Resumen

Estudio de fase III de capivasertib + paclitaxel versus placebo + paclitaxel como tratamiento de primera línea en pacientes con cáncer de mama triple negativo (TNBC) localmente avanzado o metastásico.

Descripción detallada

Estudio de fase III, doble ciego, aleatorizado, que evalúa la eficacia y seguridad de capivasertib + paclitaxel versus placebo + paclitaxel como tratamiento de primera línea en pacientes con cáncer de mama triple negativo (TNBC) localmente avanzado (inoperable) o metastásico confirmado histológicamente.

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 130 YearsSexo: ALL

Criterios de inclusión

Histologically confirmed TNBC from most recently collected tumour tissue sample
Metastatic or locally recurrent disease; locally recurrent disease most not be amenable to resection with curative intent (patient who are considered suitable for surgical or ablative techniques following potential down-staging with study treatment are not eligible)
ECOG/WHO PS: 0-1
Measurable disease according to RECIST 1.1 and/or lytics or mixedbone lesions that can be assessed by CT or MRI in the absence of measurable disease
FFPE tumour sample from primary/recurrent cancer

Criterios de exclusión

Prior Chemotherapy in the neoadjuvant or adjuvant setting within 6 months from the end of chemotherapy to the date of randomization; taxane chemotherapy in the neoadjuvant or adjuvant setting within 12 months from the end of chemotherapy to the start of randomization
Prior systematic therapy for inoperable locally advanced or metastatic disease
Prior treatment with any of the treatments listed below. Patients are not eligible to enter the study if they have received any of the medications specified below or are unable to meet the cautions and restrictions:
AKT, PI3K, and/or mTOR inhibitors
Capivasertib in the present study (ie, any dosing with capivasertib due to previous participation in this study)
Any other chemotherapy, immunotherapy, immunosuppressant medication (other than corticosteroids) or anticancer agents within 3 weeks of the first dose of study treatment. A longer washout may be required for drugs with a long halflife (eg, biologics) as agreed by the sponsor
Potent inhibitors or inducers of CYP3A4 within 2 weeks prior to the first dose of study treatment (3 weeks for St John's wort), or drugs that are sensitive to CYP3A4 inhibition within 1 week prior to the first dose of study treatment.
Radiotherapy with a wide field of radiation within 4 weeks before the first dose of study treatment (capivasertib/placebo)
Pre-existing sensory or motor polyneuropathy ≥grade 2 according to NCI CTCAE v5
With the exception of alopecia, any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting study treatment
Any of the following cardiac criteria at screening:
Mean resting corrected QT interval (QTc) \>470 msec obtained from 3 consecutive ECGs
Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (eg, complete left bundle branch block, third degree heart block)
Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, potential for Torsades de Pointes, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age or any concomitant medication known to prolong the QT interval
Experience of any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, angina pectoris, congestive heart failure New York Heart Association (NYHA) grade ≥2
Uncontrolled hypotension - SBP \<90 mmHg and/or DBP \<50 mmHg
Cardiac ejection fraction outside institutional range of normal or \<50% (whichever is higher) as measured by echocardiogram (or multiplegated acquisition \[MUGA\] scan if an echocardiogram cannot be performed or is inconclusive).
Clinically significant abnormalities of glucose metabolism as defined by any of the following at screening:
Patients with diabetes mellitus type I or diabetes mellitus type II requiring insulin treatment
HbA1c ≥8.0% (63.9 mmol/mol)
Inadequate bone marrow reserve or organ function at screening
Currently pregnant (confirmed with positive pregnancy test) or breast-feeding

Intervenciones

drug

Capivasertib

400 mg (2 oral tablets) given on an intermittent weekly dosing schedule. Dosed on Days 2 to 5 of Weeks 1, 2, and 3 followed by 1 week off-treatment within each 28-day treatment cycle. Study treatment will be continued until disease progression unless there is evidence of unacceptable toxicity, or if the patient requests to stop the study treatment.

drug

Paclitaxel

80 mg/m2 concentrate for solution for infusion, 3 consecutive weekly infusions of 80 mg/m2 (given on Day 1 of Weeks 1, 2, and 3), followed by 1 week off-treatment within each 28-day treatment cycle. Paclitaxel treatment will be continued for at least 6 cycles unless the patient experiences unacceptable toxicity that is attributed directly to treatment with paclitaxel.

drug

Placebo

Placebo: Oral tablets. 400 mg of Placebo (2 tablets) BD given on an intermittent weekly dosing schedule. Dosed on Days 2 to 5 of Weeks 1, 2, and 3 followed by 1 week offtreatment within each 28-day treatment cycle

Ubicaciones

Research Site

Buenos Aires, Argentina

Research Site

CABA, Argentina

Research Site

CABA, Argentina

Research Site

CABA, Argentina

Research Site

CABA, Argentina

Research Site

Ciudad Autonomade Buenos Aires, Argentina

Research Site

La Plata, Argentina

Research Site

Mar del Plata, Argentina

Research Site

Rosario, Argentina

Estudio de fase III, doble ciego, aleatorizado, que evalúa la eficacia y seguridad de capivasertib + paclitaxel versus placebo + paclitaxel como tratamiento de primera línea en pacientes con cáncer de mama triple negativo localmente avanzado (inoperable) o metastásico (TNBC)

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Capivasertib

Paclitaxel

Placebo

Ubicaciones

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Patrocinadores