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

This study is currently recruiting participants.
Verified October 2012 by ARCAGY/ GINECO GROUP
Sponsor:
Information provided by (Responsible Party):
ARCAGY/ GINECO GROUP
ClinicalTrials.gov Identifier:
NCT01397877
First received: July 18, 2011
Last updated: January 9, 2014
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

Resource links provided by NLM:


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
Estimated Primary Completion Date: December 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01397877

Contacts
Contact: Virginie Thouviot 01 42 34 83 23 vthouviot@arcagy.org

Locations
France
Clinique Bonnefon Not yet recruiting
Ales, France
Centre Paul Papin Not yet recruiting
Angers, France
Institut Ste Catherine Not yet recruiting
Avignon, France
Hôpital jean Minjoz Not yet recruiting
Besancon, France
Centre Hospitalier de Blois Not yet recruiting
Blois, France
Polyclinique Bordeaux Nord Not yet recruiting
Bordeaux, France
Institut Bergonié Not yet recruiting
Bordeaux, France
Clinique Tivoli Not yet recruiting
Bordeaux, France
centre Francois baclesse Not yet recruiting
Caen, France
Centre jean Perrin Not yet recruiting
Clermont Ferrand, France
Hôpitaux Civils de Colmar Not yet recruiting
Colmar, France
Centre Georges François leclerc Not yet recruiting
Dijon, France
Hôpital Michallon - CHU Grenoble Not yet recruiting
Grenoble, France
Group Hospitalier Mutualiste de Grenoble Not yet recruiting
Grenoble, France
CHD Les Oudairies Not yet recruiting
la Roche sur Yon, France
Hôpital André Mignot Not yet recruiting
Le Chesnay, France
Centre jean Bernard Not yet recruiting
Le Mans, France
Centre Oscar Lambret Not yet recruiting
Lille, France
CHU Dupuytren Not yet recruiting
Limoges, France
Centre Léon bérard Recruiting
Lyon, France
Hôpital Prové Clairval Not yet recruiting
Marseille, France
institut Paoli Calmette Not yet recruiting
Marseille, France
Groupement de coopération sanitaire Not yet recruiting
Montpellier, France
CRLC Val d'Aurelle Not yet recruiting
Montpellier, France, 34298
Contact: Michel FABBRO, physician    04 67 61 30 63      
Principal Investigator: Michel FABBRO, physician         
Centre Alexis Vautrin Not yet recruiting
Nancy, France
Centre d'oncologie de Gentilly Not yet recruiting
Nancy, France
Centre Catherine de Sienne Not yet recruiting
Nantes, France
Centre Antoine Lacassagne Not yet recruiting
Nice, France
Clinique Valdegour Not yet recruiting
Nimes, France
CHU Caremeau Not yet recruiting
Nimes, France
Centre Hospitalier Régional Not yet recruiting
Orléans, France
Hopital Tenon Not yet recruiting
Paris, France, 75020
Contact: Frederic Selle, Dr    +33 1 56 01 60 21    frederic.selle@tnn.ap-hop-paris.fr   
Principal Investigator: Frederic Selle, Dr         
Hopital Hotel Dieu Not yet recruiting
Paris, France, 75004
Principal Investigator: Eric Pujade-Lauraine, MD         
Centre Eugene Marquis Not yet recruiting
Rennes, France
Centre Henri Becquerel Not yet recruiting
Rouen, France
Centre Frederic Joliot Not yet recruiting
Rouen, France
Clinique Armoricaine de Radiologie Not yet recruiting
Saint Brieuc, France
Hôpital rené Huguenin Not yet recruiting
St Cloud, France
ICO René Gauducheau Not yet recruiting
St Herblain, France
Centre Etienne DOLET Not yet recruiting
St Nazaire, France
Institut cancérologuie de la loire Not yet recruiting
St Priest en Jarez, France
Hôpital Civil Not yet recruiting
Strasbourg, France
Centre Claudius Régaud Not yet recruiting
Toulouse, France, 31052
Contact: Laurence GLADIEFF, physician    05 61 42 41 19      
Principal Investigator: Laurence GLADIEFF, physician         
CHU Bretonneau Not yet recruiting
Tours, France
Institut Gustave Roussy Not yet recruiting
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 9, 2014
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

Additional relevant MeSH terms:
Endometrial Neoplasms
Sarcoma, Endometrial Stromal
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Diseases
Genital Diseases, Female
Neoplasms, Complex and Mixed
Neoplasms by Histologic Type
Sarcoma
Neoplasms, Connective and Soft Tissue
Endometrial Stromal Tumors

ClinicalTrials.gov processed this record on April 23, 2014