EURAMOS-1: A trial of the European and American Osteosarcoma Study Group
Lead Research Organisation:
MRC Clinical Trials Unit
Abstract
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Technical Summary
A randomised trial of the European and American Osteosarcoma Study Group to optimise treatment strategies for patients with resectable osteosarcoma based on histological response to pre-operative chemotherapy.
Osteosarcoma is the most common bone cancer in children, adolescents, and youn adults, but is still a rare disease with an annual incidence of 2-3 million/year. The most common primary sites are the distal femur and proximal tibia, and 15-20% of patients have clinically detectable metastases at the time of diagnosis. The outcome for patients with osteosarcoma was poor before the use of effective chemotherapy, with 2-year overall survival in the region of 15-20%. The administration of multi-agent chemotherapy has dramatically improved the outcome. Most current series report 3-year disease-free survival rates of 60-70% following the administration of pre-operative multi-agent chemotherapy followed by surgical resection and continuation of chemotherapy post-operatively. These positive results, however, apply only to young patients with localised extremity tumours, while other patients - which make up at least one third of all affected individuals - have traditionally been excluded from prospective randomised trials. Judging from case series and cumulative analyses, their outcome is still considerably worse, with survival rates in the order of no more than 20-30% for patients with primary metastatic osteosarcomas or osteosarcomas of the axial skeleton.
Osteosarcoma is the most common bone cancer in children, adolescents, and youn adults, but is still a rare disease with an annual incidence of 2-3 million/year. The most common primary sites are the distal femur and proximal tibia, and 15-20% of patients have clinically detectable metastases at the time of diagnosis. The outcome for patients with osteosarcoma was poor before the use of effective chemotherapy, with 2-year overall survival in the region of 15-20%. The administration of multi-agent chemotherapy has dramatically improved the outcome. Most current series report 3-year disease-free survival rates of 60-70% following the administration of pre-operative multi-agent chemotherapy followed by surgical resection and continuation of chemotherapy post-operatively. These positive results, however, apply only to young patients with localised extremity tumours, while other patients - which make up at least one third of all affected individuals - have traditionally been excluded from prospective randomised trials. Judging from case series and cumulative analyses, their outcome is still considerably worse, with survival rates in the order of no more than 20-30% for patients with primary metastatic osteosarcomas or osteosarcomas of the axial skeleton.
Organisations
- MRC Clinical Trials Unit (Lead Research Organisation)
- National Cancer Institute (NCI) (Collaboration)
- Scandinavian Sarcoma Group (SSG) (Collaboration)
- National Cancer Research Institute (Collaboration)
- Merck (Collaboration)
- European and American Osteosarcoma Study Group (EURAMOS) (Collaboration)
- Cooperative Osteosarcoma Study Group (Collaboration)
People |
ORCID iD |
| Mahesh Parmar (Principal Investigator) |
Publications
Anninga J
(2014)
Workshop report on the 2nd Joint ENCCA/EuroSARC European bone sarcoma network meeting: integration of clinical trials with tumour biology
in Clinical Sarcoma Research
Bielack SS
(2015)
Methotrexate, Doxorubicin, and Cisplatin (MAP) Plus Maintenance Pegylated Interferon Alfa-2b Versus MAP Alone in Patients With Resectable High-Grade Osteosarcoma and Good Histologic Response to Preoperative MAP: First Results of the EURAMOS-1 Good Response Randomized Controlled Trial.
in Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Marina N
(2009)
International collaboration is feasible in trials for rare conditions: the EURAMOS experience.
in Cancer treatment and research
Smeland S
(2019)
Survival and prognosis with osteosarcoma: outcomes in more than 2000 patients in the EURAMOS-1 (European and American Osteosarcoma Study) cohort.
in European journal of cancer (Oxford, England : 1990)
Whelan JS
(2015)
EURAMOS-1, an international randomised study for osteosarcoma: results from pre-randomisation treatment.
in Annals of oncology : official journal of the European Society for Medical Oncology
| Guideline Title | UK guidelines for the management of bone sarcomas |
| Description | British Sarcoma Group: UK guidelines for the management of bone sarcomas (in BMC Clinical Sarcoma Research) |
| Geographic Reach | National |
| Policy Influence Type | Citation in clinical guidelines |
| Impact | Not known |
| URL | https://clinicalsarcomaresearch.biomedcentral.com/articles/10.1186/s13569-016-0047-1 |
| Description | Case study in European Science Foundation EUROCORS programme "Pan-European Clinical Trials" final report |
| Geographic Reach | Europe |
| Policy Influence Type | Citation in other policy documents |
| Description | EURAMOS-1 |
| Geographic Reach | National |
| Policy Influence Type | Participation in a national consultation |
| Description | NICE review of ridaforolimus |
| Geographic Reach | National |
| Policy Influence Type | Participation in a national consultation |
| Impact | Participated in discussions at NICE review |
| Guideline Title | NCCN Clinical Practice Guidelines in Oncology Bone Cancer |
| Description | National Comprehensive Cancer Network - EURAMOS-1 Good Responders |
| Geographic Reach | North America |
| Policy Influence Type | Citation in clinical guidelines |
| Impact | Not known |
| URL | https://emedicine.medscape.com/article/1256857-guidelines |
| Guideline Title | NCCN Clinical Practice Guidelines in Oncology Bone Cancer |
| Description | National Comprehensive Cancer Network - EURAMOS-1 Poor Responders |
| Geographic Reach | North America |
| Policy Influence Type | Citation in clinical guidelines |
| URL | https://emedicine.medscape.com/article/1256857-guidelines |
| Description | Participation in discussions -- EFGCP Multidisciplinary Workshop: A Single CTA in Multinational Clinical Trials - Dream or Option? |
| Geographic Reach | Europe |
| Policy Influence Type | Participation in a national consultation |
| Impact | Led to further ongoing discussions |
| Title | EURAMOS-1 Common Data Set (collated) |
| Description | Collated data from our participating groups in EURAMOS-1 |
| Type Of Material | Improvements to research infrastructure |
| Provided To Others? | No |
| Impact | None yet; pending maturity |
| Title | EURAMOS-1 clinical trial database (EOI data) |
| Description | Database prospectively collecting information on patients who have joined this international clinical trial |
| Type Of Material | Biological samples |
| Provided To Others? | No |
| Impact | ASCO presentation 2013 Papers 2014 to 2015 -- see publications |
| Description | EURAMOS |
| Organisation | Cooperative Osteosarcoma Study Group |
| Country | European Union (EU) |
| Sector | Academic/University |
| PI Contribution | Design, central coordination and analysis of trial data. Discussion, prioritisation and design of further clinical trials from this. New participants to the group are currently joining. |
| Collaborator Contribution | Design and conduct of clinical trials This organisation involves a number of countries. Many of these countries provide money to a central pot. This pot provides money to support the running of the trial, including to MRC CTU. Design and conduct of clinical trials. This trial is a collaboration with the National Cancer Research Network (a component of NIHR and funded by the English Dept of Health) and the corresponding networks in the other UK nations. It specifically includes all the staff at each of the clinical sites that have participated in this clinical trial. Each site identified patients potentially suitable for the trial, sought informed consent, treated and followed-up patients within the trial and provided data through completion and return of case record forms. EURAMOS-1 is run in collaboration with the NCRI bone cancer Clinical Studies Group which, as a group, encourages national participation in trials. Each of the collaborating groups named above includes representatives from a number of countries. In each country, a university is acting as the delegate for many of the MRC's responsibilities as Sponsor. These are not named in detail here but are listed in the EURAMOS-1 European Framework agreement which they have co-signed. Continued provision of free drug (Peg-intron)interferon by Merck for clinical trial use and distribution to trial sites, following their take-over of Schering Plough. |
| Impact | No primary publications yet. Methods and collaboration paper now presented and added as a publication (PMID: 20213400). Invitations to present on high-profile collaboration at international conferences and to EU-level discussions of lessons learned in being the first academic trial to run internationally after the implementation of the EU Clinical Trials Directive (EC\2001\20). 1st results from the good responders randomisation were presented at American Society of Clinical Oncology Annual Meeting 2013 in the oral sarcoma session (and was the only oral presentation on bone sarcoma at the meeting). |
| Description | EURAMOS |
| Organisation | European and American Osteosarcoma Study Group (EURAMOS) |
| Department | European Osteosarcoma Group (EOI) |
| Country | United Kingdom |
| Sector | Charity/Non Profit |
| PI Contribution | Design, central coordination and analysis of trial data. Discussion, prioritisation and design of further clinical trials from this. New participants to the group are currently joining. |
| Collaborator Contribution | Design and conduct of clinical trials This organisation involves a number of countries. Many of these countries provide money to a central pot. This pot provides money to support the running of the trial, including to MRC CTU. Design and conduct of clinical trials. This trial is a collaboration with the National Cancer Research Network (a component of NIHR and funded by the English Dept of Health) and the corresponding networks in the other UK nations. It specifically includes all the staff at each of the clinical sites that have participated in this clinical trial. Each site identified patients potentially suitable for the trial, sought informed consent, treated and followed-up patients within the trial and provided data through completion and return of case record forms. EURAMOS-1 is run in collaboration with the NCRI bone cancer Clinical Studies Group which, as a group, encourages national participation in trials. Each of the collaborating groups named above includes representatives from a number of countries. In each country, a university is acting as the delegate for many of the MRC's responsibilities as Sponsor. These are not named in detail here but are listed in the EURAMOS-1 European Framework agreement which they have co-signed. Continued provision of free drug (Peg-intron)interferon by Merck for clinical trial use and distribution to trial sites, following their take-over of Schering Plough. |
| Impact | No primary publications yet. Methods and collaboration paper now presented and added as a publication (PMID: 20213400). Invitations to present on high-profile collaboration at international conferences and to EU-level discussions of lessons learned in being the first academic trial to run internationally after the implementation of the EU Clinical Trials Directive (EC\2001\20). 1st results from the good responders randomisation were presented at American Society of Clinical Oncology Annual Meeting 2013 in the oral sarcoma session (and was the only oral presentation on bone sarcoma at the meeting). |
| Description | EURAMOS |
| Organisation | Merck |
| Department | Schering Plough |
| Country | United States |
| Sector | Private |
| PI Contribution | Design, central coordination and analysis of trial data. Discussion, prioritisation and design of further clinical trials from this. New participants to the group are currently joining. |
| Collaborator Contribution | Design and conduct of clinical trials This organisation involves a number of countries. Many of these countries provide money to a central pot. This pot provides money to support the running of the trial, including to MRC CTU. Design and conduct of clinical trials. This trial is a collaboration with the National Cancer Research Network (a component of NIHR and funded by the English Dept of Health) and the corresponding networks in the other UK nations. It specifically includes all the staff at each of the clinical sites that have participated in this clinical trial. Each site identified patients potentially suitable for the trial, sought informed consent, treated and followed-up patients within the trial and provided data through completion and return of case record forms. EURAMOS-1 is run in collaboration with the NCRI bone cancer Clinical Studies Group which, as a group, encourages national participation in trials. Each of the collaborating groups named above includes representatives from a number of countries. In each country, a university is acting as the delegate for many of the MRC's responsibilities as Sponsor. These are not named in detail here but are listed in the EURAMOS-1 European Framework agreement which they have co-signed. Continued provision of free drug (Peg-intron)interferon by Merck for clinical trial use and distribution to trial sites, following their take-over of Schering Plough. |
| Impact | No primary publications yet. Methods and collaboration paper now presented and added as a publication (PMID: 20213400). Invitations to present on high-profile collaboration at international conferences and to EU-level discussions of lessons learned in being the first academic trial to run internationally after the implementation of the EU Clinical Trials Directive (EC\2001\20). 1st results from the good responders randomisation were presented at American Society of Clinical Oncology Annual Meeting 2013 in the oral sarcoma session (and was the only oral presentation on bone sarcoma at the meeting). |
| Description | EURAMOS |
| Organisation | Merck |
| Country | Germany |
| Sector | Private |
| PI Contribution | Design, central coordination and analysis of trial data. Discussion, prioritisation and design of further clinical trials from this. New participants to the group are currently joining. |
| Collaborator Contribution | Design and conduct of clinical trials This organisation involves a number of countries. Many of these countries provide money to a central pot. This pot provides money to support the running of the trial, including to MRC CTU. Design and conduct of clinical trials. This trial is a collaboration with the National Cancer Research Network (a component of NIHR and funded by the English Dept of Health) and the corresponding networks in the other UK nations. It specifically includes all the staff at each of the clinical sites that have participated in this clinical trial. Each site identified patients potentially suitable for the trial, sought informed consent, treated and followed-up patients within the trial and provided data through completion and return of case record forms. EURAMOS-1 is run in collaboration with the NCRI bone cancer Clinical Studies Group which, as a group, encourages national participation in trials. Each of the collaborating groups named above includes representatives from a number of countries. In each country, a university is acting as the delegate for many of the MRC's responsibilities as Sponsor. These are not named in detail here but are listed in the EURAMOS-1 European Framework agreement which they have co-signed. Continued provision of free drug (Peg-intron)interferon by Merck for clinical trial use and distribution to trial sites, following their take-over of Schering Plough. |
| Impact | No primary publications yet. Methods and collaboration paper now presented and added as a publication (PMID: 20213400). Invitations to present on high-profile collaboration at international conferences and to EU-level discussions of lessons learned in being the first academic trial to run internationally after the implementation of the EU Clinical Trials Directive (EC\2001\20). 1st results from the good responders randomisation were presented at American Society of Clinical Oncology Annual Meeting 2013 in the oral sarcoma session (and was the only oral presentation on bone sarcoma at the meeting). |
| Description | EURAMOS |
| Organisation | National Cancer Institute (NCI) |
| Department | Children's Oncology Group (COG) |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | Design, central coordination and analysis of trial data. Discussion, prioritisation and design of further clinical trials from this. New participants to the group are currently joining. |
| Collaborator Contribution | Design and conduct of clinical trials This organisation involves a number of countries. Many of these countries provide money to a central pot. This pot provides money to support the running of the trial, including to MRC CTU. Design and conduct of clinical trials. This trial is a collaboration with the National Cancer Research Network (a component of NIHR and funded by the English Dept of Health) and the corresponding networks in the other UK nations. It specifically includes all the staff at each of the clinical sites that have participated in this clinical trial. Each site identified patients potentially suitable for the trial, sought informed consent, treated and followed-up patients within the trial and provided data through completion and return of case record forms. EURAMOS-1 is run in collaboration with the NCRI bone cancer Clinical Studies Group which, as a group, encourages national participation in trials. Each of the collaborating groups named above includes representatives from a number of countries. In each country, a university is acting as the delegate for many of the MRC's responsibilities as Sponsor. These are not named in detail here but are listed in the EURAMOS-1 European Framework agreement which they have co-signed. Continued provision of free drug (Peg-intron)interferon by Merck for clinical trial use and distribution to trial sites, following their take-over of Schering Plough. |
| Impact | No primary publications yet. Methods and collaboration paper now presented and added as a publication (PMID: 20213400). Invitations to present on high-profile collaboration at international conferences and to EU-level discussions of lessons learned in being the first academic trial to run internationally after the implementation of the EU Clinical Trials Directive (EC\2001\20). 1st results from the good responders randomisation were presented at American Society of Clinical Oncology Annual Meeting 2013 in the oral sarcoma session (and was the only oral presentation on bone sarcoma at the meeting). |
| Description | EURAMOS |
| Organisation | National Cancer Research Institute (NCRI) |
| Department | NCRI Bone Cancer CSG |
| Country | United Kingdom |
| Sector | Charity/Non Profit |
| PI Contribution | Design, central coordination and analysis of trial data. Discussion, prioritisation and design of further clinical trials from this. New participants to the group are currently joining. |
| Collaborator Contribution | Design and conduct of clinical trials This organisation involves a number of countries. Many of these countries provide money to a central pot. This pot provides money to support the running of the trial, including to MRC CTU. Design and conduct of clinical trials. This trial is a collaboration with the National Cancer Research Network (a component of NIHR and funded by the English Dept of Health) and the corresponding networks in the other UK nations. It specifically includes all the staff at each of the clinical sites that have participated in this clinical trial. Each site identified patients potentially suitable for the trial, sought informed consent, treated and followed-up patients within the trial and provided data through completion and return of case record forms. EURAMOS-1 is run in collaboration with the NCRI bone cancer Clinical Studies Group which, as a group, encourages national participation in trials. Each of the collaborating groups named above includes representatives from a number of countries. In each country, a university is acting as the delegate for many of the MRC's responsibilities as Sponsor. These are not named in detail here but are listed in the EURAMOS-1 European Framework agreement which they have co-signed. Continued provision of free drug (Peg-intron)interferon by Merck for clinical trial use and distribution to trial sites, following their take-over of Schering Plough. |
| Impact | No primary publications yet. Methods and collaboration paper now presented and added as a publication (PMID: 20213400). Invitations to present on high-profile collaboration at international conferences and to EU-level discussions of lessons learned in being the first academic trial to run internationally after the implementation of the EU Clinical Trials Directive (EC\2001\20). 1st results from the good responders randomisation were presented at American Society of Clinical Oncology Annual Meeting 2013 in the oral sarcoma session (and was the only oral presentation on bone sarcoma at the meeting). |
| Description | EURAMOS |
| Organisation | National Cancer Research Institute (NCRI) |
| Department | National Cancer Research Network (NCRN) |
| Country | United Kingdom |
| Sector | Charity/Non Profit |
| PI Contribution | Design, central coordination and analysis of trial data. Discussion, prioritisation and design of further clinical trials from this. New participants to the group are currently joining. |
| Collaborator Contribution | Design and conduct of clinical trials This organisation involves a number of countries. Many of these countries provide money to a central pot. This pot provides money to support the running of the trial, including to MRC CTU. Design and conduct of clinical trials. This trial is a collaboration with the National Cancer Research Network (a component of NIHR and funded by the English Dept of Health) and the corresponding networks in the other UK nations. It specifically includes all the staff at each of the clinical sites that have participated in this clinical trial. Each site identified patients potentially suitable for the trial, sought informed consent, treated and followed-up patients within the trial and provided data through completion and return of case record forms. EURAMOS-1 is run in collaboration with the NCRI bone cancer Clinical Studies Group which, as a group, encourages national participation in trials. Each of the collaborating groups named above includes representatives from a number of countries. In each country, a university is acting as the delegate for many of the MRC's responsibilities as Sponsor. These are not named in detail here but are listed in the EURAMOS-1 European Framework agreement which they have co-signed. Continued provision of free drug (Peg-intron)interferon by Merck for clinical trial use and distribution to trial sites, following their take-over of Schering Plough. |
| Impact | No primary publications yet. Methods and collaboration paper now presented and added as a publication (PMID: 20213400). Invitations to present on high-profile collaboration at international conferences and to EU-level discussions of lessons learned in being the first academic trial to run internationally after the implementation of the EU Clinical Trials Directive (EC\2001\20). 1st results from the good responders randomisation were presented at American Society of Clinical Oncology Annual Meeting 2013 in the oral sarcoma session (and was the only oral presentation on bone sarcoma at the meeting). |
| Description | EURAMOS |
| Organisation | Scandinavian Sarcoma Group (SSG) |
| Country | Sweden |
| Sector | Charity/Non Profit |
| PI Contribution | Design, central coordination and analysis of trial data. Discussion, prioritisation and design of further clinical trials from this. New participants to the group are currently joining. |
| Collaborator Contribution | Design and conduct of clinical trials This organisation involves a number of countries. Many of these countries provide money to a central pot. This pot provides money to support the running of the trial, including to MRC CTU. Design and conduct of clinical trials. This trial is a collaboration with the National Cancer Research Network (a component of NIHR and funded by the English Dept of Health) and the corresponding networks in the other UK nations. It specifically includes all the staff at each of the clinical sites that have participated in this clinical trial. Each site identified patients potentially suitable for the trial, sought informed consent, treated and followed-up patients within the trial and provided data through completion and return of case record forms. EURAMOS-1 is run in collaboration with the NCRI bone cancer Clinical Studies Group which, as a group, encourages national participation in trials. Each of the collaborating groups named above includes representatives from a number of countries. In each country, a university is acting as the delegate for many of the MRC's responsibilities as Sponsor. These are not named in detail here but are listed in the EURAMOS-1 European Framework agreement which they have co-signed. Continued provision of free drug (Peg-intron)interferon by Merck for clinical trial use and distribution to trial sites, following their take-over of Schering Plough. |
| Impact | No primary publications yet. Methods and collaboration paper now presented and added as a publication (PMID: 20213400). Invitations to present on high-profile collaboration at international conferences and to EU-level discussions of lessons learned in being the first academic trial to run internationally after the implementation of the EU Clinical Trials Directive (EC\2001\20). 1st results from the good responders randomisation were presented at American Society of Clinical Oncology Annual Meeting 2013 in the oral sarcoma session (and was the only oral presentation on bone sarcoma at the meeting). |
| Title | EURAMOS-1 |
| Description | EURAMOS-1 is an international phase 3 trial randomised controlled trial investigating treatment optimisation on the basis of histological response in the adjuvant treatment of osteosarcoma. Primary objectives: 1. To examine, in a randomised controlled trial, whether the addition of ifosfamide and etoposide (IE) to post-operative chemotherapy with cisplatin, doxorubicin and methotrexate improves event-free survival for patients with resectable osteosarcoma and a poor histological response to 10 weeks of pre-operative chemotherapy. 2. To examine, in a randomised controlled trial, whether the addition of interferon-alpha ifn) as maintenance therapy after post-operative chemotherapy with cisplatin, doxorubicin and methotrexate improves event-free survival for patients with resectable osteosarcoma and a good histological response to 10 weeks of pre-operative chemotherapy. Secondary objectives: 3. To investigate whether the addition of IE to post-operative therapy for poor responders, and the addition of ifn as maintenance therapy for good responders, leads to an improvement in overall survival, short-term toxicity, long-term toxicity and quality of life. 4. To investigate whether the addition of IE to post-operative therapy for poor responders, and the addition of ifn as maintenance therapy for good responders, leads to an improvement in event-free and overall survival in patients with localized osteosarcoma at entry. 5. To investigate whether biological or clinical correlates to histological response and outcome can be identified. 6. To establish whether this international cooperation in clinical trials for osteosarcoma is feasible. The trial is currently in follow-up. Results of the primary analysis (for event-free survival) of the good responders randomisation have been presented but active follow-up continues for the poor responders primary outcome measure and all secondary outcome measures. The current principle source of funding for this trial is an MRC Trial Grant. |
| Type | Therapeutic Intervention - Drug |
| Current Stage Of Development | Late clinical evaluation |
| Year Development Stage Completed | 2006 |
| Development Status | Under active development/distribution |
| Clinical Trial? | Yes |
| Impact | 1. Informed EU level policy guidance on research in rare diseases under the EU Clinical Trials Directive. Chief Investigator invited to contribute to European Science Foundation Forward Look on "Investigator Driven Clinical Trials", 2009. 2. Lead to establishment of an expanded collaboration of international research groups (EURAMOS Strategy Group) for the design and implementation of future clinical trials. |
| URL | http://www.euramos.org |
| Description | EURAMOS good responders lay summary |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Participants in your research and patient groups |
| Results and Impact | Lay summary of trial results (First results of the EURAMOS-1: Information for trial participants and families) was prepared and made available via the trial website and sent to investigators to give to participants. Unknown |
| Year(s) Of Engagement Activity | 2013 |
| URL | http://www.euramos.org |
| Description | EURAMOS-1 infographic |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Study participants or study members |
| Results and Impact | We produced an infographic to summarise some of the key EURAMOS-1 results. This was distributed via social media, and to study participants. |
| Year(s) Of Engagement Activity | 2016 |
| URL | http://www.ctu.mrc.ac.uk/news/2016/euramos_results_26082016 |
| Description | Presentation of the EURAMOS-1 Poor Responders randomisation first results |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | Yes |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | First results of this important comparison were presented at international conferences. More presentations will follow in China, UK and Germany, at least, given by the lead investigators. A paper is in development. MAP chemotherapy will the international standard of care. |
| Year(s) Of Engagement Activity | 2014 |
| URL | https://www.ctos.org/PDFs/CTOS%202014%20AM%20FP%20complete%20rfs%20electronic.pdf |