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Metastatic Breast CancerPhase 2ZAMBONEYNCT00811369

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

A Phase 2 study testing Fulvestrant + ZACTIMA in people with Metastatic Breast Cancer, run by Ontario Clinical Oncology Group (OCOG) at 13 sites in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Any age, women only
Conditions the study is for
Metastatic Breast Cancer
What is being tested?
Fulvestrant + ZACTIMA
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
126 participants
Where
13 sitesCanada
Study dates
Aug 2009to Aug 2013
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • Women only
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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
  • Total bilirubin > 1.5 times normal
  • ALT or AST > 2.5 times normal range if no demonstrable liver metastases or > 5 times normal range in the presence of liver metastases. No more than three retests within screening period are allowable.
  • Potassium level outside of normal range, despite supplementation; serum calcium (or ionized or adjusted for albumin), or magnesium below the lower limit of the normal range despite supplementation or creatinine clearance < 30mL/min.
  • History of:
  • Bleeding diathesis (i.e. disseminated intravascular coagulation [DIC], clotting factor deficiency) or
  • Long-term anticoagulant therapy (other than anti-platelet therapy).
  • Any severe concomitant condition which makes it undesirable for the patient to participate in the study or which would jeopardize compliance with the protocol, e.g. severe renal or hepatic impairment or currently unstable or uncompensated respiratory or cardiac conditions, ongoing or active infection, untreated primary hyperparathyroidism, or psychiatric illness that would limit compliance with study requirements.
  • Anticipated life expectancy less than six months.
  • Non-approved/experimental drug treatment within previous 4 weeks before randomization.
  • Significant cardiovascular event (e.g., myocardial infarction, superior vena cava syndrome), New York Heart Association (NYHA) classification of heart disease (Appendix II) > Class II within 3 months before study entry, or presence of cardiac disease that in the opinion of the investigator increases the risk of ventricular arrhythmia.
  • History of arrhythmia (multifocal premature ventricular contractions (PVCs), bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) which is symptomatic or requires treatment (NCI CTCAE Grade 3 or 4) or asymptomatic sustained ventricular tachycardia. Atrial fibrillation, controlled on medication, is not excluded.
  • Congenital long QT syndrome or 1st degree relative with unexplained sudden death under 40 years of age.
  • QT prolongation with other medications that required discontinuation of that medication.
  • Presence of left bundle branch block (LBBB).
  • QTc with Bazett's correction measurable at > 480msec on screening ECG. (Note: If a patient has QTc > 480msec on screening ECG, the screen ECG may be repeated twice (at least 24 hours apart). The average QTc from the three screening ECGs must be < 480msec in order for the patient to be eligible for the study). Patients who are receiving a drug that has a risk of QTc prolongation (see Appendix III, Table 2) are excluded if QTc is > 460msec.
  • Hypertension not controlled by medical therapy (systolic blood pressure > 160 millimeter of mercury (mmHg) or diastolic blood pressure > 100mmHg).
  • Concomitant medications that are potent inducers (rifampicin, rifabutin, phenytoin, carbamazepine, phenobarbital and St. John's Wort) of CYP3A4 function.
  • Not accessible for treatment and follow up.
  • Failure to provide informed consent.

Trial locations and contacts

13 sites in 1 country.

13 sites in 1 country

Canada13 sites

  • Cross Cancer Institute

    Edmonton, Alberta, T6G 1Z2

  • Regional Cancer Program of the Hôpital régional de Sudbury Regional Hospital

    Greater Sudbury, Ontario, P3E 5J1

  • QE II Health Sciences Centre

    Halifax, Nova Scotia, B3H 1V7

  • Juravinski Cancer Centre

    Hamilton, Ontario, L8V 5C2

  • Grand River Regional Cancer Centre

    Kitchener, Ontario, N2G 1G3

  • Centre Hospitalier De L'Universite De Montreal - Hotel Dieu

    Montreal, Quebec, H2W 1T7

  • RSM Durham Regional Cancer Centre

    Oshawa, Ontario, L1G 2B9

  • Ottawa Hospital Cancer Centre

    Ottawa, Ontario, K1H 8L6

  • Saskatoon Cancer Centre

    Saskatoon, Saskatchewan, S7N 4H4

  • Odette Cancer Centre - Sunnybrook Health Sciences Centre

    Toronto, Ontario, M4N 3M5

  • St. Michael's Hospital

    Toronto, Ontario, M5B 1W8

  • Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

  • British Columbia Cancer Agency - Vancouver Centre

    Vancouver, British Columbia, V5Z 4E6

Other trials in Canada

About this study

Official title: A Phase II, Multi-Centre, Randomized, Double-blind Trial to Evaluate the Therapeutic Benefit of Fulvestrant in Combination With ZACTIMA or Fulvestrant Plus Placebo in Postmenopausal Women With Bone Only or Bone Predominant, Hormone Receptor Positive Metastatic Breast Cancer

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.

Read the detailed description

Tumor angiogenesis is associated with invasiveness and the metastatic potential of various cancers. Vascular endothelial growth factor (VEGF), the most potent and specific angiogenic factor, regulates normal and pathologic angiogenesis. The increased expression of VEGF has been correlated with metastases, recurrence and poor prognosis in many cancers. It has been shown the VEGF is involved in osteolysis in women with bone metastases. ZACTIMA is an agent which targets VEGF. ZACTIMA is a new agent with novel method of action - it is a VEGF inhibitor, epidermal growth factor (EGFR) inhibitor, tyrosine kinase inhibitor, as well as a potential RET kinase activity inhibitor.

In summary, women with bone only, or bone predominant, metastatic breast cancer is an ideal group to study anti-angiogenic therapies where angiogenesis could be a major factor in tumor progression and where anti-angiogenic treatment with agents like ZACTIMA could be more effective.

Being tested
Fulvestrant + ZACTIMA, Fulvestrant + Placebo
Keywords
Breast Cancer, Bone Metastases, Telopeptide, Zactima, Fulvestrant
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Fulvestrant + ZACTIMADrug

    Also called Vandetanib

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

  • Fulvestrant + PlaceboDrug

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

Study groups in NCT00811369
Study groupRoleWhat they receive
1ExperimentalFulvestrant + ZACTIMA Group
Receives: Drug: Fulvestrant + ZACTIMA
2Placebo comparatorFulvestrant + Placebo Group
Receives: Drug: Fulvestrant + Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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

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

Secondary outcomes (3)

  1. Progression free survival (PFS)

    Measured: Every 12 weeks until disease progression/recurrence

  2. Response to therapy

    Measured: Every 12 weeks until disease progression/recurrence

  3. Improvement in pain

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Dec 2008 (estimated)
  2. Study startAug 2009
  3. Primary completionOct 2012
  4. Study completionAug 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
126 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00811369
Sponsor's protocol ID
OCOG-2008-ZAMBONEY
Acronym
ZAMBONEY
Status last verified
Nov 2013
First submitted
15 Dec 2008
Last updated
18 Nov 2013
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Fulvestrant + ZACTIMA in people with Metastatic Breast Cancer, run by Ontario Clinical Oncology Group (OCOG) at 13 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Nov 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Significant change in NTx level defined as a ≥ 30% reduction in urinary NTx level from baseline. (time frame: Week # 1-4, 12, and every 12 weeks until disease progression/recurrence). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00811369.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2013.

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