3.1.4 The phrase, and only focal nuclear, was clarified to and/or only focal nuclear.

Transcription

1 For Protocol Amendment 3: RTOG 1221, Randomized Phase II Trial of Transoral Endoscopic Head And Neck Surgery followed by Risk-Based IMRT and Weekly Cisplatin versus IMRT and Weekly Cisplatin for HPV Negative Oropharynx Cancer NCI/Local Protocol #: RTOG-1221/RTOG 1221 NCI Protocol Version Date: August 19, 2014 Section Change Global Radiation Therapy Oncology Group, RTOG Headquarters, and RTOG were replaced with NRG Oncology, or deleted as appropriate, throughout the protocol. 1 st Title The sentence beneath the title was amended to current standard text. page Dr. Zhang s title, affiliation, and address were amended. 2 nd title page This amendment was added to the Document History table. 3 rd title page The table was amended to CTSU s current standard text. Table of The table was regenerated to be consistent with changes made in the protocol. Contents Eligibility Question 4 was amended to be consistent with changes made in Section Checklist, page In the 1 st paragraph, RTOG Headquarters RTQA was replaced with RTQA at NRG Oncology. 3.1 This section was amended to current NRG Oncology standard text The phrase, and only focal nuclear, was clarified to and/or only focal nuclear. 5.0 The 3 rd paragraph was deleted to amend this section to current NRG Oncology standard text. 5.1 Section was amended to current standard text. Section and a table were added to amend the section to current standard text. The former sections and 5.2 were deleted, and subsequent sections were appropriately renumbered. 5.3 This section was amended to current NRG Oncology standard text The 2 nd,4 th, and last paragraphs were amended to current NRG Oncology standard text In the heading, the reference to Section was amended to Section to be consistent with changes made in Section 5.1. The 4 th paragraph was amended for clarity and simplicity The 1 st paragraph was amended for clarity and the table was updated to current standards. 6.7 In the 3 rd row of the 1 st column of the table, the word, or, was added after PTV60, and the asterisk (*) at the end of 60 in PTV60_Eval was deleted, as it was an error. 6.8 This section was amended to current NRG Oncology standard text. 7.0 The 1 st paragraph was deleted to amend this section to current NRG Oncology standard text. 7.5 This section was amended to current NRG Oncology standard text.

2 Section Change 8.3 The text in the former Section 8.5 was moved to this section, the title of the section was amended, the 2 nd sentence was added regarding the timeframe for the neck dissection, and the former Section was deleted as it was redundant with text later in Section 8.3. Subsequent sections were appropriately renumbered This section was amended to current NRG Oncology standard text In the 8 th paragraph, RTOG coordinating center was replaced with NRG Oncology The 2 nd paragraph was amended to current NRG Oncology standard text The 1 st sentence and 1 st row of the table were amended to current NRG Oncology standard text The title and 1 st sentence were amended to current NRG Oncology standard text. Appendix I, Assessment during Treatment The table was reformatted to include a new time point, Weekly during RT or chemort, and assessments were added for this time point. For Consent Amendment 3: RTOG 1221, Randomized Phase II Trial of Transoral Endoscopic Head And Neck Surgery followed by Risk-Based IMRT and Weekly Cisplatin versus IMRT and Weekly Cisplatin for HPV Negative Oropharynx Cancer NCI/Local Protocol #: RTOG-1221/RTOG 1221 NCI Protocol Version Date: August 19, 2014 Section Header What will happen if I take part in this research study? What side effects or risks can I expect from being in the study? Will my medical information be kept private? Change The version date of the sample consent and of the protocol version to which it is attached was changed for this amendment. Under During the study, the heading, Weekly during radiation therapy was amended to Weekly during radiation or chemoradiation, and 2 bulleted items were added to be consistent with changes made in Appendix I of the protocol. The risks and side effects related to radiation to the head and neck were amended to NRG Oncology standard text for this disease site. The Radiation Therapy Oncology Group (RTOG) was replaced with NRG Oncology.

3 For Protocol Amendment 2: RTOG 1221, Randomized Phase II Trial of Transoral Endoscopic Head And Neck Surgery followed by Risk-Based IMRT and Weekly Cisplatin versus IMRT and Weekly Cisplatin for HPV Negative Oropharynx Cancer NCI/Local Protocol #: RTOG-1221/RTOG 1221 NCI Protocol Version Date: February 19, 2014 Section Change Global As required by CTEP, references to the Adverse Event Reporting System (AdEERS) have been changed to CTEP Adverse Event Reporting System (CTEP-AERS) throughout the protocol. 1 st Title page As required by CTEP, Radiation Therapy Oncology Group was replaced with NRG Oncology. As required by CTEP, a sentence was added beneath the title specifying NRG Oncology as leading the trial with participation of the network of NCTN researchers: the Alliance, ECOG-ACRIN, and SWOG. Dr. Holsinger s contact information was updated. 2 nd title page NRG Oncology and the protocol number and title were added to update this page to current standards. This amendment was added to the Document History table. 3 rd title page This page was added to accommodate the CTSU address and contact information table. Schema page As required by CTEP, Radiation Therapy Oncology Group was replaced with NRG Oncology. The description of Arm 1 was amended to clarify that post-adjuvant therapy +/- IMRT and +/- cisplatin is given only to high-risk patients. 1.4 In the 8 th paragraph, the phrase, With margins > 2 mm, was amended to With margins > 3 mm. This change was made to harmonize the description of margins and margin status with the current RTOG trial, 1216, and ECOG s counterpart to RTOG 1221, ECOG This section was amended to current standard text A note was added as the 3 rd paragraph to provide information to sites concerning credentialing. 6.0 A note was added as the 3 rd paragraph to clarify that adjuvant radiation therapy is given only to high-risk patients. 6.1 Paragraphs 1 through 3 were amended for clarity In the 4 th paragraph, retroslyloid regiona was corrected to retrostyloid region. In the 5th paragraph, the 2 nd and 3 rd sentences were amended for clarity. In the 2 nd bulleted item below the 5 th paragraph, PRV was corrected to PTV In the last paragraph, the 3 rd sentence was amended for clarity The required RT structures table was updated Items 3, 4, and 5 were amended for clarity. 6.7 The compliance tables for both arms were amended for clarity. 7.1 The phrase, 5 or more, was amended to 5 to be consistent with Section In the 2 nd paragraph, the description of grade 3 neutropenic fever was corrected to be consistent with CTCAE, v The 5 th sentence was amended for clarity , 8.2.2, 8.3.3, 8.3.5, 8.3.6, The surgical margins in these sections were amended from 2 mm to 3 mm to harmonize the description of margins and margin status with the current RTOG trial, 1216, and ECOG s counterpart to RTOG 1221, ECOG The 3 rd sentence was added for clarity.

4 Section Change The 3 rd bulleted item, Close margin was deleted as it was redundant with the 1 st bullet In the 1 st sentence, the phrase, to RTOG Headquarters, was deleted to update this section to current RTQA standard text. The section referenced was corrected to The paragraph below Table 1 was amended for clarity and to provide details of the allowable MBS capture rates. In Table 2, a reference to further details was added in the definition of frame rate The row beginning Upon submission of the digital data via TRIAD was amended to current RTQA standard text The heading and the text of this section was amended to current RTQA standard text The 2 nd sentence was added to instruct sites to de-identify MBS files prior to uploading to TRIAD In the 4 th paragraph, 2 mm was replaced with 3 mm to be consistent with changes made in Sections 1.4, 8.2, and 8.3. Appendix IX Question 2 was amended to be consistent with changes made in Section

5 For Consent Amendment 2: RTOG 1221, Randomized Phase II Trial of Transoral Endoscopic Head And Neck Surgery followed by Risk-Based IMRT and Weekly Cisplatin versus IMRT and Weekly Cisplatin for HPV Negative Oropharynx Cancer NCI/Local Protocol #: RTOG-1221/RTOG 1221 NCI Protocol Version Date: February 19, 2014 Section Header What will happen if I take part in this research study? Study Plan What side effects or risks can I expect from being in the study? About Using Tissue for Research Change The version date of the sample consent and of the protocol version to which it is attached was changed for this amendment. In the 3 rd paragraph, the 2 nd sentence was amended to be consistent with the 3 rd paragraph under Why is this study being done? In the list of bulleted items under Before you begin the study (for all patients), the item concerning a CT scan with contrast, was amended from to increase the differences to better show the differences. The schedule under You will need these tests and procedures in follow-up visits was amended to be consistent with the schedule of follow up under How long will I be in the study and with Appendix I of the protocol. The description of adjuvant treatment for Group 1 was amended to clarify that adjuvant treatment is given only to high-risk patients ( if there is concern that not all of the cancer has been removed ) to be consistent with clarifications made in the protocol. Under the Rare and Serious risks of minimally invasive surgery and neck dissection, the risk of Bleeding from the mouth was amended for clarity. Under Things to Think About, in the 3 rd paragraph, the template text, xyz, was replaced with your doctor or institution. The text under Risks was updated to current standard text.

6 For Protocol Administrative Update: RTOG 1221, Randomized Phase II Trial of Transoral Endoscopic Head And Neck Surgery followed by Risk-Based IMRT and Weekly Cisplatin versus IMRT and Weekly Cisplatin for HPV Negative Oropharynx Cancer NCI/Local Protocol #: RTOG 1221 NCI Protocol Version Date: October 2, 2013 (Broadcast October 30, 2013) Section Change The CTSU address for faxing the Modified Barium Swallow (MBS) Credentialing Checklist was updated in the following sections of the protocol: Section 5.6 Appendix IX, MBS Credentialing Checklist In the Standard Names table for digital RT data submission, an extra space in front of the R and L of the right and left parotid glands was removed. Data for these structures should be submitted under standard names Parotid_R and Parotid_L. i RTOG 1221, Version Date October 2, 2013

7 For Protocol Amendment #1: RTOG 1221, Randomized Phase II Trial of Transoral Endoscopic Head And Neck Surgery followed by Risk-Based IMRT and Weekly Cisplatin versus IMRT and Weekly Cisplatin for HPV Negative Oropharynx Cancer NCI/Local Protocol #: RTOG 1221 NCI Protocol Version Date: October 2, 2013 (Broadcast October 10, 2013) Section Change Patients with T3 HPV-negative oropharyngeal carcinoma will not be eligible for participation in this study. Accordingly, the following sections of the protocol were revised: Title Page ehns (TLM, TORS)/Device/IDE were deleted from the protocol agent table; the document history table was updated for the pre-activation revision. Schema The stratification variables were updated to remove references to T3 tumors (T stage and Page N stage). The brief description of the patient population for the study was revised. Eligibility Page 1, question 3; page 3, questions Checklist 1.4 Third paragraph Paragraph under Post-operative Indication for Treatment of the Contralateral Neck Paragraph, under No Indication for Post-operative Radiation Therapy Paragraph beginning For the control arm First paragraph under Rationales for Exclusion of T3-4 and N2c Tumors 2.2 In secondary objective 2.2.2, T3 tumors was replaced with HPV-negative tumors T3, N0-2b, with only well-lateralized exophytic T3 tumors not approaching within 1 cm of midline, and amenable to transoral ehns was revised to with tumors not approaching within 1 cm of midline, and amenable to transoral ehns Under Neck node coverage for both arms, T1-T3, N0-N2b was revised to T1-T2, N1- N2b. 7.5 The section title was revised. 8.0 Investigational device component was deleted from the section title. 8.2 In the paragraph beginning Any transoral approach :, T1-T3N0-N2b was revised to T1-T2;N1-N2b In the second sentence, 3 mm microscopic margins was revised to 2-3 mm microscopic margins. The fifth sentence, beginning, However, the constrictor margin, was deleted at least 3 mm grossly was revised to at least 2 mm grossly mm was revised to 2 mm The last sentence, For cn0, cervical nodal level IIb may be spared, was replaced with Level IIb may be spared based on the surgeon s judgment, for N1 patients. But for patients with N2b neck classification, strong consideration should be given to dissecting level II-b The first sentence was revised for clarity. 8.8 The section title and the paragraph at the end of the section were revised for all patients and patients with selected T3 tumors was deleted from the end of the secondary endpoint in this subsection.

8 Section Change 13.3 The estimates for annual accrual and the approximate accrual period were revised The expected accrual/accrual period numbers were updated The expected accrual numbers were updated Second sentence: The experimental arm will be compared to the control arm when the 144 patients have been followed for 2.3 years. was revised to The experimental arm will be compared to the control arm when the 144 patients have been followed for 2 years The last sentence of the second paragraph was deleted The paragraph beginning, Six months or one year PFS rate will be assessed for the control arm, was inserted at the end of the section First paragraph, the T stage and N stage stratification details were revised. Other changes to the protocol include: 5.5 The pre-registration requirements for surgeon credentialing were updated: A new Section was inserted; the subsequent sections were renumbered The sentence regarding pregnancy at the end of the section was revised Per CTEP, the second paragraph was inserted to provide information regarding reimbursement distribution within the NCI National Clinical Trials Network (NCTN) Program DFS was corrected to PFS in the second sentence The beginning of the first sentence was revised. Appendix V Head & Neck Surgeon's Questionnaire Dr. Holsinger s phone number was updated; instructions for the site research associate were added at the end of the appendix.

9 Sample consent form version: October 2, 2013 To be attached to protocol version: October 2, 2013 For Protocol Consent Amendment #1: RTOG 1221, Randomized Phase II Trial of Transoral Endoscopic Head And Neck Surgery followed by Risk-Based IMRT and Weekly Cisplatin versus IMRT and Weekly Cisplatin for HPV Negative Oropharynx Cancer NCI/Local Protocol #: RTOG 1221 NCI Protocol Version Date: October 2, 2013 (Broadcast October 10, 2013) Section Change Patients with T3 HPV-negative oropharyngeal carcinoma will not be eligible for participation in this study. The following sections of the consent were revised accordingly: What will happen if I take part in this research study? What side effects or risks can I expect from being in the study? 2 nd paragraph under If you are in Group 1 (often called "Arm 1") : The last sentence in this paragraph, referencing T3 tumors, was deleted. The paragraph above reproductive risks was deleted. i RTOG 1221

10 For Protocol Administrative Update: RTOG 1221, Randomized Phase II Trial of Transoral Endoscopic Head And Neck Surgery followed by Risk-Based IMRT and Weekly Cisplatin versus IMRT and Weekly Cisplatin for HPV Negative Oropharynx Cancer NCI/Local Protocol #: RTOG 1221 NCI Protocol Version Date: July 30, 2013 (Update broadcast: September 5, 2013) Section Title Page Change In the Protocol Agent table, n/a and Pre-IDE number were inserted in the ehns (TLM, TORS) row. The Document History table was updated with the Pre-activation and Update details. 5.0 The first paragraph was added to provide instructions to sites for access to OPEN, Rave, and TRIAD and to provide information about TRIAD use and installation. 5.3 A new section was inserted to provide details for submission of dosimetry digital data to RTOG using TRIAD; the subsequent sections were renumbered In the fourth paragraph, the first bulleted item was updated to be consistent with changes made in Section 5.0. In the last bulleted item, member, was inserted to update this section to current OPEN text. 6.0 The first paragraph was added to provide instructions to sites for TRIAD use and installation The first paragraph was updated to be consistent with changes made in Section 5.0. Note was deleted from the beginning of the second paragraph The text above the table was revised to refer sites to Section 5.0 for TRIAD account access and installation instructions This section was deleted. Sites are referred to Section 5.0 for TRIAD submission in Section Appendix V Head & Neck Surgeon's Questionnaire: The protocol section number referenced for the surgeon credentialing pre-registration requirements was updated. Appendix IX Modified Barium Swallow (MBS) Credentialing Checklist: The protocol section number referenced for the MBS credentialing pre-registration requirements was updated.