PROtecting Ovaries and Fertility During Chemotherapy - The PROOF Trial (PROOF)

April 3, 2017 updated by: Ottawa Hospital Research Institute

PROtecting Ovaries and Fertility During Chemotherapy - The PROOF Trial: A Randomized Controlled Trial of Gonadotropin Releasing Hormone Agonist (GnRHa) for Fertility Preservation in Oncology Patients

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Kingston, Ontario, Canada, K7L 5P9
        • Cancer Centre of Southeastern Ontario
      • Ottawa, Ontario, Canada, K1H 8L6
        • Ottawa Hospital Regional Cancer Centre
      • Ottawa, Ontario, Canada
        • Kingston General Hospital
      • Ottawa, Ontario, Canada
        • Ottawa Hospital/OHRI

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 38 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Drug: Leuprolide acetate
Active Comparator: depot GnRHa (Leuprolide acetate (LA) 11.25 mg intramuscularly)
Drug: Leuprolide acetate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Protection against ovarian failure
Time Frame: 12 months post Chemo therapy
12 months post Chemo therapy

Secondary Outcome Measures

Outcome Measure
Time Frame
Sonographic (biophysical) and biochemical markers of ovarian reserve
Time Frame: 3,6,9,12 months
3,6,9,12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ottawa Hospital Research Institute

Collaborators

Canadian Institutes of Health Research (CIHR)
University of Ottawa
Queen's University

Investigators

  • Principal Investigator: Sonya Kashyap, MD MSc, Ottawa Hospital Research Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2007

Primary Completion (Actual)

January 1, 2010

Study Completion (Actual)

April 1, 2010

Study Registration Dates

First Submitted

September 23, 2006

First Submitted That Met QC Criteria

September 25, 2006

First Posted (Estimate)

September 26, 2006

Study Record Updates

Last Update Posted (Actual)

April 5, 2017

Last Update Submitted That Met QC Criteria

April 3, 2017

Last Verified

August 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2006603-01H

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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