Approaches to Phase 1 Clinical Trial Design Focused on Safety, Efficiency, and Selected Patient Populations: A Report from the Clinical Trial Design Task Force of the National Cancer Institute Investigational Drug Steering Committee — Clinical Cancer Research

Abstract: Approaches to Phase 1 Clinical Trial Design Focused on Safety, Efficiency, and Selected Patient Populations: A Report from the Clinical Trial Design Task Force of the National Cancer Institute Investigational Drug Steering Committee — Clinical Cancer Research Steering Committee 1. S. Percy Ivy1, 2. Lillian L. Siu2, 3. Elizabeth Garrett-Mayer3 and 4. Larry Rubinstein1 + Author Affiliations 1. Authors' Affiliations:1Investigational Drug Branch and Biometrics Research Branch, Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, Maryland; 2Princess Margaret Hospital, Toronto, Canada; and 3Medical University of South Carolina, Charleston, South Carolina 1. Corresponding Author: S. Percy Ivy, Investigational Drug Branch, Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, 6130 Executive Blvd, Suite 7131, Rockville, MD 20852. Phone: 301-496-1196; Fax: 301-402-0428; E-mail: ivyp@ctep.nci.nih.gov.

Abstract The goals and objectives of phase 1 clinical trials are changing to include further evaluation of endpoints such as molecular targeted effects, in addition to dose-toxicity profile of the investigational agent. Because of these changes in focus, the National Cancer Institute and Investigational Drug Steering Committee's Task Force on Clinical Trial Design met to evaluate the most efficient ways to design and implement early clinical trials with novel therapeutics. Clinical approaches discussed included the conventional 3 + 3 cohort expansion phase 1 design, multi-institutional phase 1 studies, accelerated titration designs, continual reassessment methods, the study of specific target patient populations, and phase 0 studies. Each of these approaches uniquely contributes to some aspect of the phase 1 study, with all focused on dose and schedule determination, patient safety, and limited patient exposure to ineffective doses of investigational agent. The benefit of labor-intensive generation of preliminary biomarker evidence of target inhibition, as well as the value of molecular profiling of the study population, is considered. New drug development is expensive and the failure rate remains high. By identifying patient populations expected to respond to the study agent and tailoring the treatment with a novel drug, investigators will be one step closer to personalizing cancer treatment. The “fail early and fast” approach is acceptable if the appropriate patient population is evaluated in the phase 1 trial. The approaches outlined in this overview address the merits, advantages, disadvantages, and obstacles encountered during first in human studies. Clin Cancer Res; 16(6); 1726–36

Medical News: FDA Reassures on Osteoporosis Drugs - in Endocrinology, Osteoporosis (confused yet?)

FDA Reassures on Osteoporosis Drugs

By John Gever, Senior Editor, MedPage Today Published: March 10, 2010 Reviewed by Zalman S. Agus, MD; Emeritus Professor University of Pennsylvania School of Medicine.

"Bisphosphonate drugs for osteoporosis do not seem to increase the risk of femoral fractures, the FDA announced Wednesday, though the agency will continue to evaluate that possibility. Even as the FDA was making its announcement in Washington, orthopedic surgeons gathered in New Orleans were hearing news of a study showing an eventual decline in bone quality among patients who took bisphosphonates for more than four years. The FDA issued its statement as a result of case reports suggesting that "atypical" subtrochanteric femur fractures were occurring at higher-than-expected rates in women taking bisphosphonate drugs for osteoporosis....."

Breast cancer susceptibility variants alter risks in familial disease -- Latif et al. 47 (2): 126 -- Journal of Medical Genetics

"Conclusions:
This study confirms that susceptibility variants in FGFR2, TOX3 and MAP3K1 and on chromosome 8q are all associated with increased risk of cancer in individuals with a family history of breast cancer, whereas CASP8 is protective in this context. The level of risk is dependent on the strength of the family history and the presence of a BRCA1/2 mutation and contributes to the understanding of the use of these variants in clinical risk prediction."

Medicare Establishes Reimbursement Coverage for Vermillion's OVA1(TM) Test - financial news

"FREMONT, Calif., March 12, 2010 /PRNewswire via COMTEX/ -- Vermillion, Inc. (Pink Sheets: VRML) today announced that Medicare will cover OVA1(TM), a test to help assess the likelihood that an ovarian mass is benign or malignant. Highmark Medicare Services is the CMS contractor that will process Medicare claims for OVA1. Yesterday Highmark announced its decision to cover this new service....."

financial news: short excerpts/overview from article: Avastin- UPDATE 3-Roche's Avastin fails in prostate cancer study (see comments ovarian)

UPDATE 3-Roche's Avastin fails in prostate cancer study
Fri Mar 12, 2010 6:35am EST


* Treatment doesn't prolong life in late stage patients prostate cancer patients (combination therapy phase 111)

* Some adverse effects seen, already noted in other trials

* Follows recent ovarian cancer success and gastric failure

By Martin de Sa'Pinto and Ben Hirschler

"ZURICH/LONDON, March 12 (Reuters) - Roche Holding AG's (ROG.VX) Avastin did not help men with late stage prostate cancer live longer in a clinical trial, marking another setback for the Swiss group as it tries to extend use of the blockbuster drug into new areas.

The miss in prostrate cancer, announced on Friday, follows similar disappointment last month with Avastin in gastric cancer but success in ovarian cancer. (note: GOG trials prior blog postings)