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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

9 mei 2016 bijgewerkt door: Sanofi

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.

Studie Overzicht

Toestand

Voltooid

Conditie

Interventie / Behandeling

Studietype

Ingrijpend

Inschrijving (Werkelijk)

42

Fase

  • Fase 2
  • Fase 1

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Spanje
      • Madrid, Spanje, 28041
        • Investigational Site Number 3413
  • Verenigde Staten
    • California
      • Los Angeles, California, Verenigde Staten, 90033
        • Investigational Site Number 1537
    • Florida
      • Fort Meyers, Florida, Verenigde Staten, 33901
        • Investigational Site Number 1238
    • Massachusetts
      • Boston, Massachusetts, Verenigde Staten, 02115
        • Investigational Site Number 1138
    • Michigan
      • Detroit, Michigan, Verenigde Staten, 48201
        • Investigational Site Number 1330
    • New York
      • Bronx, New York, Verenigde Staten, 10467
        • Investigational Site Number 1151
      • New York, New York, Verenigde Staten, 10032
        • Investigational Site Number 1150
    • Tennessee
      • Nashville, Tennessee, Verenigde Staten, 37203
        • Investigational Site Number 1214
      • Nashville, Tennessee, Verenigde Staten, 37232
        • Investigational Site Number 1246

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar en ouder (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Vrouw

Beschrijving

Inclusion Criteria:

  • 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
  • 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

Exclusion Criteria:

  • 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
  • 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

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Niet-gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Arm 1
XL147 in combination with trastuzumab
Geneesmiddel: XL147 (SAR245408)
administered orally once daily as tablet(s)
Biologisch: trastuzumab
administered by IV once every 3 weeks
Andere namen:
  • Herceptin
Experimenteel: Arm 2
XL147 in combination with trastuzumab and paclitaxel
Geneesmiddel: XL147 (SAR245408)
administered orally once daily as tablet(s)
Biologisch: trastuzumab
administered by IV once every 3 weeks
Andere namen:
  • Herceptin
Geneesmiddel: paclitaxel
administered by IV once every week

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Tijdsspanne
Safety and tolerability of XL147 in combination with trastuzumab and in combination with trastuzumab and paclitaxel
Tijdsspanne: safety assessments at weekly study visits
safety assessments at weekly study visits
In Phase 1, the maximum tolerated dose (MTD) of XL147 when administered in combination with trastuzumab and in combination with trastuzumab and paclitaxel
Tijdsspanne: assessed by weekly study visits
assessed by weekly study visits
In Phase 2, objective tumor response
Tijdsspanne: every 6 weeks
every 6 weeks

Secundaire uitkomstmaten

Uitkomstmaat
Tijdsspanne
Duration of response and progression-free survival (Phase 2)
Tijdsspanne: every 6 weeks
every 6 weeks
Pharmacokinetics and pharmacodynamics of XL147 and trastuzumab when given in combination, and of XL147, trastuzumab, and paclitaxel when given in combination
Tijdsspanne: assessed weekly, then every 3 weeks
assessed weekly, then every 3 weeks

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Sanofi

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

1 februari 2010

Primaire voltooiing (Werkelijk)

1 december 2012

Studie voltooiing (Werkelijk)

1 december 2012

Studieregistratiedata

Eerst ingediend

4 januari 2010

Eerst ingediend dat voldeed aan de QC-criteria

5 januari 2010

Eerst geplaatst (Schatting)

6 januari 2010

Updates van studierecords

Laatste update geplaatst (Schatting)

3 juni 2016

Laatste update ingediend die voldeed aan QC-criteria

9 mei 2016

Laatst geverifieerd

1 mei 2016

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • ARD11439
  • XL147-203 (Andere identificatie: (other study code))

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