Try the modernized beta website. Learn more about the modernization effort.
Working… Menu

RCT of Fixed vs Titrated Letrozole in Breast Cancer Patient Undergoing IVF

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01035099
Recruitment Status : Active, not recruiting
First Posted : December 18, 2009
Results First Posted : July 7, 2020
Last Update Posted : November 23, 2021
Information provided by (Responsible Party):
Weill Medical College of Cornell University

Brief Summary:

The purpose of this study is to compare two different ways to administer Letrozole to determine their effectiveness in blocking estrogen production during ovarian stimulation in patients with breast cancer prior to chemotherapy/radiotherapy so that oocytes or embryos can be cryopreserved and patients can possibly achieve a pregnancy after the treatment of breast cancer.

During standard ovulation stimulation, the estrogen levels will exceed normal levels and may reach 10 times the normal level for a 2 week period. This may not be desirable in breast cancer patients. The study hopes to determine if the investigators can stimulate oocyte development in the conventional way and administer different doses of Letrozole as the oocytes develop, to keep estradiol levels low, increase the number of oocytes the investigators are able to recover, and improve the quality of those oocytes.

Condition or disease Intervention/treatment Phase
Breast Cancer Infertility Drug: Letrozole Phase 4

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 41 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Open Label Clinical Trial of Fixed Dose Letrozole vs. Titrated Letrozole for In Vitro Fertilization With Cryopreservation of Oocytes and Embryos in Breast Cancer Patients
Actual Study Start Date : November 2009
Actual Primary Completion Date : July 23, 2019
Estimated Study Completion Date : September 30, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Letrozole

Arm Intervention/treatment
Experimental: Titrated dose Letrozole
Patients who are randomized to the titrated dose of Letrozole, will start gonadotropins in the evening of day #2 of their menstrual cycle with injectable follicle stimulating hormone (FSH) and human menopausal gonadotropin (HMG). Oral Letrozole will be added to the stimulation in the following titrated regimen.
Drug: Letrozole

Letrozole titrated regimen may be started on day 2 of menstrual cycle:

Serum Estradiol level <150 pg/ml- No Letrozole; Serum Estradiol Level 150-250 pg/ml- 2.5mg; Serum Estradiol Level 251-350 pg/ml- 5 mg; Serum Estradiol Level >350 pg/ml - 7.5 mg;

Other Name: Femara- trade name

Active Comparator: Fixed dose Letrozole
Patients who are randomized to fixed dose Letrozole will start Letrozole 5mg daily (orally) on the second day of their menstrual cycle and then gonadotropins on the fourth day of their menstrual cycle.
Drug: Letrozole
Fixed dose of 5 mg per day Letrozole will be started on the second day of their menstrual cycle
Other Name: Femara- trade name

Primary Outcome Measures :
  1. Mature Oocyte Yield [ Time Frame: 1 to 2 months ]
    Mature oocyte yield in each group

  2. Percent of Mature Oocyte Yield [ Time Frame: 1 to 2 months ]
    The percentage of mature oocyte obtained will be compared from both arms. Calculated as number of mature oocytes divided by number of oocytes retrieved (per patient).

Secondary Outcome Measures :
  1. Participant Cycle Cancellation Rate [ Time Frame: 1 to 2 months ]
    Cycle cancellation rate- participant

  2. Breast Cancer Recurrence Rate [ Time Frame: 5 years ]
    5 year follow-up breast cancer recurrence rate

  3. Peak Serum Estradiol Level [ Time Frame: 1 to 2 months ]
    Peak Serum Estradiol Level (pg/ml)

  4. FSH ng/ml (Cycle Day 2) [ Time Frame: 1 to 2 months ]
    FSH ng/ml on Cycle Day 2

  5. AMH ng/ml (Cycle Day 2) [ Time Frame: 1 to 2 months ]
    AMH ng/ml on Cycle Day 2

  6. AF Count [ Time Frame: 1 to 2 months ]
    Antral follicle count

  7. Total Days Stimulation Medications [ Time Frame: 1 to 2 months ]
    Total days of stimulation medications

  8. Total Medication Dose [ Time Frame: 1 to 2 months ]
    Total medication dose given

  9. Total Number of Oocytes [ Time Frame: 1 to 2 months ]
    Total number of oocytes retrieved

  10. Number of Follicles on Day of HCG [ Time Frame: 1 to 2 months ]
    Number of follicles on day of Human Chorionic Gonadotrophin (HCG)

  11. Number of Fertilized Oocytes [ Time Frame: 1 to 2 months ]
    Number of fertilized oocytes among participants

  12. Number of Good Quality Embryos [ Time Frame: 1 to 2 months ]
    Number of good quality embryos among participants

  13. Breast Cancer Recurrence at Year 1-2 [ Time Frame: 1 to 2 years ]
    Number of Subjects with Breast Cancer Recurrence at Year 1-2

  14. Breast Cancer Recurrence at Year 2-3 [ Time Frame: 2- 3 years ]
    Number of Subjects with Breast Cancer Recurrence at year 2-3

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   19 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Female breast cancer patient with breast cancer diagnosis after surgery and before undergoing chemotherapy desiring fertility preservation with oocyte or embryo cryopreservation
  • Healthy subject according to documented medical history and physical examination who has been diagnosed with breast cancer (estrogen and progesterone receptor positive and/or negative)
  • Age less that 45 years at time of informed consent
  • Verbal or written clearance from medical or surgical oncologist to undergo controlled ovarian hyperstimulation-IVF
  • Delay to chemotherapy treatment will not jeopardize cancer treatment outcome
  • Ovarian stimulation will not affect cancer treatment plan
  • Transvaginal ultrasound scan (US) within one month of starting stimulation with no clinically significant pelvic mass
  • Serum FSH level (Day 2-4) less than 25
  • Negative pregnancy test prior to beginning Letrozole or gonadotropin therapy
  • Willing and able to comply with the protocol
  • Voluntary provision of written informed consent, prior to any study related procedure that was not part of normal medical care, with the understanding that the subject can withdraw consent at any time without prejudice to her future medical care
  • Willingness to provide follow-up information on herself and babies born as part of this study

Exclusion Criteria:

  • Patients not medically cleared by their oncologist
  • Patients with stage IV breast cancer based on the poor prognosis, general health of the patient, and higher uncertainty with delaying chemotherapy
  • Any clinically relevant abnormal laboratory value (FSH >25 miu/ml, renal function, (greater than two times normal value), hepatic function (greater than two times normal value), blood biochemistry, hematology (elevated white blood count greater than 1.5 times the normal value, hemoglobin <10mg/dL, thrombocytopenia), abnormal cholesterol profile (total cholesterol ≥ 300mg/dL, abnormal LDL greater than 2 times normal value,) based on a fasting sample during the screening phase
  • Contraindications for the use of gonadotropins (i.e. Tumors other than breast cancer, pregnancy, lactation, undiagnosed vaginal bleeding)
  • Recent or current medical conditions where the patient is not medically stable to undergo stimulation or egg retrieval, HIV infection, diabetes, cardiovascular disease, gastrointestinal, hepatic disease, undiagnosed pelvic mass, renal or pulmonary disease
  • History or presence of alcohol or drug abuse within 12 months of signing consent
  • History of severe allergic or anaphylactic reactions or hypersensitivity to any of the concomitant medication prescribed as part of the treatment regimen in this protocol
  • Administration of investigational drugs within three months prior to signing the informed consent
  • Use of insulin sensitizing agents at least one month prior to signing informed consent
  • Any patient who is not a candidate for IVF

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01035099

Layout table for location information
United States, New York
Weill Cornell Medical College
New York, New York, United States, 10021
Sponsors and Collaborators
Weill Medical College of Cornell University
Layout table for investigator information
Principal Investigator: Glenn Schattman, MD Weill Cornell Medical Cornell
  Study Documents (Full-Text)

Documents provided by Weill Medical College of Cornell University:
Additional Information:
Layout table for additonal information
Responsible Party: Weill Medical College of Cornell University Identifier: NCT01035099    
Other Study ID Numbers: 0811010075
First Posted: December 18, 2009    Key Record Dates
Results First Posted: July 7, 2020
Last Update Posted: November 23, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Weill Medical College of Cornell University:
IVF (in vitro fertilization)
Fertility Preservation
Breast Cancer
Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs