PALBOCICLIB for Breast cancer

Inclusion criteria

• {"criterion_text":"- Previously untreated, histologically confirmed non-inflammatory breast cancer, >4 cm in diameter when evaluated clinically +/- metastatic ipsilateral axillary deposits for which the smallest diameter of the largest node >2 cm by CT or ultrasound scan. For patients with HER2 positive and triple negative breast cancers in Arms E-H the requirement is a tumor size >2 cm, and the tumor must be located so that repeated biopsies can be taken.\n- Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial\n- Before patient registration/randomization, written informed consent must be given according to national and local regulations.\n- For arms B-H: 1) Neutrophils > 1.5 x 109/L, 2) Platelets > 100 x 109/L, 3) Bilirubin < 2 x upper limit normal (ULN). For patients with Gilbert´s syndrome bilirubin >2 x ULN is accepted if there is no evidence of biliary obstruction. 4) Serum creatinine < 1.5 x ULN. 5) ALT and Alk Phos (ALP) <2.5 x ULN\n- WHO performance status 0-1\n- Known tumor ER, PGR, HER2 and TP53 status.\n- Known tumor Ki67 percentage (if ER/PGR>50% and TP53 wt status).\n- Known tumor Ki67 percentage (if ER/PGR>50% and TP53 wt status).\n- Distant metastasis not suspected. Patients will undergo radiology exams during screening phase, after signing the informed consent.\n- Age >18 years\n- Patients must have clinically and/or radiographically documented measurable breast cancer according to RECIST.\n- Radiology studies (CT thorax/abdomen and bone scintigraphy/bone scan) must be performed within 28 days prior to registration."}

Exclusion criteria

• {"criterion_text":"- Unstable angina pectoris or heart failure\n- Other co-morbidity that, based on the assessment of the treating physician, may preclude the use of chemotherapy at actual doses.\n- Pregnant or lactating patients can not be included.\n- Clinical evidence of serious coagulopathy. Prior arterial/venous thrombosis or embolism does not exclude patients from inclusion, unless patient is considered unfit by study oncologist.\n- Patient not able to give an informed consent or comply with study regulations as deemed by study investigator.\n- Active cystitis (to be treated upfront)\n- Active bacterial infections\n- Urinary obstruction"}

Primary endpoints

• {"endpoint_text":"- The primary objective of this trial is to prospectively evaluate the predictive and prognostic value of pre-treatment assessment of a panel of 300 known potential driver mutations in breast cancer by next generation sequencing of tumor DNA.","definition_or_measurement_approach":"Pre-treatment assessment of a panel of 300 known potential driver mutations in breast cancer by next generation sequencing of tumor DNA (i.e. NGS of tumour DNA to evaluate predictive and prognostic value)."}

Secondary endpoints

• {"endpoint_text":"- To assess how genetic/epigenetic disturbances in tumor tissue change during therapy\n- The objective response rate (ORR) of personalized medicine, compared to ORR for best standard-of-care using historical data for comparison.\n- Tumor Ki67 reduction after 2 and 5 weeks of treatment in Arm A.\n- To estimate recurrence-free and overall survival when patients are treated with the optimal personalized treatment available as of 2016, using historical data for comparison.\n- To evaluate the percentage of patients completing neoadjuvant treatment as outlined in Figure 1 and completing surgery.\n- Breast conserving surgery rate (potential to avoid mastectomy).\n- To assess the safety and tolerability of the study treatment given.","definition_or_measurement_approach":"Endpoints measured as described in text: assessment of tumor genetic/epigenetic changes in tumor tissue during therapy (tissue analysis); ORR compared to historical data; Ki67 percentage reduction measured at specified timepoints (2 and 5 weeks) in Arm A; recurrence-free and overall survival compared to historical data; percentage completing neoadjuvant treatment and surgery as per study flow; breast conserving surgery rate; safety and tolerability assessed as study treatment safety outcomes."}

Norway

Earliest CTIS Part Ii Submission Date

21-11-2024

Latest Decision Or Authorization Date

28-11-2024

Processing Time Days

7

Number Of Sites

7

Number Of Participants

200

Primary sponsor

Full Name

Helse Bergen HF

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Norway