Trial to Evaluate the Therapeutic Benefit of Fulvestrant in Combination With ZACTIMA in Postmenopausal Women With Bone Predominant, Hormone Receptor Positive Metastatic Breast Cancer

NCT00811369 | Completed Phase 2 DMC

• 1 other identifier: OCOG-2008-ZAMBONEY
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 13

Brief Summary

The purpose of this study is to evaluate whether the combination of fulvestrant and ZACTIMA, versus fulvestrant plus placebo, results in a significant decrease in the bone marker, urinary N-Telopeptide (NTx) in postmenopausal women with bone only, or bone predominant, hormone receptor-positive metastatic breast cancer. A significant decrease will be defined as a \> 30% reduction in urinary NTx level from baseline.

Conditions

Metastatic Breast Cancer

Keywords

Breast Cancer; Bone Metastases; Telopeptide; Zactima; Fulvestrant

Outcome Measures

Primary Outcomes (1)

• Significant change in NTx level defined as a ≥ 30% reduction in urinary NTx level from baseline.

  Week # 1-4, 12, and every 12 weeks until disease progression/recurrence

Secondary Outcomes (3)

• Progression free survival (PFS)

  Every 12 weeks until disease progression/recurrence

• Response to therapy

  Every 12 weeks until disease progression/recurrence

• Improvement in pain

  Week # 1-4, 12, and every 12 weeks until disease progression/recurrence

Study Arms (2)

1

EXPERIMENTAL

Fulvestrant + ZACTIMA Group

Drug: Fulvestrant + ZACTIMA

2

PLACEBO COMPARATOR

Fulvestrant + Placebo Group

Drug: Fulvestrant + Placebo

Interventions

Fulvestrant + ZACTIMA DRUG

ZACTIMA 100 mg tablets. Dose = 1 tablet daily until disease progression or intolerance

Also known as: Vandetanib

1

Fulvestrant + Placebo DRUG

ZACTIMA Placebo 100 mg tablets. Dose = 1 tablet daily for duration of study.

2

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Postmenopausal woman, defined as a woman fulfilling any one of the following criteria:
• Age greater than or equal to 60 years or
• Age greater than or equal to 45 years with amenorrhea more than 12 months with an intact uterus or
• Follicle-stimulating hormone (FSH) levels in postmenopausal range or
• Having undergone a bilateral oophorectomy
• Metastatic breast cancer with either radiologically confirmed bone only or predominant metastases to bone not considered amenable to curative treatment.
• Evidence of hormone sensitivity either ER+ and/or PgR+, as per institutional standards, in the primary tumor.
• Patients must fulfill one of the following RECIST criteria:
• Bone lesions, which are lytic, sclerotic or mixed (lytic + sclerotic), in the absence of measurable disease as defined by RECIST criteria or
• Bone lesions, which are lytic, sclerotic or mixed (lytic + sclerotic), in the presence of measurable disease as defined by RECIST criteria.
• Patients must fulfill one of the following resistances to endocrine therapy criteria:
• Disease progression on tamoxifen or on an aromatase inhibitor as first or second line therapy for metastatic disease or
• Development of metastatic disease while on treatment with tamoxifen or an aromatase inhibitor in the adjuvant setting or
• Disease progression after discontinuation of prior adjuvant endocrine therapy.

You may not qualify if:

• Previous treatment with fulvestrant or ZACTIMA.
• History of hypersensitivity to active or inactive excipients of fulvestrant and/or ZACTIMA.
• Has received greater than one line of systemic chemotherapy for metastatic breast cancer.
• Has received chemotherapy within the past 14 days (+ 2 days).
• Has received radiation therapy within the past 14 days (+ 2 days).
• Has undergone major surgery within the past 21 days or has had major surgery performed \> 21 days prior to screening and the wound remains unhealed.
• Has received LH-RH agonist within the past 4 months.
• Prior treatment with VEGF inhibitors (prior use of AVASTIN permitted).
• Current or previously active systemic malignancy within 3 years prior to randomization (other than breast cancer, or adequately treated in-situ carcinoma of the cervix, uteri, or basal or squamous cell carcinoma of the skin).
• Presence of life-threatening metastatic visceral disease, defined as extensive hepatic involvement, or any degree of brain or leptomeningeal involvement (past or present), or symptomatic pulmonary lymphangetic spread. Patients with discrete pulmonary parenchymal metastases are eligible, provided their respiratory function is not compromised as a result of disease.
• ECOG performance status of \> 2.
• Currently receiving (and are unwilling to discontinue) hormone replacement therapy.
• Laboratory results sustained at:
• Platelets \< 100 x 109 /L
• International normalized ratio (INR) \> 1.6

Sponsors & Collaborators

• Ontario Clinical Oncology Group (OCOG): lead
• AstraZeneca: collaborator

Study Sites (13)

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

British Columbia Cancer Agency - Vancouver Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

QE II Health Sciences Centre

Halifax, Nova Scotia, B3H 1V7, Canada

Location

Regional Cancer Program of the Hôpital régional de Sudbury Regional Hospital

Greater Sudbury, Ontario, P3E 5J1, Canada

Location

Juravinski Cancer Centre

Hamilton, Ontario, L8V 5C2, Canada

Location

Grand River Regional Cancer Centre

Kitchener, Ontario, N2G 1G3, Canada

Location

RSM Durham Regional Cancer Centre

Oshawa, Ontario, L1G 2B9, Canada

Location

Ottawa Hospital Cancer Centre

Ottawa, Ontario, K1H 8L6, Canada

Location

Odette Cancer Centre - Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Centre Hospitalier De L'Universite De Montreal - Hotel Dieu

Montreal, Quebec, H2W 1T7, Canada

Location

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, S7N 4H4, Canada

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Fulvestrant; vandetanib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Mark Clemons, MD

  The Ottawa Hospital Regional Cancer Centre

  PRINCIPAL INVESTIGATOR

• Rebecca Dent, MD

  Odette Cancer Centre - Sunnybrook Health Sciences Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2008
• First Posted: December 19, 2008
• Study Start: August 1, 2009
• Primary Completion: October 1, 2012
• Study Completion: August 1, 2013
• Last Updated: November 18, 2013

Record last verified: 2013-11

Locations

CA (13)