Evaluation of the effectiveness of genome analysis as a therapeutic decision tool for patients with metastatic breast cancer.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Unicancer

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

7 Apr 2014 → ongoing

Decision date (initial)

2024-10-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Astra Zeneca Laboratories

External identifiers

EU CT number

2024-518002-41-00

EudraCT number

2013-001652-36

ClinicalTrials.gov

NCT02299999

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Others, Efficacy, Safety

To evaluate whether treatment with targeted agents guided by high throughput molecular analyses (CGH array, next generation sequencing) improves progression-free survival as compared to maintenance chemotherapy in patients with metastatic breast cancer in a pooled analysis of SAFIR02 Breast trial substudy 1 and a sample of patients from the SAFIR-PI3K trial.
For the primary objective of targeted substudy 1, a comparison of the treatment arms will be performed in the subpopulation patients defined as ESCAT I/II and in the overall population

Secondary objectives 6

1. To compare progression-free survival in patients treated with anti-PDL1 antibody (durvalumab) with those treated with maintenance therapy, in patients without actionable genomic alteration in the immune substudy 2 (primary objective of the immune substudy 2).
2. In a pooled analysis of SAFIR02 Breast trial substudy 1 and a sample of patients from the SAFIR-PI3K trial : -To compare overall survival -To evaluate overall response rates and change in tumor size -To evaluate safety
3. In the immune substudy 2 : -To compare overall survival -To evaluate overall response rates and change in tumor size -To evaluate safety
4. To explore the efficacy (response rate, change in tumor size, progression-free survival, overall survival) and safety of the individual targeted agents in substudy 1,
5. To perform a prospective pooled analysis of SAFIR02 Lung and SAFIR02 Breast studies
6. To correlate molecular characteristics in patients with the efficacy endpoints (response rate, progression-free and overall survival) in each substudy.

Conditions and MedDRA coding

Patients with metastatic breast cancer in 1st or 2nd line of chemotherapy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Women (or men) with histologically proven breast cancer
2. Metastatic relapse or progression or stage IV at diagnosis
3. No Her2 over-expression
4. Patients with metastases (or primary tumour when locally advanced disease or stage IV at diagnosis) that can be biopsied, except bone metastases. In the case a fresh biopsy collection is not achievable, patients able to provide a FFPE biopsy sample of a metastasis (or primary tumour when locally advanced disease or stage IV at diagnosis) or FFPE cytoblock will be considered as well. ctDNA, ideally collected before chemotherapy initiation, will be a tertiary option in the following situation : existing tissue (fresh or FFPE) is not eligible for the study (i.e. <30% tumor cells, or insufficient size) AND patients cannot undergo a new biopsy (e.g. inaccessible location, or bone disease as the sole site, or patient real safety concerns).
5. Patients who are eligible for a first line of chemotherapy in metastatic setting (left to the discretion of investigators), or who are currently treated with a first line of chemotherapy with a maximum of 2 cycles at the time of biopsy.
6. For patients with HR+ disease, history of relapse or progression occurred during endocrine therapy, whatever the setting, or occurred less than 12 months after the end of endocrine therapy in adjuvant context
7. For HR+ / HER2- patients, should have received palbociclib if they are in the indication
8. Age ≥ 18 years.
9. WHO Performance Status 0/1.
10. Presence of measurable target lesion or evaluable disease according to RECIST criteria v1.1
11. Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses
12. Patient with social insurance coverage

Exclusion criteria 22

1. Spinal cord compression and/or symptomatic or progressive brain metastases (unless asymptomatic or treated and stable without steroids during the last 30 days).
2. Patients with all target lesions in a previously irradiated region, except if clear progression has been observed prior to study in at least one of them.
3. Patient who received more than 1 line of chemotherapy in metastatic setting at the time of the biopsy.
4. Patients who already had a genomic profile (both CGH and NGS analysis) in which no SAFIR02 targetable alterations have been identified (except for patients coming from SAFIR-TOR study).
5. Inability to swallow.
6. Major problem with intestinal absorption.
7. Any of the following cardiac criteria: - Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG - Any factors increasing the risk of QTc prolongation or 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 old or any concomitant medication known to prolong the QT interval - Experience of any of the following procedures or conditions in the preceding 12 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, past or current uncontrolled angina pectoris (Canadian Cardiovascular Society grade II-IV despite medical therapy), congestive heart failure NYHA Grade ≥2, torsades de pointes, current uncontrolled hypertension (BP ≥150/95 mmHg despite medical therapy), cardiomyopathy.
8. Past medical history of interstitial lung disease, drug-induced interstitial disease, radiation pneumonitis which requires steroïd treatment or any evidence of clinically interstitial lung disease.
9. Previous or current malignancies of other histologies within the last 5 years, with the exception of in situ carcinoma of the cervix, and adequately treated basal cell or squamous cell carcinoma of the skin.
10. Evidence of severe or uncontrolled systemic disease (active bleeding diatheses, or active Hepatitis B, C and HIV) or any other serious active infection).
11. Previous history of myelodysplastic syndrome or acute myeloid leukaemia
12. Medical diagnosis of acne rosacea, severe psoriasis and severe atopic eczema.
13. Prior exposure to anthracyclines or mitoxantrone with cumulative exposure in excess of 360 mg/m² for doxorubicin, 720 mg/m² for epirubicin, or 72 mg/m² for mitoxantrone
14. Previous treatment with the same agent or in the same class as one of those used in the SAFIR02 trial (patients who received this previous targeted agent without the target prescreening are eligible but may not be eligible for randomisation in substudy 1 if the treatment allocated by the MTB is in the same class).
15. History of retinal degenerative disease, eye injury or corneal surgery in the previous 3 months, past history of central serous retinopathy or retinal vein occlusion, intraoccular pressure >21 mmHg, or uncontrolled glaucoma
16. Women who are pregnant.
17. History of heamorrhagic or thrombotic stroke, TIA or other CNS bleeds.
18. Renal disease including glomerulonephritis, nephritic syndrome, Fanconi syndrome, renal tubular acidosis
19. Previous history of myelodysplastic syndrome or acute myeloid leukaemia
20. Patients using drugs that are known potent inhibitors or potent inducers or substrates of cytochrome P450 are not eligible if those treatments cannot be substituted during the randomized phase of the study
21. Any condition which in the Investigator’s opinion makes it undesirable for the subject to participate in the trial or which would jeopardize compliance with the protocol including recent history (past 12 months) of drug abuse or alcohol abuse.
22. Individuals deprived of liberty or placed under the authority of a tutor.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-free survival (PFS) is defined as the time from randomization to the first documented progression of disease or death, whatever the cause. The tumor assessments are made by the investigators based on RECIST 1.1 criteria ([Eisenhauer 2009]). Patients still alive at the time of analysis without documented progression (including lost to follow-up) will be censored at the last known alive date.

Secondary endpoints 3

1. Overall Survival (OS) is defined as the time from randomization to death due to any cause. Patients still alive at the time of analysis (including lost to follow-up) will be censored at the last known alive date.
2. Objective response (i.e. complete or partial response) will be defined using RECIST V1.1 criteria. Changes in tumor size over time will also be analysed
3. Evaluation of safety will be done according to NCI CTCAE v4.03 criteria

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Unicancer

Sponsor organisation

Unicancer

Address

101 Rue De Tolbiac

City

Paris

Postcode

75013

Country

France

Scientific contact point

Organisation

Unicancer

Contact name

Nourredine AIT RAHMOUNE

Public contact point

Organisation

Unicancer

Contact name

Nourredine AIT RAHMOUNE

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications