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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02624973
Recruitment Status : Active, not recruiting
First Posted : December 9, 2015
Last Update Posted : August 27, 2021
Sponsor:
Collaborators:
Helse Vest
Pfizer
AstraZeneca
Information provided by (Responsible Party):
Haukeland University Hospital

Study Description
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Brief 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.

Condition or disease Intervention/treatment 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 cyclophosphamide (after 10 weeks of 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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 200 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: PErsonalized TREatment of High-risk MAmmary Cancer - the PETREMAC Trial
Actual Study Start Date : April 15, 2016
Actual Primary Completion Date : June 1, 2020
Estimated Study Completion Date : June 2030

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arms and Interventions
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Arm Intervention/treatment
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 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
Experimental: H
Triple negative breast cancer TP53 mutated
 Drug: Neoadjuvant olaparib
Drug: 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


Outcome Measures
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Primary Outcome Measures :
  1. 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 :
  1. 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

  2. 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

  3. 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

  4. 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

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

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

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


Eligibility Criteria
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Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
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
  • 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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02624973


Locations
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Norway
Akershus University Hospital
Lørenskog, Akershus, Norway
Haukeland University Hospital
Bergen, Hordaland, Norway, 5021
Helse Fonna
Haugesund, Rogaland, Norway
Helse Stavanger
Stavanger, Rogaland, Norway
Helse Førde
Førde, Sogn Og Fjordande, Norway
St. Olavs Hospital
Trondheim, Sør Trøndelag, Norway
Helse Nord/UNN
Tromsø, Troms, Norway
Sponsors and Collaborators
Haukeland University Hospital
Helse Vest
Pfizer
AstraZeneca
Investigators
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Principal Investigator: Hans Petter Eikesdal, MD PhD Consultant oncologist
More Information
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Publications of Results:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Haukeland University Hospital
ClinicalTrials.gov Identifier: NCT02624973    
Other Study ID Numbers: 2015/8463
First Posted: December 9, 2015    Key Record Dates
Last Update Posted: August 27, 2021
Last Verified: August 2021
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:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Tamoxifen
Cyclophosphamide
Docetaxel
Trastuzumab
Letrozole
Epirubicin
Olaparib
Palbociclib
Pertuzumab
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
Antineoplastic Agents, Immunological
Aromatase Inhibitors
Steroid Synthesis Inhibitors