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Trial record 1 of 1 for:    PETREMAC
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PErsonalized TREatment of High-risk MAmmary Cancer - the PETREMAC Trial (PETREMAC)

This study is currently recruiting participants.
See Contacts and Locations
Verified June 2017 by Haukeland University Hospital
Sponsor:
Collaborators:
Helse Vest
Pfizer
AstraZeneca
Information provided by (Responsible Party):
Haukeland University Hospital
ClinicalTrials.gov Identifier:
NCT02624973
First received: November 30, 2015
Last updated: June 23, 2017
Last verified: June 2017
  Purpose
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.

Condition Intervention Phase
Breast Cancer Drug: Neoadjuvant tamoxifen + goserelin (premenopausal women) Drug: Neoadjuvant letrozole (postmenopausal women) Drug: Neoadjuvant endocrine therapy + palbociclib (if lack of response to endocrine therapy alone) Drug: Neoadjuvant docetaxel + cyclophosphamide Drug: Neoadjuvant docetaxel Drug: Neoadjuvant docetaxel + trastuzumab + pertuzumab Drug: Neoadjuvant docetaxel + cyclophosphamide + trastuzumab + pertuzumab Drug: Neoadjuvant olaparib Drug: Neoadjuvant olaparib + carboplatin (if lack of response to olaparib alone) Procedure: Breast conserving surgery or mastectomy + SNB/axillary dissection Radiation: Postoperative radiotherapy breast/chest wall + regional lymph nodes Drug: Adjuvant trastuzumab Drug: Adjuvant letrozole (postmenopausal women) Drug: Adjuvant tamoxifen + goserelin (premenopausal women) Drug: Adjuvant palbociclib (if palbociclib given neoadjuvant) Drug: Adjuvant Epirubicin+ Cyclophosphamide Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Basic Science
Official Title: PErsonalized TREatment of High-risk MAmmary Cancer - the PETREMAC Trial

Resource links provided by NLM:


Further study details as provided by Haukeland University Hospital:

Primary Outcome Measures:
  • Predictive and prognostic value of mutations in 300 cancer-related genes assessed in breast cancer tissue by next generation sequencing before starting neoadjuvant therapy. [ Time Frame: Ten years ]
    Primary endpoint


Secondary Outcome Measures:
  • To assess genetic/epigenetic changes within the tumor tissue during therapy [ Time Frame: Before vs. 16-24 wks after treatment start. Four years: summary of all patients treated. ]
    Secondary endpoint

  • The objective response rate (ORR) of personalized medicine, compared to ORR for best standard-of-care using historical data for comparison [ Time Frame: Four years ]
    Secondary endpoint

  • Tumor Ki67 reduction after 2 and 5 weeks of treatment in Arm A [ Time Frame: Assessment for each patient after 2 and 5 weeks of treatment. Four years - summary of all patients in arm A. ]
    Secondary endpoint

  • 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 [ Time Frame: Ten years ]
    Secondary endpoint

  • To evaluate the percentage of patients completing neoadjuvant treatment and completing surgery [ Time Frame: Four years ]
    Secondary endpoint

  • Breast conserving surgery rate (potential to avoid mastectomy) [ Time Frame: Four years ]
    Secondary endpoint

  • Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: Ten years ]
    Secondary endpoint


Estimated Enrollment: 200
Study Start Date: April 2016
Estimated Study Completion Date: June 2030
Estimated Primary Completion Date: June 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
ER/PGR>50% TP53 wt
Drug: Neoadjuvant tamoxifen + goserelin (premenopausal women) Drug: Neoadjuvant letrozole (postmenopausal women) Drug: Neoadjuvant endocrine therapy + palbociclib (if lack of response to endocrine therapy 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 letrozole (postmenopausal women) Drug: Adjuvant tamoxifen + goserelin (premenopausal women) Drug: Adjuvant palbociclib (if palbociclib given neoadjuvant) Drug: Adjuvant Epirubicin+ Cyclophosphamide
Experimental: B
ER/PGR>50% TP53 mutated
Drug: Neoadjuvant docetaxel + cyclophosphamide 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 letrozole (postmenopausal women) Drug: Adjuvant tamoxifen + goserelin (premenopausal women)
Experimental: C
ER/PGR<50% TP53 wt
Drug: Neoadjuvant docetaxel 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 letrozole (postmenopausal women) Drug: Adjuvant tamoxifen + goserelin (premenopausal women)
Experimental: D
ER/PGR<50% TP53 mutated
Drug: Neoadjuvant docetaxel + cyclophosphamide 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 letrozole (postmenopausal women) Drug: Adjuvant tamoxifen + goserelin (premenopausal women)
Experimental: E
HER2+ TP53 wt
Drug: Neoadjuvant docetaxel + trastuzumab + pertuzumab 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 Drug: Adjuvant letrozole (postmenopausal women) Drug: Adjuvant tamoxifen + goserelin (premenopausal women)
Experimental: F
HER2+ TP53 mutated
Drug: Neoadjuvant docetaxel + cyclophosphamide + trastuzumab + pertuzumab 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 Drug: Adjuvant letrozole (postmenopausal women) Drug: Adjuvant tamoxifen + goserelin (premenopausal women)
Experimental: G
Triple negative breast cancer TP53 wt
Drug: Neoadjuvant olaparib Drug: Neoadjuvant olaparib + carboplatin (if lack of response to 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
Experimental: H
Triple negative breast cancer TP53 mutated
Drug: Neoadjuvant olaparib Drug: Neoadjuvant olaparib + carboplatin (if lack of response to 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

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02624973

Contacts
Contact: Hans Petter Eikesdal, MD PhD +4755972010
Contact: Per Eystein Lønning, MD PhD +4755972010

Locations
Norway
Akershus University Hospital Recruiting
Lørenskog, Akershus, Norway
Contact: Jürgen Geisler, MD PhD         
Principal Investigator: Jürgen Geisler, MD PhD         
Sub-Investigator: Randi Mathiesen, MD PhD         
Haukeland University Hospital Recruiting
Bergen, Hordaland, Norway, 5021
Contact: Hans Petter Eikesdal, MD PhD    +4755972010      
Contact: Per Eystein Lønning, MD PhD    +4755972010      
Sub-Investigator: Vidhi Shukla, MD         
Principal Investigator: Hans Petter Eikesdal, MD PhD         
Sub-Investigator: Stian Knappskog, PhD         
Sub-Investigator: Turid Aas, MD PhD         
Sub-Investigator: Hildegunn Aase, MD         
Sub-Investigator: Åse Haug, MD         
Sub-Investigator: Oddbjørn Straume, MD PhD         
Sub-Investigator: Sindre Molvær, MD         
Helse Fonna Recruiting
Haugesund, Rogaland, Norway
Contact: Helge Espelid, MD         
Principal Investigator: Helge Espelid, MD         
Helse Stavanger Recruiting
Stavanger, Rogaland, Norway
Contact: Bjørnar Gilje, MD PhD         
Principal Investigator: Bjørnar Gilje, MD PhD         
Sub-Investigator: Emil Janssen, MD PhD         
Sub-Investigator: Ingvil Mjaaland, MD PhD         
Sub-Investigator: Oddmund Nordgård, PhD         
Helse Førde Recruiting
Førde, Sogn og Fjordande, Norway
Contact: Geirfinn Vagstad, MD         
Contact: Liv Jorunn Vassbotn, MD         
Principal Investigator: Geirfinn Vagstad, MD         
Sub-Investigator: Liv Jorunn Vassbotn, MD         
St. Olavs Hospital Recruiting
Trondheim, Sør Trøndelag, Norway
Contact: Steinar Lundgren, MD PhD         
Sub-Investigator: Tone Bathen, PhD         
Principal Investigator: Steinar Lundgren, MD PhD         
Helse Nord/UNN Recruiting
Tromsø, Troms, Norway
Contact: Egil S Blix, MD PhD         
Principal Investigator: Egil S Blix, MD PhD         
Sponsors and Collaborators
Haukeland University Hospital
Helse Vest
Pfizer
AstraZeneca
Investigators
Principal Investigator: Hans Petter Eikesdal, MD PhD Consultant oncologist
  More Information

Responsible Party: Haukeland University Hospital
ClinicalTrials.gov Identifier: NCT02624973     History of Changes
Other Study ID Numbers: 2015/8463
Study First Received: November 30, 2015
Last Updated: June 23, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Tumor genomic data will be made available after publication.

Keywords provided by Haukeland University Hospital:
neoadjuvant treatment
personalized medicine

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cyclophosphamide
Docetaxel
Letrozole
Olaparib
Palbociclib
Pertuzumab
Carboplatin
Trastuzumab
Tamoxifen
Epirubicin
Goserelin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Aromatase Inhibitors
Steroid Synthesis Inhibitors

ClinicalTrials.gov processed this record on July 27, 2017