RCT of Fixed vs Titrated Letrozole in Breast Cancer Patient Undergoing IVF - Full Text View

Purpose

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	Intervention
Breast Cancer Infertility	Drug: Letrozole


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: 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

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Letrozole

U.S. FDA Resources

Further study details as provided by Weill Medical College of Cornell University:

Primary Outcome Measures:

percent of mature oocyte yield [ Time Frame: 1-2 month ] [ Designated as safety issue: No ]


Estimated Enrollment:	50
Study Start Date:	November 2009
Estimated Study Completion Date:	October 2016
Estimated Primary Completion Date:	October 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

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Eligibility


Ages Eligible for Study:	19 Years to 45 Years (Adult)
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01035099

Contacts


Contact: Eden Rauch, MD	646-962-3327	err9006@med.cornell.edu
Contact: Rodriq Stubbs, NP	646-962-3276	res2011@med.cornell.edu

Locations


United States, New York
Weill Cornell Medical College	Recruiting
New York, New York, United States, 10021
Contact: Eden Rauch, MD 646-962-3327 err9006@med.cornell.edu
Contact: Rodriq Stubbs, NP 646-962-3276 res2011@med.cornell.edu
Principal Investigator: Glenn Schattman, MD

Sponsors and Collaborators

Weill Medical College of Cornell University

Investigators


Principal Investigator:	Glenn Schattman, MD	Weill Cornell Medical Cornell

More Information

Additional Information:

The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine This link exits the ClinicalTrials.gov site


Responsible Party:	Weill Medical College of Cornell University
ClinicalTrials.gov Identifier:	NCT01035099 History of Changes
Other Study ID Numbers:	WCMC-0075
Study First Received:	December 7, 2009
Last Updated:	June 10, 2015
Health Authority:	United States: Food and Drug Administration

Keywords provided by Weill Medical College of Cornell University:


Letrozole IVF (in vitro fertilization) Cryopreservation Fertility Preservation Breast Cancer

Additional relevant MeSH terms:


Breast Neoplasms Infertility Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Genital Diseases, Male Genital Diseases, Female Letrozole	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

ClinicalTrials.gov processed this record on September 27, 2016