Back to results

Androgen Therapy for Breast Cancer Patients With Aromatase Inhibitor Induced Side-Effects (ART2)

Primary Purpose

Breast Cancer, Arthralgia, Osteoporosis

Status

Unknown status

Phase

Phase 2

Locations

Australia

Study Type

Interventional

Intervention

Testosterone

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring breast, neoplasms, anastrazole, testosterone

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

Provision of written informed consent
Undergone a total mastectomy, a lumpectomy or a quadrantectomy for primary breast cancer +/-chemo, +/-radiotherapy
Have commenced anastrozole therapy within the previous 6 months
Presence of node negative or positive disease
Receptor-positive tumors, defined as ER ≥10% of the tumor cells positive by immunocytochemical evaluation
Postmenopausal whether induced by surgery, radiotherapy (chemotherapy-induced amenorrhea may be difficult to determine they may be amenorrhoeic but still have functioning ovaries), or by being naturally amenorrhoeic, for 1 year or more if younger than 50 and for 6 months if 50 or older
Postmenopausal levels of FSH/LH/E2 (follicle stimulating hormone, luteinizing hormone, oestrogen) according to the definition of "postmenopausal range" for the laboratory involved
Have developed arthralgia and associated joint symptoms whilst being treated with anastrozole with a score of 40mm or greater on a pain and stiffness 100mm VAS
WBC ≥ 3.0 x 109/L, granulocytes ≥ 1.5 X 109/L and platelets ≥ 100 x 109/L.
AST/SGOT or ALT/SGPT ≤ 3 times ULN Serum creatinine ≤ 2 times ULN

Exclusion Criteria:

Presence of metastatic disease
Diabetes mellitus or glucose intolerance defined as a fasting glucose >6mmol/l
Previous or concomitant other (non-breast cancer) malignancy within the previous 5 years
Presence of other non-malignant systemic diseases which may prevent prolonged follow-up
History of coronary artery disease or no history of previous coronary heart disease but at least two other coronary heart disease risk factors: LDL ≥8.8 mg/dL OR if fewer than two other coronary heart disease risk factors: LDL ≥10.45 mg/dL or total fasting cholesterol ≥ 13.2 mg/dL
Patients on hormone replacement therapy (HRT) within 4 weeks before trial treatment was initiated
Patients on breast cancer chemoprevention with anti-oestrogens if less than 18 months between stopping and diagnosis of breast cancer
Are at risk of transmitting Human Immunodeficiency Virus or viral hepatitis via infected blood
Known hypersensitivity to any component of testosterone
Unable to comply with study requirements
Taking the following concomitant medications at the screening visit-bisphosphonate, anti-cancer treatment other than anastrozole (this includes Herceptin).
Prolonged systemic corticosteroid treatment, except for topical applications (e.g. for rash), inhaled sprays (e.g. for obstructive airways diseases), eye drops or local injections (e.g. intra-articular). Note: Short duration (< 2 weeks) of systemic corticosteroids is allowed (e.g. for Chronic Obstructive Pulmonary Disease) but not within 1 month prior to randomisation.
Any investigational drugs
Systemic hormone replacement therapy
Pregnant or lactating women
Patients with history of fragility fracture or low BMD, osteoporosis or osteopenia
Known liver disease

Sites / Locations

Burnside Breast Centre

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Arimidex

Arimidex test 40mg

Arimidex plus test 80mg

Arm Description

Arimidex 1 mg plus placebo

Arimidex 1mg and testosterone 40mg

Arimidex 1mg and testosterone 80mg

Outcomes

Primary Outcome Measures

Reduces arthralgia and associated joint symptoms as indicated by the change in hand or large joint pain from baseline to 3 months using a 100mm visual analogue scale for pain.

Has acceptable safety and tolerability profile with particular reference to androgenic adverse events including acne, hirsutism, and alopecia.

Secondary Outcome Measures

Impacts the bone resorption marker CTx

Impacts serum HDL, LDL Trg, total Chol,

Impacts serum levels of oestrogens, androgens and SHBG levels

Full Information

NCT ID

NCT00497458

First Posted

July 4, 2007

Last Updated

April 7, 2009

Sponsor

Havah Therapeutics Pty Ltd

Collaborators

AstraZeneca

1. Study Identification

Unique Protocol Identification Number

NCT00497458

Brief Title

Androgen Therapy for Breast Cancer Patients With Aromatase Inhibitor Induced Side-Effects

Acronym

ART2

Official Title

Phase II Study of Testosterone Replacement in Women Experiencing Aromatase Inhibitor Side-Effects in Adjuvant Therapy for Breast Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

April 2009

Overall Recruitment Status

Unknown status

Study Start Date

July 2007 (undefined)

Primary Completion Date

April 2009 (Anticipated)

Study Completion Date

June 2009 (Anticipated)

3. Sponsor/Collaborators

Name of the Sponsor

Havah Therapeutics Pty Ltd

Collaborators

AstraZeneca

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this study is to evaluate whether increasing blood levels of androgen can reduce some of the side-effects of anti-estrogen therapy (Arimidex)

Detailed Description

Anastrozole (Arimidex®) is a selective aromatase inhibitor (a drug that interferes with the making of oestrogens). Reduction in serum oestrogen levels in a hormone-receptor positive breast cancer patient is clearly beneficial in delaying the regrowth of breast cancer cells in the body. Anastrozole is effective in reducing serum oestrogen levels which results in several significant side-effects with 2 being of significant importance; joint pain and stiffness and bone thinning or osteoporosis. The question being asked in this trial is if replacement of testosterone to women receiving Anastrozole can have a reduction in these 2 common side-effects. Women normally have circulating in their blood 3 major sex hormones: oestrogen, testosterone and progesterone. Each of these is produced by the ovaries. Oestrogen is also made throughout the body but particularly in body fat. Testosterone can also be made in other parts of the body from hormones (DHEA and DHEAS) that are produced by the adrenal glands. At the time of natural menopause, surgical removal of the ovaries or destruction of the ovaries by chemotherapy, oestrogen and progesterone levels fall precipitously. Testosterone levels however fall more gradually with increasing age such that a woman in her forties has on average only half of the testosterone circulating in her bloodstream as does a woman in her twenties. After a woman has her ovaries removed by surgery or destroyed by chemotherapy testosterone levels can fall by up to fifty percent. However testosterone does not change across menopause, although this varies somewhat between women. Testosterone is known to have many physiological roles in women. Firstly, oestrogen is actually made from testosterone, and without the ability of our bodies to make testosterone we cannot make oestrogen. Testosterone appears to have direct independent effects in different parts of the body, and some women may experience a variety of physical symptoms when their blood levels fall. Anastrazole almost completely blocks the formation of oestrogen from testosterone. Thus the question being asked in this trial is, can increasing the blood level of testosterone reduce specific side-effects caused by reduction availability of hormones in joints and bones.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Breast Cancer, Arthralgia, Osteoporosis

Keywords

breast, neoplasms, anastrazole, testosterone

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

90 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Arimidex

Arm Type

Placebo Comparator

Arm Description

Arimidex 1 mg plus placebo

Arm Title

Arimidex test 40mg

Arm Type

Active Comparator

Arm Description

Arimidex 1mg and testosterone 40mg

Arm Title

Arimidex plus test 80mg

Arm Type

Active Comparator

Arm Description

Arimidex 1mg and testosterone 80mg

Intervention Type

Drug

Intervention Name(s)

Testosterone

Intervention Description

testosterone 40 or 80 mg once a day

Primary Outcome Measure Information:

Title

Reduces arthralgia and associated joint symptoms as indicated by the change in hand or large joint pain from baseline to 3 months using a 100mm visual analogue scale for pain.

Time Frame

3 months

Title

Has acceptable safety and tolerability profile with particular reference to androgenic adverse events including acne, hirsutism, and alopecia.

Time Frame

3 months

Secondary Outcome Measure Information:

Title

Impacts the bone resorption marker CTx

Time Frame

3 months

Title

Impacts serum HDL, LDL Trg, total Chol,

Time Frame

3 months

Title

Impacts serum levels of oestrogens, androgens and SHBG levels

Time Frame

3 months

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Provision of written informed consent Undergone a total mastectomy, a lumpectomy or a quadrantectomy for primary breast cancer +/-chemo, +/-radiotherapy Have commenced anastrozole therapy within the previous 6 months Presence of node negative or positive disease Receptor-positive tumors, defined as ER ≥10% of the tumor cells positive by immunocytochemical evaluation Postmenopausal whether induced by surgery, radiotherapy (chemotherapy-induced amenorrhea may be difficult to determine they may be amenorrhoeic but still have functioning ovaries), or by being naturally amenorrhoeic, for 1 year or more if younger than 50 and for 6 months if 50 or older Postmenopausal levels of FSH/LH/E2 (follicle stimulating hormone, luteinizing hormone, oestrogen) according to the definition of "postmenopausal range" for the laboratory involved Have developed arthralgia and associated joint symptoms whilst being treated with anastrozole with a score of 40mm or greater on a pain and stiffness 100mm VAS WBC ≥ 3.0 x 109/L, granulocytes ≥ 1.5 X 109/L and platelets ≥ 100 x 109/L. AST/SGOT or ALT/SGPT ≤ 3 times ULN Serum creatinine ≤ 2 times ULN Exclusion Criteria: Presence of metastatic disease Diabetes mellitus or glucose intolerance defined as a fasting glucose >6mmol/l Previous or concomitant other (non-breast cancer) malignancy within the previous 5 years Presence of other non-malignant systemic diseases which may prevent prolonged follow-up History of coronary artery disease or no history of previous coronary heart disease but at least two other coronary heart disease risk factors: LDL ≥8.8 mg/dL OR if fewer than two other coronary heart disease risk factors: LDL ≥10.45 mg/dL or total fasting cholesterol ≥ 13.2 mg/dL Patients on hormone replacement therapy (HRT) within 4 weeks before trial treatment was initiated Patients on breast cancer chemoprevention with anti-oestrogens if less than 18 months between stopping and diagnosis of breast cancer Are at risk of transmitting Human Immunodeficiency Virus or viral hepatitis via infected blood Known hypersensitivity to any component of testosterone Unable to comply with study requirements Taking the following concomitant medications at the screening visit-bisphosphonate, anti-cancer treatment other than anastrozole (this includes Herceptin). Prolonged systemic corticosteroid treatment, except for topical applications (e.g. for rash), inhaled sprays (e.g. for obstructive airways diseases), eye drops or local injections (e.g. intra-articular). Note: Short duration (< 2 weeks) of systemic corticosteroids is allowed (e.g. for Chronic Obstructive Pulmonary Disease) but not within 1 month prior to randomisation. Any investigational drugs Systemic hormone replacement therapy Pregnant or lactating women Patients with history of fragility fracture or low BMD, osteoporosis or osteopenia Known liver disease

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Stephen N Birrell, MD PhD

Organizational Affiliation

Havah Therapeutics Pty Ltd

Official's Role

Study Director

Facility Information:

Facility Name

Burnside Breast Centre

City

Adelaide

State/Province

South Australia

Country

Australia

12. IPD Sharing Statement

Learn more about this trial

Androgen Therapy for Breast Cancer Patients With Aromatase Inhibitor Induced Side-Effects

We'll reach out to this number within 24 hrs