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Breast CancerPhase 1/2NCT01042925

Study of XL147 (SAR245408) in Combination With Trastuzumab or Paclitaxel and Trastuzumab in Subjects With Metastatic Breast Cancer Who Have Progressed on a Previous Trastuzumab-based Regimen

A Phase 1/2 study testing XL147 (SAR245408), trastuzumab and paclitaxel in people with Breast Cancer and Breast Neoplasms, run by Sanofi at 9 sites in 2 countries.

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

Phase 1 of this study will evaluate the maximum tolerated dose (MTD) of XL147 when given in combination with trastuzumab (Herceptin) and in combination with trastuzumab and paclitaxel. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer, Breast Neoplasms
What is being tested?
XL147 (SAR245408), trastuzumab and paclitaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
42 participants
Where
9 sitesin 2 countries
Study dates
Feb 2010to Dec 2012
Phase
Phase 1/2
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

  • The subject has pathologically and radiologically confirmed metastatic HER2 positive breast cancer (Stage IV disease). Subjects must have received and progressed on at least one prior trastuzumab-containing regimen for metastatic disease. For subjects in Arm 2, they must also have received at least one prior taxane-containing regimen.
  • The subject has at least one lesion that is not within a previously radiated field and measurable on computerized tomography (CT) or magnetic resonance imaging scan (MRI)
  • The subjects enrolled in Phase 2 must be willing to undergo a biopsy of the primary tumor or a tumor metastasis at baseline, if tumor tissue is amenable to biopsy
  • The subject's primary tumor and/or metastatic lesion must overexpress HER2
  • For subjects enrolled in Phase 2: samples from archival or fresh tissue, or a tissue block of the subject's tumor.
  • The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
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  • The subject has adequate organ and marrow function
  • The subject is capable of understanding the informed consent and complying with the protocol and has signed the informed consent document prior to any study-specific screening procedures or evaluations being performed.
  • Sexually active subjects must agree to use a medically-accepted barrier method of contraception during the course of the study and for 3 months following discontinuation of study treatments. For subjects using oral contraceptives, a barrier method must be used in addition to the oral contraceptive
  • Subjects of childbearing potential must have a negative pregnancy test at screening and enrollment

Who cannot join

  • The subject has previously been treated with a selective inhibitor of PI3K and / or AKT
  • Certain restrictions on prior therapies apply
  • The subject has not recovered from toxicity due to prior therapy to Grade ≤ 1 or to pre-therapy baseline
  • The subject has untreated, symptomatic, or progressive brain metastases. Any corticosteroid use for brain metastases must have been discontinued without the subsequent appearance of symptoms for ≥4 weeks prior to first study treatment
  • The subject has prothrombin time/International Normalized Ratio (PT/INR) or partial thromboplastin time (PTT) test results at screening that are ≥ 1.3 times above the laboratory upper limit of normal
  • The subject has a diagnosis of uncontrolled diabetes mellitus
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  • The subject has uncontrolled significant intercurrent illness
  • The subject has uncontrolled hypertension or other clinically significant cardiovascular disease
  • The subject has left ventricular ejection fraction (LVEF) ≤ 50%
  • The subject has a baseline corrected QT interval ≥ 460 ms
  • The subject is currently receiving anticoagulation with therapeutic doses of warfarin (low-dose warfarin ≤ 1mg/day is permitted)
  • The subject is pregnant or breastfeeding
  • The subject is known to be positive for the human immunodeficiency virus (HIV) (a test for HIV at screening is not required)
  • The subject has any other diagnosis of malignancy or evidence of malignancy (except non-melanoma skin cancer, in situ carcinoma of the cervix) within 2 years prior to screening for this study
  • The subject has a previously identified allergy or hypersensitivity or is intolerant to components of any of the study treatment formulations
  • The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee

Trial locations and contacts

9 sites in 2 countries.

9 sites in 2 countries

United States8 sites

  • Investigational Site Number 1138

    Boston, Massachusetts, 02115

  • Investigational Site Number 1330

    Detroit, Michigan, 48201

  • Investigational Site Number 1238

    Fort Meyers, Florida, 33901

  • Investigational Site Number 1537

    Los Angeles, California, 90033

  • Investigational Site Number 1214

    Nashville, Tennessee, 37203

  • Investigational Site Number 1246

    Nashville, Tennessee, 37232

  • Investigational Site Number 1150

    New York, New York, 10032

  • Investigational Site Number 1151

    The Bronx, New York, 10467

Other trials in United States

Spain1 site

  • Investigational Site Number 3413

    Madrid, 28041

Other trials in Spain

About this study

Official title: A Phase 1/2 Study of XL147 (SAR245408) Administered in Combination With Trastuzumab or Paclitaxel and Trastuzumab in Subjects With Metastatic Breast Cancer Who Have Progressed on a Previous Trastuzumab-Based Regimen

Phase 1 of this study will evaluate the maximum tolerated dose (MTD) of XL147 when given in combination with trastuzumab (Herceptin) and in combination with trastuzumab and paclitaxel. After the MTD is established for each combination (Phase 2), subjects will be enrolled to evaluate the preliminary efficacy and safety of these combinations in metastatic HER2 positive breast cancer. Both trastuzumab and paclitaxel are used in the treatment of metastatic breast cancer (MBC), but patients can develop resistance.

The link between PI3K mutations and trastuzumab resistance has been seen in breast cancer patients. This suggests that inhibitors of the PI3K/PTEN pathway may have the potential to restore sensitivity to trastuzumab. Similarly, introduction of activated mutant forms of PI3K has been shown to transform and confer paclitaxel resistance to immortalized breast epithelial cells. XL147 is a potent and selective inhibitor of PI3K and inhibits phosphorylation of multiple downstream components of PI3K/PTEN signaling. Therefore, XL147 may have utility in the treatment of trastuzumab resistant/refractory and HER2-positive MBC when administered in combination with trastuzumab alone or with trastuzumab and paclitaxel.

Being tested
XL147 (SAR245408), trastuzumab, paclitaxel
Keywords
HER2 positive breast cancer, breast cancer, breast tumors, human mammary carcinoma
Medical subject headings
Breast Neoplasms

What participants receive

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

  • XL147 (SAR245408)Drug

    administered orally once daily as tablet(s)

  • trastuzumabBiological

    Also called Herceptin

    administered by IV once every 3 weeks

  • paclitaxelDrug

    administered by IV once every week

Study groups in NCT01042925
Study groupRoleWhat they receive
Arm 1ExperimentalXL147 in combination with trastuzumab
Receives: Drug: XL147 (SAR245408); Biological: trastuzumab
Arm 2ExperimentalXL147 in combination with trastuzumab and paclitaxel
Receives: Drug: XL147 (SAR245408); Biological: trastuzumab; Drug: paclitaxel

What is being measured

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

  1. Safety and tolerability of XL147 in combination with trastuzumab and in combination with trastuzumab and paclitaxel

    Measured: safety assessments at weekly study visits

  2. In Phase 1, the maximum tolerated dose (MTD) of XL147 when administered in combination with trastuzumab and in combination with trastuzumab and paclitaxel

    Measured: assessed by weekly study visits

  3. In Phase 2, objective tumor response

    Measured: every 6 weeks

Secondary outcomes (2)

  1. Duration of response and progression-free survival (Phase 2)

    Measured: every 6 weeks

  2. Pharmacokinetics and pharmacodynamics of XL147 and trastuzumab when given in combination, and of XL147, trastuzumab, and paclitaxel when given in combination

    Measured: assessed weekly, then every 3 weeks

Timeline

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

  1. First posted6 Jan 2010 (estimated)
  2. Study startFeb 2010
  3. Primary completionDec 2012
  4. Study completionDec 2012

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
42 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01042925
Sponsor's protocol ID
ARD11439
Other IDs
XL147-203
Status last verified
May 2016
First submitted
4 Jan 2010
Last updated
3 Jun 2016
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing XL147 (SAR245408), trastuzumab and paclitaxel in people with Breast Cancer and Breast Neoplasms, run by Sanofi at 9 sites in 2 countries.

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 10 inclusion and 16 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 3 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States, Spain. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

Safety and tolerability of XL147 in combination with trastuzumab and in combination with trastuzumab and paclitaxel (time frame: safety assessments at weekly study visits). The study lists 3 primary outcomes in all. 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 NCT01042925.

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 3 Jun 2016.

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