April 1, 2009

IRB Director

Re:INDWaiver Determination for proposed protocol:

Predicting Femara® (Aromatase Inhibitor) Responsiveness in Endometrial Carcinoma

Dear Ms. X

The purpose of this submission is to request a confirmation of my determination that the above noted protocol meets the requirements for exemption from the Investigational New Drug regulations, according to 21 CFR 312.10 I believe the proposed research with Femara®meets the exemption requirements noted in 21 CRF 312.10, specifically:

  1. FEMARA is lawfully marketed in the United Statesby Novartis and has been so since January 2001. See Appendix 1 for Novartis’ current label.
  2. This is an investigator initiated pilot study, please see Study Protocol in Appendix 2. It is not intended to be reported to the FDA as a well-control study in support of the new indication.
  3. This investigator initiated study is not substantial enough to change the current label.
  4. The route of administration and the dose remains the same as currently listed on Femara’s label. Both breast and endometrial cancers have estrogen-dependent forms. Women with endometrial cancer are at increased risk for breast cancer and visa versa. Since the two populations of women overlap in their risk profiles and susceptibility to estrogen driven oncogenesis, it is extremely likely that the consequences of treatment of these populations with aromatase inhibiting agents (e.g. Femara) will be very similar if not indistinguishable. The 2.5 mg oral daily dose of Femara has been well characterized in clinical trials involving breast cancer patients. Similar rates and types of side effects are anticipated in this group of endometrial cancer patients who will receive a 2.5 mg oral daily dosage of Femara.
  5. This study has been approved by the Femara Protocol Review Committee in Novartis. The study protocol has been submitted to the UC Davis Cancer Center Scientific Review Committee and will be submitted to UC Davis IRB before the study will start. UC Davis IRB procedures adhere to the Common Rule regulations and holds the Federalwide Assurance Certificate..
  6. The study participants will not be charged for the costs of drugs in this study and Investigator will not represent in a promotional context that an investigational new drug is safe or effective for the purposes for which it is under investigation or otherwise promote the drug.

Please see section [Reference to UC Davis IRB Consent Risk/Benefit section] for a description of risk/benefit of this study.

Thank you in advance for your attention and consideration of this request.

Sincerely,

Lloyd H. Smith, MD, PhD

Professor and Chair

Department of Obstetrics and Gynecology

University of CaliforniaDavis

4860 Y Street, Suite 2500

Sacramento, CA95817

Attachments:

Appendix 1: Femara Current Label, dated September 2008

Appendix 2: Study Protocol Predicting Aromatase Inhibitor Responsiveness in Endometrial Carcinoma, dated March 19, 2009

Appendix 3: Draft UC Davis IRB Consent Form

Appendix 4: Novartis Letter of Cross-Reference, dated March 9, 2009