 (0%)
Sneezing	1/5 (20%)		0/4 (0%)
Skin and subcutaneous tissue disorders
Alopecia	3/5 (60%)		2/4 (50%)
Dermatitis acneiform	0/5 (0%)		1/4 (25%)
Dry skin	1/5 (20%)		0/4 (0%)
Nail disorder	1/5 (20%)		0/4 (0%)
Pruritus	1/5 (20%)		0/4 (0%)
Rash papular	1/5 (20%)		0/4 (0%)
Vascular disorders
Deep vein thrombosis	1/5 (20%)		0/4 (0%)
Hypotension	0/5 (0%)		1/4 (25%)
Pallor	1/5 (20%)		1/4 (25%)

Limitations/Caveats

The study was terminated prematurely due to low participants enrollment and the halting of the figitumumab development program. The only endpoint analyzed was safety and tolerability of figitumumab ± cisplatin (or carboplatin) and etoposide.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.