The p53 breast cancer trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Helse Bergen HF

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

12 Oct 2024 → ongoing

Decision date (initial)

2024-10-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

KG Jebsen Foundation

External identifiers

EU CT number

2024-515135-29-00

EudraCT number

2016-003459-31

ClinicalTrials.gov

NCT02965950

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

The primary objectives of this trial is to prospectively evaluate the objective response rate (ORR)* of dose dense cyclophosphamide in patients with TP53 mutated breast cancer or TP53 wt breast cancer.

Secondary objectives 1

1. The secondary objectives of this trial are; - Identify molecular markers of therapy response/resistance and survival outcome, beyond TP53 mutations. - Assess whether responses are recorded among patients harbouring TP53 mutations belonging to one of the following mutation subgroups: - So-called “Gain of Function” mutations - Mutations located in the DNA-binding domain of the p53 protein - Mutations with loss of heterozygosity (LOH) in concert - Mutations in other genes in the p53 pathway - Percentage of patients with T2 tumors or locally advanced breast cancer with pathological complete response (pCR). - Clinical benefit rate (CBR), in patients with metastatic breast cancer. - Recurrence-free and overall survival, compared to historical data. - Safety and tolerability of the study treatment.

Conditions and MedDRA coding

breast cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Primary (T2 tumors or Locally advanced breast cancers; LABC) in need of pre-surgical chemotherapy or metastatic breast cancer in need of chemotherapy.
2. Resistance to endocrine therapy: Either i) estrogen and progesterone negative tumor, or ii) harboring an estrogen and / or progesterone positive tumor where regular endocrine therapies have failed or where the treating physician finds endocrine therapy not indicated
3. Prior cancer therapy: Metastatic disease: First line treatment: No prior chemotherapy*. Prior endocrine therapy +/- CDK4/6 inhibitor or mTOR inhibitors is allowed if hormone receptor positive, HER2 negative disease. * Only for patients with TP53 mutated disease. Previous adjuvant chemotherapy, including alkylating agents (cyclophosphamide a.o.) DocuSign Envelope ID: 00482556-BD7E-48A0-B3D5-54A7D3046AD9 Study protocol: The p53 breast cancer trial, version 1.9 24 and/or platinum, is allowed if completed >12 months prior to inclusion in the trial. Late-stage disease (approved protocol): i) Prior exposure to and resistance to a taxane regimen**. ii) Prior exposure to and resistance to an anthracycline regimen*** - iii) Previous adjuvant chemotherapy, including alkylating agents (cyclophosphamide a.o.) and/or platinum, is allowed if completed >12 months prior to inclusion in the trial. Primary breast cancer (T2 tumors or LABC): i) Prior exposure to and lack of response to a taxane regimen**. ii) Prior exposure to and lack of response to an anthracycline regimen*** *** Mandatory only for patients with TP53 wt tumors. ** For HER2 positive breast cancer, previous taxane + anti-HER2 treatment is required. In metastatic breast cancer resistance to taxanes/anthracyclines is defined as progressive disease (PD). In primary breast tumors lack of response is defined as stable disease (SD) after 4 courses of chemotherapy or PD, or SD/PD after initial response, or further taxane/anthracyclines is not possible due to toxicity. Breast cancer relapsing within 12 months subsequent to adjuvant taxanes or anthracyclines is considered resistant and re-exposure is not required prior to inclusion in the trial. This relates also to patients who could not receive proper taxane or anthracycline therapy due to side effects or other medical reasons.
4. The primary tumor or at least one metastatic lesion must be available for biopsy collection at protocol inclusion. Notably; for patients with primary metastatic breast cancer, TP53 status should be determined in a metastatic deposit; tissue from the primary tumor may not substitute (this relates both to patients with synchronous and metachronous metastatic disease).
5. Patients must have clinically and/or radiographically documented measurable breast cancer according to RECIST.
6. WHO performance status 0-1
7. Known tumor ER, PGR and HER2 status in the current situation, i.e. archival and historic breast cancer tissue can not be used for patients with relapse of the disease. However, patients can be included regardless of hormone receptor and HER2 status; in case such information lacks at inclusion, it may be analysed on the biopsy retrospectively.
8. Age >18 years
9. Radiology studies for tumor measurements and ecco cor for cardiac function must be performed within 28 days of commencing treatment per protocol (MRI breast for primary breast cancer and CT thorax/abdomen/pelvis and/or MRI + bone scintigraphy/bone scan for metastatic disease).
10. Before patient registration, written informed consent must be given according to national and local regulations.
11. Blood test requirements: ▪ Neutrophils > 1.0 x 109/L ▪ Platelets > 75 x 109/L ▪ Bilirubin < 20 μmol/L. ▪ Serum creatinine < 1.5 x ULN

Exclusion criteria 11

1. Co-morbidity that, based on the assessment of the treating physician, may preclude the use of cyclophosphamide at actual doses.
2. Psychological, familial, sociological or geographical condition(s) potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
3. Pregnant or lactating patients
4. 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.
5. Active cystitis (to be treated upfront)
6. Active bacterial infections
7. Urinary obstruction
8. Known hypersensitivity towards cyclophosphamide or pegfilgrastim, their metabolites and other ingredients in the drug administration formulation.
9. Patient not able to give an informed consent or comply with study regulations as deemed by study investigator.
10. Patients with HER2 positive, metastatic breast cancer in the first line setting (Arm C).
11. Amendment 2021: Previous platinum or cyclophosphamide chemotherapy (incl. EC90) if completed less than 12 months prior to inclusion in the trial.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Objective response rate

Secondary endpoints 1

1. pCR, Clinical benefit rate, Recurrence-free survival, safety and tolerability

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Helse Bergen HF

Sponsor organisation

Helse Bergen HF

Address

Haukelandsveien 22

City

Bergen

Postcode

5021

Country

Norway

Scientific contact point

Organisation

Helse Bergen HF

Contact name

Hanne Elisabet Dillekås

Public contact point

Organisation

Helse Bergen HF

Contact name

Hanne Elisabet Dillekås

Locations

1 EU/EEA country · 4 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 4 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