Chemotherapy With or Without Bevacizumab in Patients With Completely Resected Stage IB-IIIA Non-small Cell Lung Cancer

Study Type:	Interventional
Study Design:	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Conditions:	Stage IB Non-Small Cell Lung Carcinoma; Stage IIA Non-Small Cell Lung Carcinoma; Stage IIB Non-Small Cell Lung Carcinoma; Stage IIIA Non-small Cell Lung Cancer
Interventions:	Biological: Bevacizumab; Drug: Cisplatin; Drug: Docetaxel; Drug: Gemcitabine Hydrochloride; Drug: Pemetrexed Disodium; Drug: Vinorelbine

  Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Patients were recruited between June 1, 2007 and September 20, 2013 from ECOG-ACRIN, SWOG, RTOG, CALGB, NCCTG, NCIC-CTG, NSABP, ACOSOG, and CTSU sites.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups

	Description
Arm I (Chemotherapy)	Patients receive one of the following. For all, treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. REGIMEN 1: Vinorelbine ditartrate 30 mg/m2 intravenously (IV) on days 1 and 8, cisplatin 75 mg/m2 IV over 60 minutes on day 1 REGIMEN 2: Docetaxel 75 mg/m2 IV and cisplastin 75 mg/m2 IV on day 1 REGIMEN 3: Gemcitabine hydrochloride 1200 mg/m2 IV on days 1 and 8, cisplatin 75 mg/m2 IV on day 1 REGIMEN 4 (non-squamous histology only): Pemetrexed disodium 500mg/m2 IV and cisplatin 75 mg/m2 IV on day 1 Cisplatin: Given IV Docetaxel: Given IV Gemcitabine Hydrochloride: Given IV Pemetrexed Disodium: Given IV Vinorelbine: Given IV
Arm II (Chemotherapy, Bevacizumab)	Patients receive chemotherapy as in Arm I. Patients also receive bevacizumab IV over 30-90 minutes on day 1. Treatment with bevacizumab repeats every 21 days for up to 1 year. Bevacizumab: Given IV Cisplatin: Given IV Docetaxel: Given IV Gemcitabine Hydrochloride: Given IV Pemetrexed Disodium: Given IV Vinorelbine: Given IV

Participant Flow:   Overall Study

	Arm I (Chemotherapy)	Arm II (Chemotherapy, Bevacizumab)
STARTED	749	752
Started Assigned Therapy	737	735
COMPLETED	599	269
NOT COMPLETED	150	483
Adverse Event	62	203
Progression	7	35
Withdrawal by Subject	51	174
Death	6	9
Alternative therapy	4	8
Other complicating disease	1	9
Other reasons	7	26
Other	0	2
Did not start therapy	12	17

  Baseline Characteristics

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Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized patients

Reporting Groups

	Description
Arm I (Chemotherapy)	Patients receive one of the following. For all, treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. REGIMEN 1: Vinorelbine ditartrate 30 mg/m2 IV on days 1 and 8, cisplatin 75 mg/m2 IV over 60 minutes on day 1 REGIMEN 2: Docetaxel 75 mg/m2 IV and cisplastin 75 mg/m2 IV on day 1 REGIMEN 3: Gemcitabine hydrochloride 1200 mg/m2 IV on days 1 and 8, cisplatin 75 mg/m2 IV on day 1 REGIMEN 4 (non-squamous histology only): Pemetrexed disodium 500mg/m2 IV and cisplatin 75 mg/m2 IV on day 1 Cisplatin: Given IV Docetaxel: Given IV Gemcitabine Hydrochloride: Given IV Pemetrexed Disodium: Given IV Vinorelbine: Given IV
Arm II (Chemotherapy, Bevacizumab)	Patients receive chemotherapy as in Arm I. Patients also receive bevacizumab IV over 30-90 minutes on day 1. Treatment with bevacizumab repeats every 21 days for up to 1 year. Bevacizumab: Given IV Cisplatin: Given IV Docetaxel: Given IV Gemcitabine Hydrochloride: Given IV Pemetrexed Disodium: Given IV Vinorelbine: Given IV
Total	Total of all reporting groups

Baseline Measures

	Arm I (Chemotherapy)	Arm II (Chemotherapy, Bevacizumab)	Total
Overall Participants Analyzed; [Units: Participants]	749	752	1501
Age; [Units: Years]; Mean (Standard Deviation)	60.7 (9.0)	60.8 (8.7)	60.8 (8.8)
Sex: Female, Male; [Units: Participants]; Count of Participants
Female	374 49.9%	381 50.7%	755 50.3%
Male	375 50.1%	371 49.3%	746 49.7%
Ethnicity (NIH/OMB); [Units: Participants]; Count of Participants
Hispanic or Latino	19 2.5%	29 3.9%	48 3.2%
Not Hispanic or Latino	680 90.8%	688 91.5%	1368 91.1%
Unknown or Not Reported	50 6.7%	35 4.7%	85 5.7%
Race (NIH/OMB); [Units: Participants]; Count of Participants
American Indian or Alaska Native	1 0.1%	5 0.7%	6 0.4%
Asian	22 2.9%	16 2.1%	38 2.5%
Native Hawaiian or Other Pacific Islander	3 0.4%	2 0.3%	5 0.3%
Black or African American	74 9.9%	57 7.6%	131 8.7%
White	642 85.7%	660 87.8%	1302 86.7%
More than one race	0 0.0%	0 0.0%	0 0.0%
Unknown or Not Reported	7 0.9%	12 1.6%	19 1.3%
Chemotherapy; [Units: Participants]; Count of Participants
Cisplatin/Vinorelbine	187 25.0%	190 25.3%	377 25.1%
Cisplatin/Docetaxel	172 23.0%	171 22.7%	343 22.9%
Cisplatin/Gemcitabine	142 19.0%	141 18.8%	283 18.9%
Cisplatin/Pemetrexed	248 33.1%	249 33.1%	497 33.1%
Unknown/Missing	0 0.0%	1 0.1%	1 0.1%
Histology; [Units: Participants]; Count of Participants
Squamous	216 28.8%	206 27.4%	422 28.1%
Adenocarcinoma	424 56.6%	450 59.8%	874 58.2%
Large cell	22 2.9%	16 2.1%	38 2.5%
Bronchioloalveolar carcinoma (BAC)	8 1.1%	5 0.7%	13 0.9%
Not otherwise specified (NOS)	24 3.2%	16 2.1%	40 2.7%
Combined/mixed	45 6.0%	48 6.4%	93 6.2%
Other	10 1.3%	10 1.3%	20 1.3%
Unknown/missing	0 0.0%	1 0.1%	1 0.1%
Performance Status; [Units: Participants]; Count of Participants
Fully active	439 58.6%	440 58.5%	879 58.6%
Ambulatory	310 41.4%	310 41.2%	620 41.3%
Unknown/missing	0 0.0%	2 0.3%	2 0.1%
Urine protein:creatinine (UPC) ratio; [Units: Ratio]; Mean (Standard Deviation)	0.31 (3.10)	0.18 (0.92)	0.25 (2.28)
Urine protein; [Units: mg/dL]; Mean (Standard Deviation)	95.26 (32.28)	100.25 (32.28)	97.79 (41.86)

  Outcome Measures

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1. Primary:

Overall Survival [ Time Frame: From registration to death, up to 10 years ]

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2. Secondary:

Disease-free Survival [ Time Frame: From registration to death, up to 10 years ]

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3. Other Pre-specified:

Perform Analyses of Tissue and Blood to Establish Factors That Predict for Clinical Outcome in Patients Receiving Chemotherapy, With or Without Bevacizumab, for Resected Early Stage NSCLC. [ Time Frame: From registration to death, up to 10 years ]

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4. Other Pre-specified:

To Determine Whether Smoking Status is Linked to Outcome for Patients With Resected Stage IB – IIIA NSCLC Treated With Chemotherapy With or Without Bevacizumab in the Adjuvant Setting. [ Time Frame: From registration to death, up to 10 years ]

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5. Other Pre-specified:

Toxicity Rates as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 [ Time Frame: Up to 1 year post-treatment ]

Results not yet reported.   Anticipated Reporting Date:   No text entered.  

  Serious Adverse Events

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  Other Adverse Events

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  Limitations and Caveats

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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Certain Agreements:  

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is: 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. 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 more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo. Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.

Results Point of Contact:  

Name/Title: Study Statistician
Organization: ECOG-ACRIN Statistical Center
phone: 617-632-3012

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Wakelee HA, Dahlberg SE, Keller SM, Tester WJ, Gandara DR, Graziano SL, Adjei AA, Leighl NB, Aisner SC, Rothman JM, Patel JD, Sborov MD, McDermott SR, Perez-Soler R, Traynor AM, Butts C, Evans T, Shafqat A, Chapman AE, Kasbari SS, Horn L, Ramalingam SS, Schiller JH; ECOG-ACRIN. Adjuvant chemotherapy with or without bevacizumab in patients with resected non-small-cell lung cancer (E1505): an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1610-1623. doi: 10.1016/S1470-2045(17)30691-5. Epub 2017 Nov 9.

Responsible Party:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00324805 History of Changes
Other Study ID Numbers:	NCI-2009-00509; NCI-2009-00509 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); CDR0000475774 ( Registry Identifier: Clinical Data Repository ); E1505 ( Other Identifier: ECOG-ACRIN Cancer Research Group ); E1505 ( Other Identifier: CTEP ); U10CA180820 ( U.S. NIH Grant/Contract ); U10CA021115 ( U.S. NIH Grant/Contract )
First Submitted:	May 10, 2006
First Posted:	May 11, 2006
Results First Submitted:	January 12, 2018
Results First Posted:	February 14, 2018
Last Update Posted:	February 14, 2018