This section was clarified to direct questions regarding eligibility to the study data manager.

Transcription

1 For Protocol Amendment 8 to: RTOG 0839, Randomized Phase II Study of Pre-Operative Chemoradiotherapy +/- Panitumumab (IND #110152) Followed by Consolidation Chemotherapy in Potentially Operable Locally Advanced (Stage IIIA, N2+) Non-Small Cell Lung Cancer NCI/Local Protocol #: RTOG-0839/RTOG 0839 NCI Protocol Version Date: October 9, 2014 Global Title pages Eligibility Checklist Change References to RTOG were replaced with NRG Oncology. References to the RTOG Biospecimen Resource were replaced with NRG Oncology Biospecimen Bank. The Principal Investigator/Medical Oncology s institutional affiliation and contact information was updated. On the 2 nd title page, this amendment was added to the Document History table. The CTSU Address and Contact Information table was deleted from the 3 rd title page. The third sub-question under question 1 of the Eligibility Checklist was amended to clarify that the diameter of involved N2 nodes are 3.0 cm. This section was clarified to direct questions regarding eligibility to the study data manager. This section was amended to clarify that the diameter of involved N2 nodes cannot exceed 3.0 cm. This section was updated to reflect new Imaging and Radiation Oncology Core (IROC) processes/logistics This section was updated to reflect new IROC processes/logistics and These sections were updated to reflect new IROC processes/logistics. 5.5 Pre-registration requirements for surgeon credentialing contacts were updated The first full paragraph was amended to replace the reference to a Cooperative Group to a lead protocol organization. In the final bullet, obsolete instructions for enrolling as an RTOG member site were removed. 6.0 The note was deleted to amend this section to current standard text This section was amended for clarity and These sections were amended for clarity , 6.5.2, These sections were amended for clarity.

2 Global Change References to RTOG were replaced with NRG Oncology. References to the RTOG Biospecimen Resource were replaced with NRG Oncology Biospecimen Bank RTQA please provide brief rationale added for clarification 7.0 The obsolete reference to the RTOG Procedures Manual was removed. 7.3 The reference to the package insert and investigator brochure was removed CTEP s AE reporting requirements were updated The section was amended for clarification to reflect changes made in 6. For Consent Amendment 8 to: RTOG 0839, Randomized Phase II Study of Pre-Operative Chemoradiotherapy +/- Panitumumab (IND #110152) Followed by Consolidation Chemotherapy in Potentially Operable Locally Advanced (Stage IIIA, N2+) Non-Small Cell Lung Cancer NCI/Local Protocol #: RTOG-0839/RTOG 0839 NCI Protocol Version Date: October 9, 2014 Global Change Due to the transition to the National Clinical Trials Network (NCTN), Radiation Therapy Oncology Group, RTOG Headquarters, and RTOG were replaced with NRG Oncology, or deleted, as appropriate, throughout the consent form. Possible Side Effects of Carboplatin The table was replaced with the most recently updated table version dated May 7, Possible Side Effects of Panitumumab Possible Side Effects of Radiation Therapy to the Lungs The table was replaced with the most recently updated table version dated March 13, The title of the table was changed from Possible Side Effects of Radiation Therapy to the Chest to Possible Side Effects of Radiation Therapy to the Lungs. The list of side effects were revised to include the most current information.

3 For Protocol Amendment 7 to: RTOG 0839, Randomized Phase II Study of Pre-Operative Chemoradiotherapy +/- Panitumumab (IND #110152) Followed by Consolidation Chemotherapy in Potentially Operable Locally Advanced (Stage IIIA, N2+) Non-Small Cell Lung Cancer NCI/Local Protocol #: RTOG-0839/RTOG 0839 NCI Protocol Version Date: March 10, 2014 Global Title pages Schema page 5.1.1, 5.1.2, 5.2.2, 5.3.1, 5.3.3, 5.6 Change As required by CTEP, references to Adverse Event Reporting System (AdEERS) have been changed to CTEP Adverse Event Reporting System (CTEP-AERS) throughout the protocol. As required by CTEP, Radiation Therapy Oncology Group was replaced NRG Oncology on all title pages. On the 2 nd title page, this amendment was added to the Document History table. As required by CTEP, Radiation Therapy Oncology Group was replaced NRG Oncology. In these sections, Radiologic Physics Center (RPC) was updated to IROC (Imaging and Radiation Oncology Core) Houston, and when included, the web address for RPC was amended to the web address for IROC Houston In the 2 nd paragraph, the RTOG was updated to IROC. 6.9 Throughout this section, RTOG was updated to IROC Philadelphia-RT This section was amended to include the rare risk of Stevens-Johnson syndrome and toxic epidermal necrolysis, as received from the pharmaceutical supporter, Amgen The last paragraph under Preliminary Dosimetry Information was updated. Appendix VI The 4 th paragraph describing the rare risk of Steven-Johnson syndrome and toxic epidermal necrolysis was added to be consistent with changes made in

4 For Consent Amendment 7 to: RTOG 0839, Randomized Phase II Study of Pre-Operative Chemoradiotherapy +/- Panitumumab (IND #110152) Followed by Consolidation Chemotherapy in Potentially Operable Locally Advanced (Stage IIIA, N2+) Non-Small Cell Lung Cancer NCI/Local Protocol #: RTOG-0839/RTOG 0839 NCI Protocol Version Date: March 10, st page The version date was amended to correspond to the amendment of the protocol. What side effects or risks can I expect from being in the study? Under Possible Side Effects of Panitumumab, the rare risk of Stevens-Johnson syndrome and toxic epidermal necrolysis was added. The risk/benefit profile for this agent is unchanged. At CTEP s request, the Table Version Date and the risks of paclitaxel were amended.

5 For Protocol Administrative Update of RTOG 0839, Randomized Phase II Study of Pre-operative Chemoradiotherapy +/- Panitumumab (IND #110152) Followed by Consolidation Chemotherapy in Potentially Operable Locally Advanced (Stage IIIA, N2+) Non-Small Cell Lung Cancer NCI/Local Protocol #: RTOG-0839/RTOG 0839 NCI Protocol Version Date: 11/26/14 (Update broadcast: 1/7/14) 12.2 Change The name of the form for submission of digital data via TRIAD was updated to DDSI.

6 For Protocol Amendment 6 to: RTOG 0839, Randomized Phase II Study of Pre-Operative Chemoradiotherapy +/- Panitumumab (IND #110152) Followed by Consolidation Chemotherapy in Potentially Operable Locally Advanced (Stage IIIA, N2+) Non-Small Cell Lung Cancer NCI/Local Protocol #: RTOG-0839/RTOG 0839 NCI Protocol Version Date: 11/26/13 Title pages Table of Contents Change On the 2 nd title page, this amendment was added to the Document History table. A 3 rd title page was added in order to update the protocol with the current CTSU contact information table (to be consistent with s 5.6 and 5.7). The table was regenerated to include the addition of The 2 nd sentence was updated to current RTOG standard text , 5.3.2, 6.0, 6.1.3, 6.6, 6.9, 12.1, and 12.2 RTOG is now using TRIAD to collect RT digital data. TRIAD provides sites participating in RTOG clinical trials with a secure method to transmit DICOM RT and other digital data. TRIAD anonymizes and validates the images and information objects as they are transferred via the internet. The first 2 paragraphs were added to update the protocol with access requirements for OPEN and TRIAD. The 3 rd paragraph was deleted. These sections were updated to include logistics for TRIAD for RT digital data submission The 3 rd paragraph was added to update this section to current RTOG RTQA text. 5.4 This section was added to update the protocol with instructions regarding submission of digital RT data using TRIAD (and subsequent sections were appropriately renumbered). 5.6 In the 2 nd paragraph, the phone number for PMB was updated. 6.0 and The timeframe for start of protocol treatment in these sections was expanded from 7 to 14 days to allow more flexibility for sites. In the 2 nd paragraph, the drug supply was corrected from patient specific to study specific. Below the table, the phone number for the FCS Help Desk was updated The 3 rd paragraph was updated with CTEP s required text and These sections were updated to current RTOG Biospecimen Resource text. In the 2 nd row under Submitted as, a parenthetical phrase was added to update the table to current RTOG Biospecimen Resource text. In the 2 nd paragraph, the phrase, Trackable FFPE and All, was added to update the section to current RTOG Biospecimen Resource text.

7 11.2 Appendix V Change In the 1 st paragraph, the link to RECIST was updated. The 2 nd paragraph was formatted as , titled Radiographic Response, and the text was updated to RECIST, v. 1.1 to be consistent with the 1 st paragraph. Subsequent sections were appropriately renumbered. The 2 nd and 3 rd paragraphs were updated to current RTOG Biospecimen Resource text.

8 For Consent Amendment 6 to: RTOG 0839, Randomized Phase II Study of Pre-Operative Chemoradiotherapy +/- Panitumumab (IND #110152) Followed by Consolidation Chemotherapy in Potentially Operable Locally Advanced (Stage IIIA, N2+) Non-Small Cell Lung Cancer NCI/Local Protocol #: RTOG-0839/RTOG 0839 NCI Protocol Version Date: 11/26/13 1 st page The version date was amended to correspond to the amendment of the protocol. What side effects or risks can I expect from being in the study? Will my medical information be kept private? Under Possible Side Effects of Radiation Therapy to the Chest, in each section of the table, the phrase, In 100 people receiving Carboplatin, was corrected to In 100 people receiving radiation therapy. No side effects were changed. CTSU was added to the organizations that may access medical records to be consistent with s 5.6 and 5.7 of the protocol.

9 For Protocol Amendment 5 to: RTOG 0839, Randomized Phase II Study of Pre-Operative Chemoradiotherapy +/- Panitumumab (IND #110152) Followed by Consolidation Chemotherapy in Potentially Operable Locally Advanced (Stage IIIA, N2+) Non-Small Cell Lung Cancer NCI/Local Protocol #: RTOG-0839/RTOG 0839 NCI Protocol Version Date: 7/24/13 1 st Title page Change Dr. Edelman s affiliation and contact information were amended. 2 nd Title page This amendment was added to the Document History table. The version date of the protocol was bolded in the Document History table to update the protocol to current RTOG standards. Eligibility Checklist On pages 3 and 4, questions 1 through 27 were amended to be consistent with OPEN registration. 3.0 The 2 nd sentence was added to update this section to current RTOG standard text An alternative to the formula to determine the predicted post-resection FEV1, segment counting, was added The last sentence of the 2 nd paragraph was updated to current RTOG standard text This section was updated to current RTOG standard text This section was updated to current RTOG standard text and The 2 nd paragraph was amended and the 3 rd paragraph was deleted to update this section to current RTOG standard text. These sections were updated to current RTOG standard text. 5.6 This section was amended for OPEN Registration. 6.0 The 2 nd sentence was added to provide instructions regarding the pre-plan. 7.4 and 7.5 The 1 st sentence was added to update each section to current RTOG standard text , , and Instructions regarding a Paclitaxel Infusion Reaction were added in the table and in footnote d below the table (the subsequent footnote was appropriately re-lettered as e ). Instructions regarding a Paclitaxel Infusion Reaction were added in the table and in footnote c below the table. These sections were updated to current RTOG standard text.

10 Change This section was updated to current CTEP text This section was updated to current RTOG standard text The 4 th bulleted item was amended. 10.2, , , and These sections were updated to current RTOG Biospecimen Resource text In the table, in the 2 nd column for DNA, a note was added. Appendix V Throughout this appendix, the abbreviation for Specimen Transmittal (STF), was corrected to ST. In addition, the abbreviation for Specimen Transmittal Form (STF), was corrected to ST Form.

11 For Consent Amendment 5 to: RTOG 0839, Randomized Phase II Study of Pre-Operative Chemoradiotherapy +/- Panitumumab (IND #110152) Followed by Consolidation Chemotherapy in Potentially Operable Locally Advanced (Stage IIIA, N2+) Non-Small Cell Lung Cancer NCI/Local Protocol #: RTOG-0839/RTOG 0839 NCI Protocol Version Date: 7/24/13 1 st page The version date was amended to correspond to the amendment of the protocol. What side effects or risks can I expect from being in the study? About Using Tissue for Research The side effects of radiation to the chest were reformatted to be consistent with CTEP s current condensed risk profiles. The side effects for paclitaxel and carboplatin were amended to CTEP s current condensed risk profiles. The side effects for panitumumab were amended to incorporate CTEP s risk profile for this agent. The risks are comparable to the package insert. Under Risks, 5 paragraphs were added to update this section to standard RTOG text.

12 For Protocol Amendment #4 to: RTOG 0839, Randomized Phase II Study of Pre-Operative Chemoradiotherapy +/- Panitumumab (IND #110152) Followed by Consolidation Chemotherapy in Potentially Operable Locally Advanced (Stage IIIA, N2+) Non-Small Cell Lung Cancer NCI/Local Protocol #: RTOG 0839 NCI Protocol Version Date: March 21, 2013 (Broadcast date: April 8,, 2013) Change Global To comply with CTEP s new formatting/document requirements, the protocol was reformatted and the sample consent was removed from the appendices. The appendices were appropriately renumbered throughout the protocol. The informed consent continues to be available via MS Word on the protocol documents section of the main protocol page. 1.1 A header was added to this section 2nd Title Page The document history table was updated with the date for Amendment nd paragraph, the last sentence was revised for clarity. Systematic mediastinal lymph node evaluation replaced mediastinal nodal dissection This paragraph was amended to clarify the credentialing process This section was amended to provide clarity The table for Arms 1 and 2 was amended for clarity. Day 21 has been changed to Day This section was updated to align with RTOG standard text for investigational agents The reference to NCI Guidelines was updated The Note in the table was deleted to be consistent with AdEERS reporting requirements.

13 Change 8.2 The surgical techniques have been updated throughout this section to align with current practice. 8.3 The phrase typically, Lasix 20 mg bid is used daily was removed Muscle flaps was replaced with soft tissue coverage for clarification An unacceptable deviation was added to the list The process for submitting final dosimetry information was updated The ITC contact information was updated. References The reference Gray, RJ. was amended. Appendix I The table was updated to allow within 6 weeks for tumor location, type and size. Appendix VII The Thoracic Surgeon Questionnaire was amended to align with the surgical requirements for this study.

14 For Protocol Consent Amendment #4 to: RTOG 0839, Randomized Phase II Study of Pre- Operative Chemoradiotherapy +/- Panitumumab (IND #110152) Followed by Consolidation Chemotherapy in Potentially Operable Locally Advanced (Stage IIIA, N2+) Non-Small Cell Lung Cancer NCI/Local Protocol #: RTOG 0839 NCI Protocol Version Date: March 21, 2013 (Broadcast date: April 8, 2013) Version date A version date was added to the informed consent form per current RTOG standard. What are the costs of taking part in this study? The link is broken and has been removed.

15 SUMMARY OF CHANGES Amendment 3, Version Date: August 16, 2012 RTOG 0839, Randomized Phase II Study of Pre-operative Chemoradiotherapy +/- Panitumumab Followed by Consolidation Chemotherapy in Potentially Operable Locally Advanced (Stage IIIA, N2+) Non-Small Cell Lung Cancer Study Chair: Martin J. Edelman, , RTOG 0839 has been amended as follows: During the review of a recent serious adverse event, it was found that the case had 2 mediastinal nodes that exceeded the 3 cm limit; this limit already existed in the protocol. The case s lung V20 also exceeded the limits set forth in the protocol. It was felt that these issues led to the development of the grade 5 adverse event. The protocol was amended to emphasize the already existing text regarding the mediastinal nodal size limit as well as the lung V20 constraints, as follows: Schema page: A symbol ( ) was added in both treatment arms next to Concurrent RT, referencing a footnote instructing investigators to see s 6.0 and 6.6 regarding the V20. Eligibility Checklist: Page 1: A subquestion was added under Question 1 concerning the largest diameter of any involved node to be consistent with Page 4: Question 29 was added : The phrase, the maximum nodal diameter not to exceed 3.0 cm, was clarified to the maximum nodal diameter cannot exceed 3.0 cm. 6.0: A note was added regarding required RT pre-planning : The former last paragraph was amended and bolded for emphasis, and an additional bolded paragraph was added below to provide further instructions to investigators regarding the V20. Other Changes 1 st title page: Study Chairs was amended to the current RTOG standard text, Study Team. In addition, the Senior Statistician was amended from Dr. Dignam to Dr. Hu. 2 nd title page: The Version Date was deleted to amend the protocol to the current RTOG standard of bolding the version date of the protocol in the Document History table. In addition, this amendment was added to the Document History table. Eligibility Checklist, p. 3: Under the heading, the 2 nd sentence was added to be consistent with instructions in was deleted, as it was redundant with , and subsequent sections were appropriately renumbered : In the 1 st paragraph, the phrase, stereotactic body radiation therapy (SBRT), was deleted because this study does not involve that treatment technique : In the 1 st sentence, REB was deleted, as the study is open to U.S. sites only. The link to the CTSU-IRB Certification Form was updated concerning translation of documents was deleted, as the study is open to U.S. sites only, and this text does not apply; U.S. sites generally follow a short form method for consenting non-english speaking patients (unless they serve a large population of these patients) : Electa was corrected to Elekta.

16 Other Changes (continued) 6.6.2: CTV1 was corrected to CTV. RTOG 0839, Amendment 3, page : PTV was added to the list of DVH required : In the 2 nd paragraph, the sentence beginning, Any pregnancy, was amended to current RTOG standard text : The phrase, and brain MRI with contrast, was moved to a separate section, (and subsequent sections were appropriately renumbered), to clarify that it is an assessment separate from those in In addition, FDG-PET was corrected to FDG-PET/CT. Appendix I: The heading, When you are finished the additional chemotherapy, was corrected to When you are finished with the additional chemotherapy. In addition, under this heading, the bone scan was deleted, as this assessment is not required in follow up. Appendix II: Under Follow Up, the X for the bone scan was deleted, as this assessment is not required in follow up.

17 SUMMARY OF CHANGES Amendment 2, Version: February 9, 2012 RTOG 0839, Randomized Phase II Study of Pre-operative Chemoradiotherapy +/- Panitumumab Followed by Consolidation Chemotherapy in Potentially Operable Locally Advanced (Stage IIIA, N2+) Non-Small Cell Lung Cancer Study Chair: Martin J. Edelman, , RTOG 0839 has been amended as follows: The following changes were made to the title pages: Dr. Donington s fax number was updated. Dr. Loo was added as the Imaging Co-Chair. Dr. Dignam replaced Dr. Bae as the Senior Statistician. The Activation Date and Update Date were deleted, as this information is provided in the Document History table (the updated Version Date was retained for clarity). The Document History table was updated for this amendment. 1.5: In the 3 rd paragraph, the description of the FLEX trial was corrected to cisplatin, vinorelbine, and cetuximab versus cisplatin and vinorelbine : The 4 th and 5 th sentences were added to provide instructions to sites regarding PET/CT images, reports, and assessment forms : In the note, the phrase, FDG-PET scan, was corrected to FDG-PET/CT scan. 5.4: In the 2 nd paragraph, Dr. Donington s address was corrected. This correction also was made on the 3 rd page of Appendix VIII, Thoracic Surgeon's Questionnaire was amended to current RTOG standard text was added to amend the protocol to current RTOG standard text : The phrase, 6-18 MV beams was corrected to 6-10 MV beams. 7.10: The 5 th paragraph was added to amend the protocol to current RTOG standard text. 7.11: The title of the table and the table were amended to current CTEP requirements : In the 6 th bulleted item, a sentence regarding PET/CT images, reports and assessments forms was added to the 3 rd subsection : The phrase, and medical oncologist was deleted, as this individual does not have to review and sign all post-surgical forms. 10.7: The street address for the RTOG Biospecimen Resource was updated. This change also was made in Appendix VI. 10.8: The link to the Reimbursement and Case Credit Schedule was corrected. 10.9: This section was previously numbered as 10.8, and this was corrected. s and : The last sentence regarding PET/CT images, reports and assessments forms was added to each section.

18 RTOG 0839, Amendment 2, Page 2 The following changes were made to 12.1: The phrase, Pre-Study PET/CT Scan was clarified to Pre-Treatment PET/CT Scan. A note was added to the required timeframe for the Pre-Treatment PET/CT Scan to provide instructions to sites. The Treatment Summary Form was re-named Radiotherapy Form (T1). A sentence was added below the Post-RT PET/CT scan and Report to instruct sites that scans must be on a CD and in DICOM format. In addition, a reference to was deleted. A reference to and a note were added to the required timeframe for the Post-RT PET/CT Scan and Report. 12.2: The form designations, (C1, C3), next to CT data, critical normal structures, all GTV, CTV, and PTV contours were deleted, as these designations are no longer RTOG standard : The 2 nd, 3 rd, and 5 th paragraphs were amended to provide further details regarding assessment of PET/CT scan data to predict outcome. References: A citation for Wahl 2009, referenced in the amended 5 th paragraph of , was added. The following changes were made in Appendix I: Under When you are finished the additional chemotherapy, an evaluation of your overall physical condition, was added to the 1 st and 2 nd bulleted items to be consistent with changes made in Appendix II. Under Will my medical information be kept private?, the 3 rd and 4 th paragraphs were added to amend the sample consent to the current NCI template. Under About Using Tissue, Blood, and Urine for Research, in the 2 nd paragraph, the title for and the link to the information sheet were updated. Under Where can I get more information?, the TTY number was deleted at NCI s request. Appendix II: For the Zubrod Performance Status, the assessment During Consolidation Treatment was corrected from Weekly to q 3 wks, and the assessment was added in both Follow Up columns. Appendix VIII: On the 3 rd page, Dr. Donington s fax number was updated.

19 SUMMARY OF CHANGES Update: July 6, 2011 (Broadcast 7/6/11) RTOG 0839, Randomized Phase II Study of Pre-operative Chemoradiotherapy +/- Panitumumab Followed by Consolidation Chemotherapy in Potentially Operable Locally Advanced (Stage IIIA, N2+) Non-Small Cell Lung Cancer Study Chair: Martin J. Edelman, , RTOG 0839 has been updated as follows: Eligibility Checklist, page 2: Question 11 was updated to be consistent with changes made to in amendment 1.

20 SUMMARY OF CHANGES Amendment 1, June 24, 2011 (Broadcast: 7/6/11) RTOG 0839, Randomized Phase II Study of Pre-operative Chemoradiotherapy +/- Panitumumab Followed by Consolidation Chemotherapy in Potentially Operable Locally Advanced (Stage IIIA, N2+) Non-Small Cell Lung Cancer Study Chair: Martin J. Edelman, , RTOG 0839 has been amended as follows: Eligibility Checklist, page 4: Question 28 was amended to be more specific and to be consistent with the following subquestion : The timeframe for the pathological confirmation of N2 status was expanded to 12 weeks prior to registration to allow institutions more flexibility in meeting this requirement. This change also was made in question 1 (3 rd subquestion) on page 1 of the Eligibility Checklist, 8.1.1, and in Appendix II was reformatted into 2 sections for clarity: for the required MRI with contrast (or CT scan with contrast, if medically indicated), and for the required CT scan with contrast of the lungs and upper abdomen : A timeframe of 6 weeks of registration was added for the whole body FDG-PET scan. This information also was added to : In the last sentence, the phrase, and/or, was corrected to and. 5.4 was amended to request institutions to (vs. fax) the Thoracic Surgeon s Questionnaire to Dr. Donington. This change also was made in Appendix VIII : The link to the Certification Form was updated : In the heading, the word, only was added after U.S. Institutions to clarify that panitumumab is available only to these sites. In addition, the description of the placement of the SASF on the RTOG web site was amended. These changes also were made in : The link to the Password Authorization Form and the address for RTOG web support were updated. 7.10: In the 2 nd paragraph, the link to the RTOG web site was updated : The last 3 sentences were added to provide institutions and investigators with documentation requirements for patients who do not undergo resection and with a definition of a protocol violation , Surgical Quality Assurance Reviews, was amended for clarity was amended to read that Dr. Donington will perform a quality assurance review on each case after complete data has been received at RTOG Headquarters for that case : Under Deviations Unacceptable, the last bulleted item was amended to include documentation of decline in medical condition to be consistent with changes in s 10.3 and 10.4 were amended to current RTOG Biospecimen standards. Continued on next page

21 RTOG 0839, Amendment 1, Page was added to update the protocol to current RTOG Biospecimen standards, and subsequent sections were appropriately renumbered was amended to current RTOG standard text. 10.8: The link to RTOG Patient Tissue Consent Frequently Asked Questions was updated : In the 1 st sentence, the reference to was corrected to : Next to Hard copy isodose distributions for total dose plan, the phrase as described in QA guidelines, was deleted, as was the corresponding note. This is a correction, as these guidelines are not available. The following changes were made in Appendix I: Under What will happen if I take part in this research study? and If you are in group 2, the timeframe for panitumumab was corrected from 7 to 6 weeks. Under When you are finished the additional chemotherapy, an MRI of the brain (or CT scan if indicated was added to be consistent with Appendix II. The risks associated with paclitaxel and carboplatin were amended to be more consistent with the sample consents of other active RTOG clinical trials involving these agents. Under the Less Likely, but Serious risks associated with panitumumab, in the last bulleted item, lunch damage was corrected to lung damage. Under About Using Tissue, Blood, and Urine for Research, in the 1 st paragraph, the phrase, or have had, was added prior to a biopsy. In the 2 nd paragraph, the title and link to NCI s information sheet were updated. The following changes were made in Appendix II: Under the follow-up timeframe for the MRI or CT with contrast of the brain, the X was replaced with If clinically indicated. An MRI or CT of the brain is not required at followup visits unless clinically indicated. Under Assessments, the Chest X-ray was amended to +/- optional chest x-ray to be consistent with Appendix VI was updated to current RTOG Biospecimen Resource standards. Appendices VII and VIII were deleted, as this information is included in the updated Appendix VI, and subsequent appendices were renumbered appropriately on the Index page and throughout the protocol.

22 SUMMARY OF CHANGES Update: February 11, 2011 (Broadcast 2/11/11) RTOG 0839, Randomized Phase II Study of Pre-operative Chemoradiotherapy +/- Panitumumab Followed by Consolidation Chemotherapy in Potentially Operable Locally Advanced (Stage IIIA, N2+) Non-Small Cell Lung Cancer Study Chair: Martin J. Edelman, , RTOG 0839 has been updated as follows: Title page: Dr. Dicker s address was updated. In addition, a Document History table was added to update the protocol to current RTOG standards. 5.4 was updated to indicate a change in process. Dr. Donington will the reviewed site Thoracic Surgeon s Questionnaire to RTOG HQ as well as CTSU. The last page of Appendix X was updated to be consistent with this change. Appendix X: A sentence and parenthetical reference to 5.4 were added to the first paragraph to clarify that surgeon credentialing is a pre-registration requirement.

23 SUMMARY OF CHANGES Update: December 23, 2010 RTOG 0839, Randomized Phase II Study of Pre-operative Chemoradiotherapy +/- Panitumumab Followed by Consolidation Chemotherapy in Potentially Operable Locally Advanced (Stage IIIA, N2+) Non-Small Cell Lung Cancer Study Chair: Martin J. Edelman, , RTOG 0839 has been updated as follows: 5.4 was updated to indicate a change in process. Dr. Donington will her approval of a site s Thoracic Surgeon s Questionnaire to CTSU. Appendix X was updated to be consistent with this change : Information about the shipment of the study agent was updated : This section was amended as required by CTEP to instruct sites to report AML or MDS via AdEERS.