An interventional study of the combination of BYL719 plus AMG 479 (ganitumab) in adult patients with selected solid tumors
- Conditions
- Solid tumors Hormone receptor positive breast cancerOvarian cancerMedDRA version: 14.1Level: LLTClassification code 10065252Term: Solid tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 14.1Level: PTClassification code 10006187Term: Breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 14.1Level: PTClassification code 10033128Term: Ovarian cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2012-001962-13-ES
- Lead Sponsor
- ovartis Farmaceutica S.A
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 70
1. Written informed consent must be obtained prior to any screening procedures.
2. Patients aged ? 18 years (male or female).
3. Patients with the following histologically/cytologically-confirmed advanced solid tumors with documented somatic PIK3CA mutations or amplifications in tumor tissue (based on available local documentation i.e. pathology report at the site), for whom according to the
assessment of the investigator no standard therapy exists: For dose escalation (phase Ib) only:Hormone receptor positive breast carcinoma, Ovarian carcinoma, Other tumors upon agreement with Novartis
For phase II Arm 1 only: Patients with PIK3CA mutated or amplified hormone receptor positive breast carcinoma
For phase II Arm 2 only: Patients with PIK3CA mutated or amplified ovarian carcinoma
4. Fresh tumor biopsy must be collected at baseline from all patients enrolled to enable the analyses described in the protocol.
5. Patients must have relapsed or progressed following standard therapy or patients for whom no standard anticancer therapy according to investigator assessment exists.
6. Measurable disease as determined by RECIST v1.1. Target lesions in previously irradiated areas should not be selected unless there is clear evidence of progression in such lesions.
7. World Health Organization (WHO)/ Eastern Cooperative Oncology Group (ECOG)) Performance Status (PS) ? 2.
8. Adequate organ function and laboratory parameters as defined by: (ANC) ? 1.5 x 109/L, Hemoglobin (Hgb) ? 9g/dl, Platelets (PLT) ? 100 x 109/L without transfusions within 60 days before first treatment, AST/SGOT and/or ALT/SGPT ? 2.5 x ULN or ? 5 x ULN if liver metastases are present, Serum bilirubin ? 1.5 x ULN, Serum creatinine ? 1.5 x ULN or calculated or directly measured CrCl ? 50% LLN
9. Recovery from all AEs of previous anti-cancer therapies, including surgery and radiotherapy, to baseline or to CTCAE Grade ? 1, except for alopecia.
10. Negative serum pregnancy (?-hCG) test within 72 hrs before starting study treatment in all pre-menopausal women and women < 12 months after the onset of menopause
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 60
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10
1. Prior therapy with PI3Ki- or IGF-1R
2. Patients with known history of severe infusion reactions to monoclonal antibodies.
3. Patients with primary CNS tumor or CNS tumor involvement. However, patients with
metastatic CNS tumors may participate in this study if the patient is: 4 weeks from prior therapy completion (including radiation and/or surgery) and, Clinically stable with respect to the CNS tumor at the time of study entry and, Not receiving steroid therapy and, Not receiving anti-convulsive medications (that were started for brain metastases)
4. Patients who have received prior systemic anti-cancer treatment within the following time frames: Cyclical chemotherapy within a period of time that is shorter than the cycle length used for that treatment (e.g. 6 weeks for nitrosourea, mitomycin-C) prior to starting study treatment, Biologic therapy (e.g. antibodies), continuous or intermittent small molecule therapeutics, or any other investigational agents within a period of time which is ? 5 t1/2 or ? 4 weeks (whichever is shorter) prior to starting study treatment
5. Patients who have received radiotherapy ? 4 weeks prior to starting study drug, with exception of palliative radiotherapy, who have not recovered from side effects of such therapy and/or from whom ? 30% of the bone marrow was irradiated.
6. Patients who have undergone major surgery ? 4 weeks prior to starting study treatment or who have not recovered from side effects of such procedure.
7. History of thromboembolic event requiring full-dose anti-coagulation therapy any time prior to enrollment.
8. Clinically significant cardiac disease or impaired cardiac function, such as: Clinically significant heart disease such as CHF requiring treatment (NYHA Grade ? 2), LVEF < 50% as determined by MUGA scan or echocardiogram (ECHO), or uncontrolled arterial hypertension defined by blood pressure > 140 (systolic) /100 (diastolic) mmHg at rest (average of 3 consecutive readings), History or current evidence of clinically significant cardiac arrhythmias, atrial fibrillation and/or conduction abnormality, e.g. congenital long QT syndrome, high-Grade/complete AV-blockage, History/evidence of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass graft (CABG), coronary angioplasty, or stenting), < 6 months prior to screening, QTcF > 480 msec on screening ECG, Complete left bundle branch block, Right bundle branch block + left anterior hemiblock (bifascicular block)
9. Patients with diabetes mellitus requiring insulin treatment or with fasting plasma glucose ? 125 mg/dL (6.9 mmol/L) and/or HbA1c > 5.9%.
10. Patients with peripheral neuropathy CTCAE Grade ? 2.
11. Patients with diarrhea CTCAE Grade ? 2.
12. Patients with acute or chronic pancreatitis.
13. Any other condition that would, in the Investigator?s judgment, contraindicate patient?s participation in the clinical study due to safety concerns or compliance with clinical study procedures,
14. Impaired GI function or GI disease that may significantly alter the absorption of oral
BYL719
15. Patients who are currently receiving medication with a known risk of prolonging the QT interval or inducing Torsades de Pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug treatment.
16. Patients treated with hematopoietic colony-stimulating growth factors (e.g. G-CSF, GMCSF, M-CSF) ? 2 weeks prior to starting study drug. Erythro
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method