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

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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	Not Applicable

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Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	50 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
Study Start Date :	November 2009
Estimated Primary Completion Date :	October 2019
Estimated Study Completion Date :	December 2019

Arms and Interventions

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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

Outcome Measures

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Primary Outcome Measures :

1. percent of mature oocyte yield [ Time Frame: 1-2 month ]
   The percentage of mature oocyte obtained will be compared from both arms.

Eligibility Criteria

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Ages Eligible for Study:	19 Years to 45 Years (Adult)
Sexes 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

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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

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine 

Responsible Party:	Weill Medical College of Cornell University
ClinicalTrials.gov Identifier:	NCT01035099 History of Changes
Other Study ID Numbers:	WCMC-0075
First Posted:	December 18, 2009
Last Update Posted:	May 1, 2017
Last Verified:	April 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

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