- Email: [email protected]
Report on NRG Oncology and the GOG Foundation
Gynecologic Oncology 139 (2015) 3–4
Contents lists available at ScienceDirect
Gynecologic Oncology journal homepage: www.elsevier.com/locate/ygyno
Conference Report Report on NRG Oncology and the GOG Foundation
This report will provide an update on NRG Oncology and the GOG Foundation and will review the scientific and educational activities during the NRG Oncology Summer Semi-Annual Meeting in Denver, CO, held on July 16–19, 2015. 1. NRG Oncology. Transitioning from the Gynecologic Oncology Group (GOG), a gynecologic cancer specific cooperative group that existed for nearly 50 years, to the NCTN's NRG Oncology, developed as a result of the NCI's restructuring of their clinical trial program, was not easy. It took a lot of hard work by many dedicated individuals to blend the operational and cultural aspects of three legacy groups (GOG, RTOG, NSABP) and to submit a competitive grant application. As a result of that effort, NRG Oncology has exceeded expectations during its first year of operation. NRG Oncology has accrued more patients to clinical trials and had more new trials approved by the NCI than any of the other three NCTN Operational Centers. The leadership is deeply appreciative of the perseverance and dedication of the countless number of investigators, research staff and employees that made this transition as smooth and successful as possible. Much work remains to ensure the continued success of NRG Oncology but it is off to a great start. 2. GOG Foundation The GOG Foundation is also thriving. The Foundation's Partners Program has completed three pharmaceutical supported trials. Several other trials have recently been activated and more are in development. As the NCI focuses more on smaller biomarker driven trials, these GOG Foundation trials will offer added opportunities for your patients to gain access to cutting edge therapies. Contact the GOG Foundation if you have an interest in participating in these trials. In addition, the GOG Foundation is quite supportive of developing the next generation of gynecologic cancer investigators. The best opportunities to access therapeutic agents in development are to interface with industry's drug development teams. Advisory Boards are often the venue through which the GOG Foundation explores opportunities to bring new therapies from our industry partners into the GOG Foundation's clinical trial portfolio. Young investigators interested in becoming more involved in developing these studies should make it known to the GOG Foundation leadership.
and challenges with development of trials that utilize two or more targeted therapies. Dr. Gwynn Ison from the FDA discussed the regulatory considerations for combinational targeted therapeutics in gynecologic cancer. Other sessions covered examples of active or planned trials investigating the combination of PARP and anti-angiogenic inhibitors, MAPK and PI3K inhibitors, and PD-1 inhibitors and other immunomodulators. These presentations were timely given the number of current combination targeted therapeutic trials for gynecologic cancers recently activated or in development. 4. Ovarian Cancer Trials Speaking of trials, there is now after a longer than desired hiatus an active phase III treatment trial for patients with stage III or IV ovarian cancer. The Partners Program's GOG-3005 trial will evaluate the PARP inhibitor Veliparib in combination with chemotherapy in newly diagnosed patients with high grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer. Eligible patients can be treated after primary debulking or with neoadjuvant chemotherapy. Investigators can choose between dose dense or standard every 3 week paclitaxel to be given in combination with every 3 week carboplatin. Patients will be randomized to either receive chemotherapy alone, chemotherapy with Veliparib, or chemotherapy with Veliparib both during treatment and as a maintenance therapy. The trial will be placebo controlled. Information regarding BRCA mutation status will be assessed on all patients. Other active NCI funded ovarian cancer trials include 1) NRG-CC002, which is conducting perioperative risk assessments in elderly ovarian cancer patients undergoing debulking; 2) GOG-0225, which is evaluating how diet and physical activity can modulate progression free survival in ovarian cancer patients who have completed primary therapy; 3) GOG-0213, which was just amended to accept more patients to evaluate the efficacy of secondary cytoreduction in patients with recurrent ovarian cancer; and 4) NRG-GY003, which is evaluating nivolumab with or without ipilimumab in patients with platinum resistant ovarian cancer. Other important trials are in development and will likely be activated within the year. NRG-GY007, the first of hopefully several trials utilizing the neoadjuvant chemotherapy platform, will investigate ruxolitinib with neoadjuvant chemotherapy in newly diagnosed advanced stage ovarian cancer patients. NRG-GY004 and NRG-GY005 are two trials which will evaluate the PARP inhibitor olaparib and the anti-angiogenic agent cediranib in platinum sensitive and resistant ovarian cancer patients, respectively.
3. Highlights from GOG Foundation's summer semi-annual meeting symposium
5. NCI experimental therapeutic clinical trials network
The Summer Symposium, organized by Dr. John Farley was entitled, “Rational Combination Targeted Therapies for Gynecologic Cancers.” Dr. S. Percy Ivy from the NCI provided an overview of the opportunities
The NCI has changed how it is facilitating development of new investigational drugs. Instead of a mass solicitation for protocol concepts, the NCI will now form a Project Team to draft a preliminary drug,
http://dx.doi.org/10.1016/j.ygyno.2015.08.021
4
Conference Report
biomarker, and assay development plan. The NCI will send out a Request for a Project Team Application and interested investigators with expertise in the investigation drug can apply as either basic, translational, or clinical team members. The participation of young mentored investigation is highly encouraged. The Project Team then proceeds to develop a plan for the investigational agent over a very tight timeline. It is important for those interested in drug development to participate in this new process to help ensure development of clinical trials evaluating exciting new drugs for gynecologic cancers. For more information, contact http://next.cancer.gov. 6. The MATCH Trial NRG Oncology will be participating in the soon to be activated Molecular Analysis for Therapy Choice (MATCH) trial, a part of the President's Precision Medicine Initiative. This phase II trial will enroll 3000 patients with recurrent cancer and use DNA gene sequencing of a tumor biopsy to enroll patients in one of 10 initial treatment arms evaluating drugs that target specific driver mutations. For more information on the MATCH trial, see http://www.cancer.gov/about-cancer/ treatment/clinical-trials/nci-supported/nci-match. 7. ASCO abstract presentations The following select NRG Oncology/GOG Foundation abstracts were presented at the 2015 ASCO Annual Meeting. 7.1. Ovarian cancer Birrer et al. Retrospective analysis of candidate predictive tumor biomarkers (BMs) for efficacy in the GOG-0218 trial evaluating front-line carboplatin-paclitaxel (CP) ± bevacizumab (BEV) for epithelial ovarian cancer (EOC). Lee T et al. CT perfusion as an early biomarker of treatment efficacy in advanced ovarian cancer: an ECOG-ACRIN and NRG GOG study. Gore et al. Multicenter trial of carboplatin/paclitaxel versus oxaliplatin/capecitabine, each with/without bevacizumab, as first line chemotherapy for patients with mucinous epithelial ovarian cancer (mEOC). Bell-McGuinn et al. A phase I study of continuous Veliparib in combination with IV carboplatin/paclitaxel or IV/IP paclitaxel/cisplatin and bevacizumab in newly diagnosed patients with previously untreated epithelial ovarian, fallopian tube, or primary peritoneal cancer: an NRG Oncology/Gynecologic Oncology Group study. Thaker et al. Phase I study of intraperitoneal IL-12 plasmid formulated with PEG-PEI-cholesterol lipopolymer administered in combination with pegylated liposomal doxorubicin in recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal cancer patients: an NRG/GOG study. Dizon et al. Results of a phase I pharmacokinetic study of intraperitoneal bortezomib (B) and carboplatin (C) in patients with persistent or recurrent ovarian cancer (OC): an NRG/Gynecologic Oncology Group study. 7.2. Uterine cancer Atri et al. Utility of PET-CT to evaluate retroperitoneal lymph node metastasis in high risk endometrial cancer. Aghajanian et al. Randomized phase II study of paclitaxel/carboplatin/ bevacizumab (PC + Bev), paclitaxel/carboplatin/temsirolimus (PC + Tem) and ixabepilone/carboplatin/bevacizumab (IC + Bev) as initial therapy for advanced or recurrent endometrial cancer, GOG-0086P: an NRG Oncology/Gynecologic Oncology Group study. Hyman et al. A phase II study of alisertib (MLN8237) in recurrent or persistent uterine leiomyosarcoma: an NRG Oncology/Gynecologic Oncology Group study (GOG-0231D).
Myers et al. Tumor mutational analysis of GOG248, a phase II study of temsirolimus or temsirolimus and alternating megestrol acetate and tamoxifen for advanced endometrial cancer (EC): An NRG Oncology/ Gynecologic Oncology Group study. 7.3. Cervical cancer Ko et al. Impact of older age on chemotherapy, toxicity, and quality of life in women with advanced or recurrent cervical cancer: an NRG Oncology/GOG ancillary study. Atri et al. Utility of PET-CT vs CT alone to evaluate retroperitoneal lymph node metastasis in advanced cervical cancer. Gien et al. Evaluating traditional phase II trial design of systemic therapies in recurrent/advanced cervical cancer: an NRG Oncology/Gynecologic Oncology Group (GOG) ancillary data study. Huh et al. A phase II study of live-attenuated Listeria monocytogenes immunotherapy (ADXS11-001) in the treatment of persistent or recurrent cancer of the cervix (GOG-0265). Chan et al. A phase II evaluation of brivanib in the treatment of persistent or recurrent carcinoma of the cervix: an NRG Oncology/Gynecologic Oncology Group study. Thaker et al. A limited access phase I trial of paclitaxel, cisplatin and ABT-888 in the treatment of advanced, persistent, or recurrent carcinoma of the cervix: an NRG Oncology/Gynecologic Oncology Group study. 8. GOG publications Select recent GOG publications of potential interest are listed as follows. Coleman et al. A phase II evaluation of the potent, highly selective PARP inhibitor Veliparib in the treatment of persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who carry a germline BRCA1 or BRCA2 mutation — an NRG Oncology/ Gynecologic Oncology Group. Gynecol Oncol, 2015. Moore KN, Sill MW, Tenney ME, Darus CJ, Griffin D, Warner T, Rose PG, Behrens R. A phase II trial of trebananib (AMG 386; IND#111,071), a selective angiopoietin 1/2 neutralizing peptibody in patients with persistent/recurrent carcinoma of the endometrium: an NRG Oncology/Gynecologic Oncology Group study. Gynecol Oncol, 2015. McMeekin et al. A phase I study of IV doxorubicin plus intraperitoneal (IP) paclitaxel and IV or IP cisplatin in endometrial cancer patients at high risk for peritoneal failure (GOG9920): an NRG Oncology/ Gynecologic Oncology Group study. Gynecol Oncol, 2015. Chase et al. Factors associated with grade 3–4 treatment-related toxicity in women with advanced or recurrent cervical cancer: an exploratory analysis of Gynecologic Oncology Group trials (GOG) 179 and 204. Int J Gynecol Cancer 2015. 9. What's next? The 2016 Winter NRG Oncology Semi-annual Meeting will be held on January 21–24, 2016 in Atlanta, GA. The Symposium will be held on January 21, 2016 and will be entitled, “Next Generation Immunotherapies for Cancer.” For more information on NRG Oncology, log onto www.nrgoncology. org, and for more information on the GOG Foundation, log onto gog.org. Conflict of interest statement No conflict of interest.
Ronald D. Alvarez University of Alabama, 176F Rm 10250, 619 19th St S, Birmingham, AL 35249-7333, USA E-mail address: [email protected].
Contents lists available at ScienceDirect
Gynecologic Oncology journal homepage: www.elsevier.com/locate/ygyno
Conference Report Report on NRG Oncology and the GOG Foundation
This report will provide an update on NRG Oncology and the GOG Foundation and will review the scientific and educational activities during the NRG Oncology Summer Semi-Annual Meeting in Denver, CO, held on July 16–19, 2015. 1. NRG Oncology. Transitioning from the Gynecologic Oncology Group (GOG), a gynecologic cancer specific cooperative group that existed for nearly 50 years, to the NCTN's NRG Oncology, developed as a result of the NCI's restructuring of their clinical trial program, was not easy. It took a lot of hard work by many dedicated individuals to blend the operational and cultural aspects of three legacy groups (GOG, RTOG, NSABP) and to submit a competitive grant application. As a result of that effort, NRG Oncology has exceeded expectations during its first year of operation. NRG Oncology has accrued more patients to clinical trials and had more new trials approved by the NCI than any of the other three NCTN Operational Centers. The leadership is deeply appreciative of the perseverance and dedication of the countless number of investigators, research staff and employees that made this transition as smooth and successful as possible. Much work remains to ensure the continued success of NRG Oncology but it is off to a great start. 2. GOG Foundation The GOG Foundation is also thriving. The Foundation's Partners Program has completed three pharmaceutical supported trials. Several other trials have recently been activated and more are in development. As the NCI focuses more on smaller biomarker driven trials, these GOG Foundation trials will offer added opportunities for your patients to gain access to cutting edge therapies. Contact the GOG Foundation if you have an interest in participating in these trials. In addition, the GOG Foundation is quite supportive of developing the next generation of gynecologic cancer investigators. The best opportunities to access therapeutic agents in development are to interface with industry's drug development teams. Advisory Boards are often the venue through which the GOG Foundation explores opportunities to bring new therapies from our industry partners into the GOG Foundation's clinical trial portfolio. Young investigators interested in becoming more involved in developing these studies should make it known to the GOG Foundation leadership.
and challenges with development of trials that utilize two or more targeted therapies. Dr. Gwynn Ison from the FDA discussed the regulatory considerations for combinational targeted therapeutics in gynecologic cancer. Other sessions covered examples of active or planned trials investigating the combination of PARP and anti-angiogenic inhibitors, MAPK and PI3K inhibitors, and PD-1 inhibitors and other immunomodulators. These presentations were timely given the number of current combination targeted therapeutic trials for gynecologic cancers recently activated or in development. 4. Ovarian Cancer Trials Speaking of trials, there is now after a longer than desired hiatus an active phase III treatment trial for patients with stage III or IV ovarian cancer. The Partners Program's GOG-3005 trial will evaluate the PARP inhibitor Veliparib in combination with chemotherapy in newly diagnosed patients with high grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer. Eligible patients can be treated after primary debulking or with neoadjuvant chemotherapy. Investigators can choose between dose dense or standard every 3 week paclitaxel to be given in combination with every 3 week carboplatin. Patients will be randomized to either receive chemotherapy alone, chemotherapy with Veliparib, or chemotherapy with Veliparib both during treatment and as a maintenance therapy. The trial will be placebo controlled. Information regarding BRCA mutation status will be assessed on all patients. Other active NCI funded ovarian cancer trials include 1) NRG-CC002, which is conducting perioperative risk assessments in elderly ovarian cancer patients undergoing debulking; 2) GOG-0225, which is evaluating how diet and physical activity can modulate progression free survival in ovarian cancer patients who have completed primary therapy; 3) GOG-0213, which was just amended to accept more patients to evaluate the efficacy of secondary cytoreduction in patients with recurrent ovarian cancer; and 4) NRG-GY003, which is evaluating nivolumab with or without ipilimumab in patients with platinum resistant ovarian cancer. Other important trials are in development and will likely be activated within the year. NRG-GY007, the first of hopefully several trials utilizing the neoadjuvant chemotherapy platform, will investigate ruxolitinib with neoadjuvant chemotherapy in newly diagnosed advanced stage ovarian cancer patients. NRG-GY004 and NRG-GY005 are two trials which will evaluate the PARP inhibitor olaparib and the anti-angiogenic agent cediranib in platinum sensitive and resistant ovarian cancer patients, respectively.
3. Highlights from GOG Foundation's summer semi-annual meeting symposium
5. NCI experimental therapeutic clinical trials network
The Summer Symposium, organized by Dr. John Farley was entitled, “Rational Combination Targeted Therapies for Gynecologic Cancers.” Dr. S. Percy Ivy from the NCI provided an overview of the opportunities
The NCI has changed how it is facilitating development of new investigational drugs. Instead of a mass solicitation for protocol concepts, the NCI will now form a Project Team to draft a preliminary drug,
http://dx.doi.org/10.1016/j.ygyno.2015.08.021
4
Conference Report
biomarker, and assay development plan. The NCI will send out a Request for a Project Team Application and interested investigators with expertise in the investigation drug can apply as either basic, translational, or clinical team members. The participation of young mentored investigation is highly encouraged. The Project Team then proceeds to develop a plan for the investigational agent over a very tight timeline. It is important for those interested in drug development to participate in this new process to help ensure development of clinical trials evaluating exciting new drugs for gynecologic cancers. For more information, contact http://next.cancer.gov. 6. The MATCH Trial NRG Oncology will be participating in the soon to be activated Molecular Analysis for Therapy Choice (MATCH) trial, a part of the President's Precision Medicine Initiative. This phase II trial will enroll 3000 patients with recurrent cancer and use DNA gene sequencing of a tumor biopsy to enroll patients in one of 10 initial treatment arms evaluating drugs that target specific driver mutations. For more information on the MATCH trial, see http://www.cancer.gov/about-cancer/ treatment/clinical-trials/nci-supported/nci-match. 7. ASCO abstract presentations The following select NRG Oncology/GOG Foundation abstracts were presented at the 2015 ASCO Annual Meeting. 7.1. Ovarian cancer Birrer et al. Retrospective analysis of candidate predictive tumor biomarkers (BMs) for efficacy in the GOG-0218 trial evaluating front-line carboplatin-paclitaxel (CP) ± bevacizumab (BEV) for epithelial ovarian cancer (EOC). Lee T et al. CT perfusion as an early biomarker of treatment efficacy in advanced ovarian cancer: an ECOG-ACRIN and NRG GOG study. Gore et al. Multicenter trial of carboplatin/paclitaxel versus oxaliplatin/capecitabine, each with/without bevacizumab, as first line chemotherapy for patients with mucinous epithelial ovarian cancer (mEOC). Bell-McGuinn et al. A phase I study of continuous Veliparib in combination with IV carboplatin/paclitaxel or IV/IP paclitaxel/cisplatin and bevacizumab in newly diagnosed patients with previously untreated epithelial ovarian, fallopian tube, or primary peritoneal cancer: an NRG Oncology/Gynecologic Oncology Group study. Thaker et al. Phase I study of intraperitoneal IL-12 plasmid formulated with PEG-PEI-cholesterol lipopolymer administered in combination with pegylated liposomal doxorubicin in recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal cancer patients: an NRG/GOG study. Dizon et al. Results of a phase I pharmacokinetic study of intraperitoneal bortezomib (B) and carboplatin (C) in patients with persistent or recurrent ovarian cancer (OC): an NRG/Gynecologic Oncology Group study. 7.2. Uterine cancer Atri et al. Utility of PET-CT to evaluate retroperitoneal lymph node metastasis in high risk endometrial cancer. Aghajanian et al. Randomized phase II study of paclitaxel/carboplatin/ bevacizumab (PC + Bev), paclitaxel/carboplatin/temsirolimus (PC + Tem) and ixabepilone/carboplatin/bevacizumab (IC + Bev) as initial therapy for advanced or recurrent endometrial cancer, GOG-0086P: an NRG Oncology/Gynecologic Oncology Group study. Hyman et al. A phase II study of alisertib (MLN8237) in recurrent or persistent uterine leiomyosarcoma: an NRG Oncology/Gynecologic Oncology Group study (GOG-0231D).
Myers et al. Tumor mutational analysis of GOG248, a phase II study of temsirolimus or temsirolimus and alternating megestrol acetate and tamoxifen for advanced endometrial cancer (EC): An NRG Oncology/ Gynecologic Oncology Group study. 7.3. Cervical cancer Ko et al. Impact of older age on chemotherapy, toxicity, and quality of life in women with advanced or recurrent cervical cancer: an NRG Oncology/GOG ancillary study. Atri et al. Utility of PET-CT vs CT alone to evaluate retroperitoneal lymph node metastasis in advanced cervical cancer. Gien et al. Evaluating traditional phase II trial design of systemic therapies in recurrent/advanced cervical cancer: an NRG Oncology/Gynecologic Oncology Group (GOG) ancillary data study. Huh et al. A phase II study of live-attenuated Listeria monocytogenes immunotherapy (ADXS11-001) in the treatment of persistent or recurrent cancer of the cervix (GOG-0265). Chan et al. A phase II evaluation of brivanib in the treatment of persistent or recurrent carcinoma of the cervix: an NRG Oncology/Gynecologic Oncology Group study. Thaker et al. A limited access phase I trial of paclitaxel, cisplatin and ABT-888 in the treatment of advanced, persistent, or recurrent carcinoma of the cervix: an NRG Oncology/Gynecologic Oncology Group study. 8. GOG publications Select recent GOG publications of potential interest are listed as follows. Coleman et al. A phase II evaluation of the potent, highly selective PARP inhibitor Veliparib in the treatment of persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who carry a germline BRCA1 or BRCA2 mutation — an NRG Oncology/ Gynecologic Oncology Group. Gynecol Oncol, 2015. Moore KN, Sill MW, Tenney ME, Darus CJ, Griffin D, Warner T, Rose PG, Behrens R. A phase II trial of trebananib (AMG 386; IND#111,071), a selective angiopoietin 1/2 neutralizing peptibody in patients with persistent/recurrent carcinoma of the endometrium: an NRG Oncology/Gynecologic Oncology Group study. Gynecol Oncol, 2015. McMeekin et al. A phase I study of IV doxorubicin plus intraperitoneal (IP) paclitaxel and IV or IP cisplatin in endometrial cancer patients at high risk for peritoneal failure (GOG9920): an NRG Oncology/ Gynecologic Oncology Group study. Gynecol Oncol, 2015. Chase et al. Factors associated with grade 3–4 treatment-related toxicity in women with advanced or recurrent cervical cancer: an exploratory analysis of Gynecologic Oncology Group trials (GOG) 179 and 204. Int J Gynecol Cancer 2015. 9. What's next? The 2016 Winter NRG Oncology Semi-annual Meeting will be held on January 21–24, 2016 in Atlanta, GA. The Symposium will be held on January 21, 2016 and will be entitled, “Next Generation Immunotherapies for Cancer.” For more information on NRG Oncology, log onto www.nrgoncology. org, and for more information on the GOG Foundation, log onto gog.org. Conflict of interest statement No conflict of interest.
Ronald D. Alvarez University of Alabama, 176F Rm 10250, 619 19th St S, Birmingham, AL 35249-7333, USA E-mail address: [email protected].