Cancer Drug Approval Endpoints

• General Background Documents
• Multiple Myeloma Endpoints
• Ovarian Cancer Endpoints
• Primary Brain Tumor Endpoints 
• Lung Cancer Endpoints
• Colorectal Cancer Endpoints
• Prostate Cancer Endpoints
• Acute Leukemia Endpoints
• Contact Information

The Food and Drug Administration is undertaking a project to evaluate potential endpoints for cancer drug approval. Endpoints will be examined for the most common cancers, such as lung cancer, colon cancer, etc. For each cancer, FDA will hold public workshops to identify important issues, and these issues will be discussed in meetings of the Oncologic Drugs Advisory Committee (ODAC). Subsequently, guidance documents will be published describing FDA's current thinking on endpoints for cancer drug approval.

Workshop planning will be guided by a steering committee that includes representation from the FDA, the National Cancer Institute, the American Society of Clinical Oncology, and the American Association for Cancer Research. Workshop participants will include oncology experts, radiation oncologists, statisticians, industry representatives, and patient advocates.

Listed below will be agendas, background materials, meeting transcripts, and links providing additional information on workshops and ODAC meetings.

 General Background Documents

• Guidance for Industry: Providing Clinical Evidence of Effectiveness for Human Drug and Biological Products (PDF - 129KB)

• Guidance for Industry: FDA Approval of New Cancer Treatment Uses for Marketed Drug and Biological Products (PDF - 58KB) 

• End Points and United States Food and Drug Administration Approval of Oncology Drugs (PDF - 59KB) From:  Journal of Clinical Oncology 21:1404-1411. © 2003 by American Society of Clinical Oncology. Reprinted with permission from the American Society of Clinical Oncology.

 Multiple Myeloma Endpoints

FDA and the American Society of Hematology (ASH), with co-sponsorship by the American Society of Clinical Oncology (ASCO) and the American Association for Cancer Research (AACR), are holding a public workshop on endpoints for multiple myeloma. Issues identified in the workshop will be further discussed before the Oncologic Drugs Advisory Committee (ODAC) and thereafter will be detailed in FDA Guidance Documents. The meeting will be held on October 26, 2006 in Washington, DC.

• Meeting Information (PDF 14KB)
• Agenda (PDF - 21KB)
• Panelists (PDF - 19KB)
• Presentations
  • Workshop on Clinical Endpoints in Multiple Myloma, Kenneth C. Anderson MD, Dana-Farber Cancer Institute (PDF - 108KB)
  • FDA Approvals in Multiple Myeloma, Anne Farrell, MD, FDA (PDF - 58KB)
  • Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma, Robert A. Kyle MD, Mayo Clinic (PDF - 549KB)
  • Newly Diagnosed Myeloma, S. Vincent Rajkumar MD, Mayo Clinic (PDF - 604KB)
  • Maintenance Therapy, Keith Stewart MD, Mayo Clinic (PDF - 423KB)

 Ovarian Cancer Endpoints

FDA and the American Society of Clinical Oncology (ASCO), with co-sponsorship by the American Association for Cancer Research (AACR), public workshop on endpoints for ovarian cancer, April 26, 2006, 7:30 to 5:00 pm, North Bethesda, Maryland.

• Meeting Information (PDF - 71KB)
• Agenda (PDF - 25KB)
• Meeting Summary (PDF - 289KB)
• Background Information (PDF - 31KB)
• Panelists (PDF - 26KB)
• Questions to the Panel (PDF - 14KB)
• Potential Biomarker and Endpoint Research Priorities (PDF - 14KB)

•  Meeting Presentations

  Regulatory Background (PDF - 80KB)] Lee Pai-Scherf, MD, FDA

  Design Issues in Clinical Trials of Ovarian Cancer

  • Design Issues in Clinical Trials of Ovarian Cancer (PDF - 63KB), Tate Thigpen, University of Mississippi, Presentation

  Regulatory Use of CA-125

  • Use of CA-125 for Response Evaluation in Ovarian Cancer (PDF - 180KB), Robert Bast, MD Anderson Cancer Center and Gordon Rustin, Mt. Vernon Cancer Center, Eng.
  • FDA Perspective: Analytical Aspects of CA Aspects of CA-125 (PDF - 36KB), Robert L. Becker, Jr.  MD, PhD, FDA

  Regulatory Endpoints for First-Time Therapy

  • Is PFS a “valid”surrogate for OS in advanced ovarian cancer? A meta-analysis (PDF - 108KB), Marc Buyse, Institut National du Cancer, Paris, France
  • Clinical Trial Endpoints for Regulatory Approval Regulatory Approval: First First-Line Therapy for Line Therapy for Advanced Ovarian Cancer (PDF - 255KB), Elizabeth Eisenhauer MD, FRCPC
  • First-line therapy in Ovarian Cancer: Surrogate endpoints for accelerated approval (PDF - 244KB), Mark F. Brady, PhD, GOG Statistical and Data Center

  Regulatory Endpoints for Maintenance Therapy

  • Maintenance Therapy in Ovarian Cancer: PFS and OS as Endpoints of Therapeutic Clinical Trials (PDF - 157KB), Robert F. Ozols, MD, PhD, Fox Chase Cancer Center
    David R. Spriggs, MD, Memorial Sloan-Kettering Cancer Center

  Regulatory Endpoints for Subsequent Therapies

  • Endpoints in Ovarian Cancer Clinical Trials: Recurrent Disease (PDF - 158KB), David Spriggs, Memorial Sloan-Kettering Cancer Center

  PROs

  • Patient-Reported Outcomes: End Points for Ovarian Cancer (PDF - 194KB), Lari Wenzel, Ph.D, UC Irvine, and Karen Basen-Engquist, Ph.D. MD Anderson Cancer Center

  NCI Session

  • Biomarker & Endpoint Research Priorities (PDF - 14KB), Edward Trimble MD, MPH, NCI/CTEP

 Primary Brain Tumor Endpoints

AACR/FDA Public Workshop on Clinical Trial End Points in Primary Brain Tumors, January 20, 2006, 8:00 a.m. to 4:00 p.m. North Bethesda, MD 4:00 to 5:00 pm, Optional Session: NCI Research Priorities.

• Meeting Information (PDF - 15KB)
• Background Information (PDF - 30KB)
• Meeting Agenda (PDF - 20KB)
• Questions to the Panel (PDF - 18KB)
• Panelists and Representatives (PDF - 27KB)
• Meeting Information (PDF - 22KB))
• Meeting Summary (PDF - 141KB)
• Meeting Presentations
  
   Overview  
  • Regulatory Background (PDF - 49KB), Edwin Rock, M.D., CDER, FDA
  • Primary Brain Tumors (PDF - 1007KB), Howard A. Fine, MD, National Cancer Institute

  Clinical Trial Endpoints for Approval: Imaging Based Outcomes  

  • Response and Progression-free Survival (PFS) Endpoints for Gliomas, Karla V. Ballman, PhD (Mayo Clinic). Will be posted at a later date.
  • PFS: Is this a Clinically Relevant Endpoint for Clinical Trials Testing Treatments for Malignant Glioma at Time of Progression? Report of Data from the North American Brain Tumor Consortium, Kathleen Lamborn, PhD (University of California - San Francisco).
  • MR Imaging Surrogate Markers of Brain Tumor Therapeutic Response, James M. Provenzale, M.D., Duke University Medical Center
  • PET Scanning with FDG in Brain Tumors – Brain Tumor Measurements in Assessing Responses to Treatment, Nicholas Patronas, MD (NIH)

  Clinical Trial Endpoints for Approval: Patient Reported Outcomes (PROs)  

  • Cognitive Testing and Patient Reported Outcomes in Brain Tumor Clinical Trials (PDF - 40KB), Christina A. Meyers, Ph.D., M. D. Anderson Cancer Center

 Lung Cancer Endpoints

American Society of Clinical Oncology/FDA Lung Cancer Endpoints Workshop (April 15, 2003)

• Background: Guidance for Industry: FDA Requirements for Approval of Drugs to Treat Non-Small Cell Lung Cancer (PDF - 1560KB)  (1991)
• Meeting Agend (PDF - 72KB)
• Executive Summary of Workshop Discussion (PDF- 150KB)
• Workshop Participants (PDF - 97KB)
• Final Summary  (DOC - 163KB)
• Meeting Presentations
  • Requirements for Drug Approval, Regular Approval Endpoints in Oncology (PPT - 113KB), Grant Williams, MD, FDA.
  • Non-Small Cell Lung Cancer Approved First and Second Line Treatment (PPT - 58KB), Martin Cohen, MD, FDA.
  • Endpoints Used Internationally  (PPT - 69KB), Renzo Canetta, MD, Bristol-Myers Squibb.
  • Advanced Non-Small Cell Lung Cancer (PPT - 234KB), David H. Johnson, Vanderbilt University Medical School.
  • Non-Traditional Endpoints in Lung Cancer -  Patient Reported Outcomes (PPT - 792KB) 792, Richard J. Gralla, MD, New York Lung Cancer Alliance.

 Colorectal Cancer Endpoints

FDA Public Workshop on Clinical Trial Endpoints in Colorectal Cancer, November 12, 2003, 8:00 a.m. to 5:00 p.m., Washington DC.

• Colorectal Cancer Endpoints Workshop Summary
• Meeting Announcement
• Meeting Agenda [Word] 
• Workshop Participants (PDF - 97KB)
• FDA Background for Colon Cancer Endpoints Workshop (PDF - 378KB)  
• Colon Cancer Workshop: Questions for Discussion (DOC- 20KB) 
• Meeting Presentations
  • Regulatory Background (PPT - 86KB), Grant Williams, MD, FDA.
  • Design Issues in Colorectal Cancer Trials: Surrogates Endpoints and Non-Inferiority Trials (PPT - 90KB), Thomas R. Fleming, Ph.D., University of Washington.
  • Past FDA Approvals in Colorectal Cancer (PPT - 136KB), Amna Ibrahim M.D, FDA
  • Three Year Disease Free Survival (DFS) vs. Five Year Overall survival (OS) as an Endpoint for Adjuvant Colon Cancer Studies: Data from Randomized Trials (PPT - 245KB, D. Sargent, et. al., Mayo Clinic.
  • Potential Use of Biomarkers or Quality of Life (QoL) Parameters in Colorectal Cancer Drug Approval (PPT - 751KB), Charles D. Blanke, M.D., F.A.C.P., Oregon Health & Science University Cancer Institute.
  • Rectal Cancer Endpoints (PPT - 72KB), Margaret Mooney, National Cancer Institute, NIH.
  • A Case for Time to Tumor Progression as a Clinical Benefit Endpoint in the First-line Therapy of Metastatic Colorectal Cancer (PPT - 1990KB), Langdon L. Miller, MD, PTC Therapeutics.

 Prostate Cancer Endpoints

FDA Public Workshop on Clinical Trial Endpoints in Prostate Cancer, June 21-22, 2004, 8:00 am -5:00 pm, Bethesda, MD  

• Meeting Information (PDF - 135KB)
• Meeting Agenda  
• Questions for Discussion (PDF - 104KB)
• Panelists and Speakers (PDF 106KB)  
• Meeting Presentations 
• Prostate Cancer Endpoints Workshop Summary  (1/13/2005)
  • Monday morning (PDF - 167KB)
  • Monday afternoon (PDF - 87KB)
  • Tuesday morning (PDF - 105KB)

 Acute Leukemia Endpoints

FDA Workshop on Clinical Trial Endpoints in Acute Leukemia, June 24, 2005, 8:30 am – 5:00 pm, Washington, DC

• Meeting Information
• Meeting Agenda
• Workshop Participants
• Meeting Presentations
  • Purpose of Conference and Regulatory Background (PDF 48KB) Nancy Scher, MD; FDA
  • Scope and Background of Panel (PDF - 19KB) Frederick R. Appelbaum, MD; Fred Hutchinson Cancer Research Center
  • Scope of Problem/Heterogeneity Component (PDF - 342KB)
    Frederick R. Appelbaum, MD; Fred Hutchinson Cancer Research Center
  • Definition of Response Component (PDF 127KB) Susan O’Brien, MD; M.D. Anderson Cancer Center
  • Bridge to Transplant Component (PDF - 227KB) Robert J. Arceci, MD, PhD; Johns Hopkins Oncology Center
  • Quality of Life Component (PDF - 34KB)  Philip Breitfeld, MD; Duke University Medical Center
  • Chairs’ Questions to Panel (PDF - 25KB) Frederick R. Appelbaum, MD; Fred Hutchinson Cancer Research Center and Daniel Rosenblum, MD; FDA

 For further information, contact:

Dianne Spillman
Office of Oncology Drug Products (HFD-150),
Center for Drug Evaluation and Research, Food and Drug Administration,
10903 New Hampshire Avenue, Silver Spring MD
Phone: (301) 796-1467
Email: dianne.spillman@fda.hhs.gov