Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

GINECO-EN102b - BKM120 as Monotherapy in the Treatment of Initial or Recurrent Metastatic Endometrial Cancer (ENDOPIK)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
ARCAGY/ GINECO GROUP
ClinicalTrials.gov Identifier:
NCT01397877
First received: July 18, 2011
Last updated: January 14, 2015
Last verified: October 2012
  Purpose

This study is to determine the clinical efficacy of BKM120 as monotherapy in the treatment of initial or recurrent metastatic endometrial cancer after first line radio chemotherapy.

Clinical efficacy will be determined by the non-progression rate at 3 or 2 months depending on the group of patients. The primary endpoint is the non-progression rate at 3 months (12 weeks) for the patient group whose disease is painless (low grade tumor = stratum 1) and the non-progression rate at 2 months (8 weeks) for the group of patients with an aggressive disease (high grade tumor = stratum 2).

Disease progression is defined by the RECIST 1.1 criteria


Condition Intervention Phase
Endometrial Cancer
Drug: BKM120
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 2 Multicenter Study to Assess the Safety and Efficacy of BKM120 as Monotherapy in Treatment of Initial or Recurrent Metastatic Endometrial Cancer After 1st Line Therapy in Patients Who Cannot Undergo Local Surgery and/or Radiotherapy

Further study details as provided by ARCAGY/ GINECO GROUP:

Primary Outcome Measures:
  • Clinical Efficacy [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    To determine the clinical efficacy of BKM120 as monotherapy in the treatment of initial or recurrent metastatic endometrial cancer after first line radio chemotherapy.


Secondary Outcome Measures:
  • Safety according to CTCAE v4.0 criteria and mood questionnaires : PHQ-9 and GAD-7 [ Time Frame: Patient will be followed for the duration of the study, an expected average of 75 days ] [ Designated as safety issue: Yes ]
    To assess patient safety and the tolerance of BKM120 administered as monotherapy at the daily dose of 100 mg.

  • Efficacy: PFS [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    To evaluate progression-free survival

  • Efficacy: ORR [ Time Frame: Patient will be followed for the duration of the study, an expected average of 75 days ] [ Designated as safety issue: No ]
    To evaluate the objective response rate according to RECIST 1.1

  • Efficacy: overall survival [ Time Frame: Patients will be followed for an expected average of 1 year and 75 days ] [ Designated as safety issue: No ]
    To evaluate overall survival.

  • Efficacy: duration of response [ Time Frame: Patients will be followed for an expected average of 1 year and 75 days ] [ Designated as safety issue: No ]

    To evaluate the duration of the response. For patients in complete remission, the duration of the response will be calculated from the day on which a complete response is determined for the first time up to progression.

    For patients in partial remission, the duration of the response will be the overall response period calculated from the administration of the first treatment cycle up to the date of progression.



Estimated Enrollment: 56
Study Start Date: December 2011
Estimated Study Completion Date: September 2016
Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: stratum 1
Patients with low grade disease (grade 1 or 2) with positive or negative mutational status
Drug: BKM120
per os, 60mg/j, until progression or unacceptable toxicity

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Female ≥ 18 years
  • ECOG ≤ 2
  • Histologically confirmed endometrial cancer
  • Not eligible for exclusive curative treatment by surgery and/or radiotherapy
  • Initial metastatic endometrial cancer not treated with chemotherapy or radiotherapy prior to inclusion OR
  • Recurrent endometrial cancer previously treated with adjuvant CT and RT, presenting with a disease-free interval of at least 12 months
  • Presence of one or more measurable lesion(s) outside the irradiated areas
  • Availability at inclusion of samples of tumor tissue (a block or at least 20 unstained slides) for tumor sub-classification and for routine molecular analysis
  • Satisfactory biological functions: PNN ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, hemoglobin ≥ 9.0 g/dL, INR ≤ 2, standard normal values for potassium, calcium and magnesium, serum creatinine ≤ 1.5 x ULN or creatinine clearance > 50 mL/min, ALT and AST within normal range (or ≤ 3.0 x ULN if liver metastases present), Alkaline phosphatase ≤ 2.5 x ULN, serum bilirubin within normal range (or ≤ 1.5 x ULN if liver metastases present; or total bilirubin ≤ 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert Syndrome), fasting glycemia ≤ 120 mg/dL or ≤ 6.7 mmol/L
  • Life expectancy 3 months
  • Post menopausal woman with at least 12 months of natural (spontaneous) amenorrhea
  • Negative serum pregnancy test ≤ 72 hours prior to initiating treatment for woman of child-bearing potential
  • Consent form signed before any procedure performed

Exclusion Criteria:

  • Previous treatment with PI3K inhibitors and/or mTOR
  • Presence of symptomatic CNS metastases. Patient must have completed any prior treatment for CNS metastases ≥ 28 days and, if on corticosteroid therapy, should be receiving a stable low dose
  • Concomitant presence or history of another malignant tumor in the past 3 years prior to inclusion (except spinocellular or cutaneous basal cell epithelioma or non-melanomatous skin cancer treated successfully)
  • Suffering from mood disorders based on an evaluation by the investigator or a psychiatrist OR with a given score according to the PHQ-9 or GAD-7 mood evaluation scale (cf protocol)
  • Concomitant administration of another approved or investigational anticancer agent
  • Pelvic and/or para-aortic radiotherapy within ≤ 28 days prior to inclusion or persistent side effects from this treatment on implementation of the selection procedures
  • Major surgery during the 28 days prior to starting investigational drug or persistent side effects from surgery
  • Uncontrolled diabetes (HbA1c > 8 %)
  • Presence of an active heart disease, especially: LVEF < 50 % determined by MUGA or ECHO, QTc > 480 msec on ECG recorded during selection (with QTcF formula), angina warranting the administration of anti-angina treatment, ventricular arrhythmia except for benign premature ventricular contractions, supraventricular and nodal arrhythmias warranting a pacemaker or not controlled by a treatment, conduction anomalies warranting a pacemaker, valvular disease with documented involvement of cardiac function, symptomatic pericarditis
  • History of heart disease
  • Currently receiving treatment to prolong QT interval accompanied by a known risk of triggering wave burst arrhythmia. Impossible to stop treatment or to replace it before starting study medication
  • GI dysfunction or disease that could significantly interfere with absorption of BKM120
  • Chronic treatment with corticosteroids or other immunosuppressants
  • Any other severe and/or uncontrolled concomitant disease, which is likely to contraindicate the patient's participation
  • Known treatment non-compliance
  • Currently receiving treatment known to be inhibitors or moderate and strong inducers of isoenzyme CYP3A. Impossible to stop this treatment or to replace it with a different treatment before starting the study product
  • Severe pneumonitis
  • Grade ≥ 3 biological anomalies
  • Known history of HIV infection
  • Pregnant woman or nursing mother
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01397877

Locations
France
Clinique Bonnefon
Ales, France
Centre Paul Papin
Angers, France
Institut Ste Catherine
Avignon, France
Hôpital jean Minjoz
Besancon, France
Centre Hospitalier de Blois
Blois, France
Clinique Tivoli
Bordeaux, France
Institut Bergonié
Bordeaux, France
Polyclinique Bordeaux Nord
Bordeaux, France
centre Francois baclesse
Caen, France
Centre jean Perrin
Clermont Ferrand, France
Hôpitaux Civils de Colmar
Colmar, France
Centre Georges François leclerc
Dijon, France
Group Hospitalier Mutualiste de Grenoble
Grenoble, France
Hôpital Michallon - CHU Grenoble
Grenoble, France
CHD Les Oudairies
la Roche sur Yon, France
Hôpital André Mignot
Le Chesnay, France
Centre jean Bernard
Le Mans, France
Centre Oscar Lambret
Lille, France
CHU Dupuytren
Limoges, France
Centre Léon bérard
Lyon, France
institut Paoli Calmette
Marseille, France
Hôpital Prové Clairval
Marseille, France
Groupement de coopération sanitaire
Montpellier, France
CRLC Val d'Aurelle
Montpellier, France, 34298
Centre Alexis Vautrin
Nancy, France
Centre d'oncologie de Gentilly
Nancy, France
Centre Catherine de Sienne
Nantes, France
Centre Antoine Lacassagne
Nice, France
Clinique Valdegour
Nimes, France
CHU Caremeau
Nimes, France
Centre Hospitalier Régional
Orléans, France
Hopital Hotel Dieu
Paris, France, 75004
Hopital Tenon
Paris, France, 75020
Centre Eugene Marquis
Rennes, France
Centre Frederic Joliot
Rouen, France
Centre Henri Becquerel
Rouen, France
Clinique Armoricaine de Radiologie
Saint Brieuc, France
Hôpital rené Huguenin
St Cloud, France
ICO René Gauducheau
St Herblain, France
Centre Etienne DOLET
St Nazaire, France
Institut cancérologuie de la loire
St Priest en Jarez, France
Hôpital Civil
Strasbourg, France
Centre Claudius Régaud
Toulouse, France, 31052
CHU Bretonneau
Tours, France
Institut Gustave Roussy
Villejuif, France
Sponsors and Collaborators
ARCAGY/ GINECO GROUP
Investigators
Principal Investigator: Isabelle Ray-Coquard, MD GINECO - Centre Léon Bérard
  More Information

No publications provided

Responsible Party: ARCAGY/ GINECO GROUP
ClinicalTrials.gov Identifier: NCT01397877     History of Changes
Other Study ID Numbers: ENDOPIK
Study First Received: July 18, 2011
Last Updated: January 14, 2015
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by ARCAGY/ GINECO GROUP:
endometrial cancer
BKM
monotherapy
metastatic
initial treatment

ClinicalTrials.gov processed this record on March 01, 2015