PErsonalized TREatment of High-risk MAmmary Cancer - the PETREMAC Trial

Breast Cancer Clinical Trial

— PETREMAC  

Official title:

PErsonalized TREatment of High-risk MAmmary Cancer - the PETREMAC Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02624973
• Other study ID #: 2015/8463
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: April 15, 2016
• Est. completion date: June 2030

Study information

• Verified date: August 2021
• Source: Haukeland University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Breast cancer is an optimal "model disease" for studying personalized medicine. Breast cancer was the first malignancy for which a predictive factor forecasting response to therapy was identified nearly 50 years ago; the expression of the estrogen receptor (ER). Furthermore, breast cancer is by far the malignancy in which prognostic and predictive factors have been most extensively studied. Primary medical treatment (pre-surgical medical therapy) offers a unique setting to explore predictive factors due to the fact that primary breast cancers are easily accessible to repeated tissue sampling and evaluation of therapy response both clinically and radiologically. For many years, the investigators have studied predictive factors in primary medical treatment of breast cancer. In the present project, the investigators will implement a new trial concept where the current knowledge from previous trials with respect to predictive markers (hormone receptors, HER2; TP53, CHEK2 and RB1), will be combined with massive parallel sequencing (MPS). Thereby, the investigators aim to design the "next-generation" primary medical treatment where 1) therapy regimens are individualized based on a limited number of known predictive factors and, 2) MPS is used to explore additional predictive factors and their co-regulators in order to fully identify the mechanisms of drug sensitivity / resistance across individual tumours and pave the way for further personalized breast cancer therapy in the future. As for the new era of "genomic medicine", the current trial concept will allow individual tumours to be characterized by their unique gene mutation / epigenetic modification profile upfront, to allocate patients to their optimal personalized medicine as compared to "classical" drug testing through phase II/III trials.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 200
• Est. completion date: June 2030
• Est. primary completion date: June 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Previously untreated, histologically confirmed non-inflammatory breast cancer, >4 cm in diameter and /or metastatic ipsilateral axillary deposits for which the smallest diameter of the largest node >2 cm by CT or ultrasound scan.

• WHO performance status 0-1

• Known tumor ER, PGR, HER2 and TP53 status.

• Known tumor Ki67 percentage (if ER/PGR>50% and TP53 wt status).

• Distant metastasis not suspected. Patients will undergo radiology exams during screening phase, after signing the informed consent.

• Age >18 years

• Patients must have clinically and/or radiographically documented measurable breast cancer according to RECIST.

• Radiology studies (CT thorax/abdomen and bone scintigraphy/bone scan) must be performed within 28 days prior to registration.

• 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

• Before patient registration/randomization, written informed consent must be given according to national and local regulations.

• For arms B-H:

• Neutrophils > 1.5 x 109/L

• Platelets > 100 x 109/L

• 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.

• Serum creatinine < 1.5 x ULN

• ALT and Alk Phos (ALP) <2.5 x ULN

• INR < 1.5

Exclusion Criteria:

• Unstable angina pectoris or heart failure

• Other co-morbidity that, based on the assessment of the treating physician, may preclude the use of chemotherapy at actual doses.

• Pregnant or lactating patients can not be included.

• 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.

• Patient not able to give an informed consent or comply with study regulations as deemed by study investigator.

• Active cystitis (to be treated upfront)

• Active bacterial infections

• Urinary obstruction

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Neoadjuvant tamoxifen + goserelin (premenopausal women)

• Neoadjuvant letrozole (postmenopausal women)

• Neoadjuvant endocrine therapy + palbociclib (if lack of response to endocrine therapy alone)

• Neoadjuvant docetaxel + cyclophosphamide

• Neoadjuvant docetaxel

• Neoadjuvant docetaxel + trastuzumab + pertuzumab

• Neoadjuvant docetaxel + cyclophosphamide + trastuzumab + pertuzumab

• Neoadjuvant olaparib

• Neoadjuvant cyclophosphamide (after 10 weeks of olaparib alone)

Procedure:
• Breast conserving surgery or mastectomy + SNB/axillary dissection
After response to neoadjuvant treatment

Radiation:
• Postoperative radiotherapy breast/chest wall + regional lymph nodes

Drug:
• Adjuvant trastuzumab

• Adjuvant letrozole (postmenopausal women)

• Adjuvant tamoxifen + goserelin (premenopausal women)

• Adjuvant palbociclib (if palbociclib given neoadjuvant)

• Adjuvant Epirubicin+ Cyclophosphamide

Locations

Country	Name	City	State
Norway	Haukeland University Hospital	Bergen	Hordaland
Norway	Helse Førde	Førde	Sogn Og Fjordande
Norway	Helse Fonna	Haugesund	Rogaland
Norway	Akershus University Hospital	Lørenskog	Akershus
Norway	Helse Stavanger	Stavanger	Rogaland
Norway	Helse Nord/UNN	Tromsø	Troms
Norway	St. Olavs Hospital	Trondheim	Sør Trøndelag

Sponsors (4)

Lead Sponsor	Collaborator
Haukeland University Hospital	AstraZeneca, Helse Vest, Pfizer

Country where clinical trial is conducted

Norway, 

References & Publications (1)

Eikesdal HP, Yndestad S, Elzawahry A, Llop-Guevara A, Gilje B, Blix ES, Espelid H, Lundgren S, Geisler J, Vagstad G, Venizelos A, Minsaas L, Leirvaag B, Gudlaugsson EG, Vintermyr OK, Aase HS, Aas T, Balmaña J, Serra V, Janssen EAM, Knappskog S, Lønning PE — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Predictive and prognostic value of mutations in 300 cancer-related genes assessed in breast cancer tissue by next generation sequencing before starting neoadjuvant therapy.	Primary endpoint	Ten years
Secondary	To assess genetic/epigenetic changes within the tumor tissue during therapy	Secondary endpoint	Before vs. 16-24 wks after treatment start. Four years: summary of all patients treated.
Secondary	The objective response rate (ORR) of personalized medicine, compared to ORR for best standard-of-care using historical data for comparison	Secondary endpoint	Four years
Secondary	Tumor Ki67 reduction after 2 and 5 weeks of treatment in Arm A	Secondary endpoint	Assessment for each patient after 2 and 5 weeks of treatment. Four years - summary of all patients in arm A.
Secondary	To estimate recurrence-free and overall survival when patients are treated with the optimal personalized treatment available as of 2015, using historical data for comparison	Secondary endpoint	Ten years
Secondary	To evaluate the percentage of patients completing neoadjuvant treatment and completing surgery	Secondary endpoint	Four years
Secondary	Breast conserving surgery rate (potential to avoid mastectomy)	Secondary endpoint	Four years
Secondary	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Secondary endpoint	Ten years