PROtecting Ovaries and Fertility During Chemotherapy - The PROOF Trial

NCT ID: NCT00380406

Last Updated: 2017-04-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-01-31
• Study Completion Date: 2010-04-30

Brief Summary

The purpose of this study is to determine whether gonadotropin releasing hormone agonists (medical therapy) will protect against ovarian failure in reproductive aged women undergoing sterilizing chemotherapy.

Detailed Description

Fertility preservation is defined as the maintenance of one's ability to reproduce.

The hypothesis for this study is that medical treatment (GnRHa) will help female cancer patients, receiving sterilizing chemotherapy, preserve their ovarian function and therefore fertility. This study is a feasibility trial of the drug (GnRHa)vs placebo in female cancer patients receiving gonadotoxic chemotherapy between the ages of 18 and 38 who wish to participate.

The objective of the feasibility trial is to determine the feasibility of a definitive study to answer this question and also to define the required parameters needed to design the definitive study such as the observable difference in ovarian failure between the drug and placebo groups. The same protocol will be followed as proposed for the definitive trial but with a smaller sample size.

This pilot study will be conducted at the Ottawa Hospital Regional Cancer Centre/Division of Reproductive Medicine of Department of Obstetrics and Gynecology, University of Ottawa and the Cancer Centre of Southeastern Ontario/Division of Reproductive Medicine of Department of Obstetrics and Gynecology, University of Ottawa.

The planned trial intervention is trimonthly (every 3 months) administration of depot GnRHa (Leuprolide acetate (LA) 11.25 mg intramuscularly) or placebo. Injections would start prior to initiation of chemotherapy, in the luteal phase of the menstrual cycle preceding chemotherapy, and will continue until cessation of chemotherapy (maximum of 6 months or 2 injections). Since only adjuvant/curative chemotherapy patients will be enrolled, chemotherapy will last a maximum of six months.

Subjects will be randomized, with concealed allocation, to either GnRHa or placebo. Subjects and investigators will be blinded to the intervention administered.

Inclusion criteria: Women who are

1. between ages 18 to 38;

2. who will be undergoing gonadotoxic (sterilizing) curative/ adjuvant chemotherapy for early stage disease; and

3. have provided informed consent. All subjects will be enrolled from the Ottawa Hospital Regional Cancer Institute (OHRCC) and the Cancer Center of South Eastern Ontario at Kingston General Hospital (CCSEO). Gonadotoxic chemotherapy includes alkylating / anthracycline agents eg. cyclophosphamide.

Exclusion criteria: Women who;

1. have advanced stage disease and/or whose median survival is expected to be less than 6 months

2. have cancer of the ovaries, uterus, or fallopian tubes;

3. have clinical or biochemical evidence of diminished ovarian reserve (recent shortening of cycles < 24 days between menses, age > 38, elevated serum FSH (follicular stimulating hormone)> 15 IU/L, or low antral follicle count (AFC- number of follicles less than 10 mm on day 2 or 3 of natural menses) on baseline pelvic ultrasound (<5) or elevated day 2 or 3 estradiol (> 280 pmol/ml);

4. have previously received chemotherapy or abdominal/pelvic radiation or have planned to receive abdomino/pelvic radiation;

5. are pregnant;

6. have contraindications to intramuscular injections; or 7) have a history of fractures secondary to/or documented osteoporosis.

Outcomes: Subjects will be assessed at baseline, monthly (for adverse effects only) during active intervention, and at 0, 3, 6, 9, and 12 months post cessation of chemotherapy and treatment (GnRHa/ placebo) for predictors of ovarian reserve.

The primary outcome is protection against ovarian failure at 12 months post chemotherapy. This is measured by resumption of regular menstrual cycles (every 24 -35 days) with documentation of ovulation by biochemistry (progesterone levels) over a minimum of three months.

Secondary outcomes will include sonographic (biophysical) and biochemical markers of ovarian reserve.

Conditions

Fertility Preservation; Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo

Placebo

Group Type: PLACEBO_COMPARATOR

Leuprolide acetate

Intervention Type: DRUG

depot GnRHa (Leuprolide acetate (LA) 11.25 mg intramuscularly)

Group Type: ACTIVE_COMPARATOR

Leuprolide acetate

Intervention Type: DRUG

Interventions

Leuprolide acetate

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Women who are:

1. between ages 18 to 38;

2. who will be undergoing gonadotoxic (sterilizing) curative/ adjuvant chemotherapy for early stage disease; and

3. have provided informed consent. All subjects will be enrolled from the Ottawa Hospital Regional Cancer Institute (OHRCC) and the Cancer Center of South Eastern Ontario at Kingston General Hospital (CCSEO).

Exclusion Criteria

• Women who:

1. have advanced stage disease and/or whose median survival is expected to be less than 6 months

2. have cancer of the ovaries, uterus, or fallopian tubes;

3. have clinical or biochemical evidence of diminished ovarian reserve (recent shortening of cycles < 24 days between menses, age > 38, elevated serum FSH (follicular stimulating hormone)> 15 IU/L, or low antral follicle count (AFC- number of follicles less than 10 mm on day 2 or 3 of natural menses) on baseline pelvic ultrasound (<5) or elevated day 2 or 3 estradiol (> 280 pmol/ml);

4. have previously received chemotherapy or abdominal/pelvic radiation or have planned to receive abdomino/pelvic radiation;

5. are pregnant;

6. have contraindications to intramuscular injections; or

7. have a history of fractures secondary to/or documented osteoporosis.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 38 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University of Ottawa

OTHER

Sponsor Role: collaborator

Queen's University

OTHER

Sponsor Role: collaborator

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

Ottawa Hospital Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sonya Kashyap, MD MSc

Role: PRINCIPAL_INVESTIGATOR

Ottawa Hospital Research Institute

Locations

Cancer Centre of Southeastern Ontario

Kingston, Ontario, Canada

Ottawa Hospital Regional Cancer Centre

Ottawa, Ontario, Canada

Kingston General Hospital

Ottawa, Ontario, Canada

Ottawa Hospital/OHRI

Ottawa, Ontario, Canada

Countries

Canada

Other Identifiers

2006603-01H

Identifier Type: -

Identifier Source: org_study_id