AzTrials
AzTrials

Breast CancerPhase 2NCT00954135

Letrozole Plus Oral Cyclophosphamide Plus/Minus Sorafenib as Primary Systemic Treatment in Breast Cancer Patients

A Phase 2 study testing letrozolo+cyclophosphamide and letrozolo+sorafenib+cyclophosphamide in people with Breast Cancer, run by University of Turin, Italy at 2 sites in Italy.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial summary

Endocrine therapy is the mainstay of systemic treatment in patients with endocrine responsive breast cancer. Aromatase inhibitors are the most active agents in post-menopausal women. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer
What is being tested?
letrozolo+cyclophosphamide and letrozolo+sorafenib+cyclophosphamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
190 participants
Where
2 sitesItaly
Study dates
Sep 2007to Dec 2010
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 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 1. Women in postmenopausal status
  • 2. Age> 60 or age > 18 and unfit for chemotherapy with commonly employed regimens in breast cancer patients
  • 3. Diagnosis of invasive BC, T>2, N0-N2, M0,
  • 4. Endocrine Responsive disease according to San Gallen criteria
  • 5. ECOG Performance Status of 0 or 2
  • 6. Life expectancy of at least 12 weeks
Show all 17Show fewer
  • 7. In case of recent surgery, the wound must be completely healed prior to receiving Sorafenib
  • 8. Subjects with at least one uni-dimensional(for RECIST) or bi-dimensional(for WHO) measurable lesion. Lesions must be measured by CT-scan or MRI
  • 9. Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening:
  • 10. Hemoglobin > 9.0 g/dl
  • 11. Absolute neutrophil count (ANC) >1,500/mm3
  • 12. Platelet count 100,000/μl
  • 13. Total bilirubin < 1.5 times the upper limit of normal
  • 14. ALT and AST < 2.5 x upper limit of normal (< 5 x upper limit of normal for patients with liver involvement of their cancer)
  • 15. Alkaline phosphatase < 4 x ULN
  • 16. PT-INR/PTT < 1.5 x upper limit of normal [Patients who are being therapeutically anticoagulated with an agent such as coumadin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists.]
  • 17. Serum creatinine < 1.5 x upper limit of normal.

Who cannot join

  • 1. History of cardiac disease:congestive heart failure >NYHA class 2;active CAD (MI more than 6 mo prior to study entry is allowed); cardiac arrythmias requiring anti-arrythmic therapy( beta blockers or digoxin are permitted) or uncontrolled hypertension.
  • 2. History of HIV infection or chronic hepatitis B or C (This criteria should be modified to allow Hepatitis B or C in protocols looking at HCC patient population).
  • 3. Active clinically serious infections (> grade 2 NCI-CTC version 3.0)
  • 4. Symptomatic metastatic brain or meningeal tumors (unless the patient is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry)
  • 5. Patients with seizure disorder requiring medication (such as steroids or anti-epileptics)
  • 6. History of organ allograft The organ allograft may be allowed as protocol specific.
Show all 9Show fewer
  • 7. Patients with evidence or history of bleeding diathesis
  • 8. Patients undergoing renal dialysis
  • 9. Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors [Ta, Tis \& T1] or any cancer curatively treated > 3 years prior to study entry

Trial locations and contacts

2 sites in 1 country.

Italy2 sites

  • Breast Unit Azienda Ospedaliera Istituti Ospitalieri

    Cremona

  • Azienda Ospedaliera S.Luigi Orbassano

    Orbassano

Other trials in Italy

About this study

Official title: Letrozole Plus Oral Cyclophosphamide Plus/Minus Sorafenib as Primary Systemic Treatment in Post-menopausal, Estrogen Receptor Positive, Breast Cancer Patients

Endocrine therapy is the mainstay of systemic treatment in patients with endocrine responsive breast cancer. Aromatase inhibitors are the most active agents in post-menopausal women. Randomized comparisons either in primary/adjuvant setting or in metastatic disease setting have demonstrated the superiority of these drugs over tamoxifen.

Primary systemic treatment administered to breast cancer patients is a useful model to identify baseline features able to predict which patients are most likely to benefit from cytotoxic treatment and is a way to study new biological markers in relation to the predictive information they provide.

Read more

This treatment modality represents therefore the best way to explore new treatment strategies in particular treatment strategies involving target therapies.

We have conducted a randomised phase II trial in which the activity of Letrozole plus/minus oral metronomic cyclophosphamide as primary systemic treatment has been investigated in a patient population of elderly breast cancer patients. The conclusions were that the combination of letrozole with metronomic cyclophosphamide was a very active scheme. In addition this was the first study demonstrating in vivo the antiangiogenic effect of metronomic scheduling. This study suggests that chemotherapy administered on a metronomic schedule, targeting therefore the neo-angiogenesis, could be synergistic with endocrine therapy with aromatase inhibitors.

Sorafenib is a multi-kinase inhibitor targeting Raf, VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-alfa, Flt-3, c-Kit, and p38.

There is a strong rationale of combining different anti-angiogenic agents. At the ASCO 2007 meeting the data of a phase I study exploring the toxicity of a combination of sorafenib and bevacizumab have been presented. The results showed an increased toxicity being dose limiting in some patients. To our knowledge there are no data un activity and toxicity of adding sorafenib to metronomic chemotherapy.

Read the detailed description

Primary Objective:

To compare the activity of the 2 regimens The primary end point will be the clinical complete response rate of each treatment arm among all registered cases (intent to treat analysis).

Secondary Objectives:

To compare the 2 treatment arms with respect to:

  • Toxicity
  • Progression Free Survival
  • Overall survival

Ancillary studies To evaluate before and after treatment a number of markers of hypoxia, neoangiogenesis, apoptosis, EGFR activating pathways.

Conditions
Breast Cancer
Being tested
letrozolo+cyclophosphamide, letrozolo+sorafenib+cyclophosphamide
Keywords
neoadjuvant therapy, sorafenib, letrozolo, cyclophosphamide
Medical subject headings
Breast Neoplasms

What participants receive

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

  • letrozolo+cyclophosphamideDrug

    Letrozole 2,5 mg/daily + metronomic cyclophosphamide 50 mg/daily for 6 months

  • letrozolo+sorafenib+cyclophosphamideDrug

    Letrozole (2,5 mg/daily) + "metronomic" cyclophosphamide (50 mg/daily) + Sorafenib (400 mg/bid/daily) for 6 months

Study groups in NCT00954135
Study groupRoleWhat they receive
letrozolo+cyclophosphamideActive comparatorNot described
Receives: Drug: letrozolo+cyclophosphamide
letrozolo+sorafenib+cyclophosphamideExperimentalNot described
Receives: Drug: letrozolo+sorafenib+cyclophosphamide

What is being measured

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

  1. Progression free survival

    Measured: six years

Secondary outcomes (1)

  1. Overall survival

    Measured: six years

Timeline

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

  1. First posted7 Aug 2009 (estimated)
  2. Study startSep 2007
  3. Primary completionJun 2010 (estimated)
  4. Study completionDec 2010 (estimated)

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
Single group
Masking
None (open label)
Enrolment
190 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00954135
Sponsor's protocol ID
EudraCT 2007-006208-39
Status last verified
Aug 2009
First submitted
6 Aug 2009
Last updated
7 Aug 2009
Results posted
No
Data monitoring committee
Yes

Publications

  • Bottini A, Generali D, Brizzi MP, Fox SB, Bersiga A, Bonardi S, Allevi G, Aguggini S, Bodini G, Milani M, Dionisio R, Bernardi C, Montruccoli A, Bruzzi P, Harris AL, Dogliotti L, Berruti A. Randomized phase II trial of letrozole and letrozole plus low-dose metronomic oral cyclophosphamide as primary systemic treatment in elderly breast cancer patients. J Clin Oncol. 2006 Aug 1;24(22):3623-8. doi: 10.1200/JCO.2005.04.5773.

    PubMed 16877730

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing letrozolo+cyclophosphamide and letrozolo+sorafenib+cyclophosphamide in people with Breast Cancer, run by University of Turin, Italy at 2 sites in Italy.

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 17 inclusion and 9 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: status not confirmed, as of the sponsor's last update on 7 Aug 2009. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Italy. 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. 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?

Results are not available in the source record.

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?

Progression free survival (time frame: six years). 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 NCT00954135, which also lists 1 linked publication.

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 7 Aug 2009.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in