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

NCT01035099 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: 0811010075
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer; Infertility

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Mature Oocyte Yield

  Mature oocyte yield in each group

  1 to 2 months

• Percent of Mature Oocyte Yield

  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).

  1 to 2 months

Secondary Outcomes (14)

• Participant Cycle Cancellation Rate

  1 to 2 months

• Breast Cancer Recurrence Rate

  5 years

• Peak Serum Estradiol Level

  1 to 2 months

• FSH ng/ml (Cycle Day 2)

  1 to 2 months

• AMH ng/ml (Cycle Day 2)

  1 to 2 months

Study Arms (2)

Titrated dose Letrozole

EXPERIMENTAL

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

Fixed dose Letrozole

ACTIVE COMPARATOR

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

Interventions

Letrozole DRUG

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;

Also known as: Femara- trade name

Titrated dose Letrozole

Eligibility Criteria

• Age: 19 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead

Study Sites (1)

Weill Cornell Medical College

New York, New York, 10021, United States

Location

Related Links

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

MeSH Terms

Conditions

Breast Neoplasms; Infertility

Interventions

Letrozole

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Genital Diseases; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Rodriq Stubbs
• Organization: Weill Cornell Medicine

res2011@med.cornell.edu

646-962-3276

Study Officials

• Glenn Schattman, MD

  Weill Cornell Medical Cornell

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2009
• First Posted: December 18, 2009
• Study Start: November 1, 2009
• Primary Completion: July 23, 2019
• Study Completion: September 30, 2022
• Last Updated: December 13, 2022
• Results First Posted: July 7, 2020

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)