The p53 Breast Cancer Trial

NCT02965950 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: 2016/8162016-003459-31
• Study Type: interventional
• Target: 190
• Locations: 1 country
• Sites: 5

Brief Summary

This is a multicenter, open labeled, phase 2 clinical trial, where patients are stratified to one of two treatment groups based on upfront TP53 mutation status; i.e. TP53 mutated vs. TP53 wt disease, and treated with dose-dense cyclphosphamide. Furthermore, patients included are stratified based on tumor stage; i.e. locally advanced breast cancer (M0 disease) or metastatic breast cancer (M1 disease). All participating cancer centers will prospectively include patients with breast cancer fulfilling the inclusion criteria. If patients do not respond to the experimental treatment as outlined in the protocol, treatment with dose-dense cyclophosphamide will be terminated, and further cancer treatment will continue at the treating oncologist's discretion. The response data for all patients who have received at least one chemotherapy course will be included in the final efficacy analysis. Tumor tissue, blood samples and radiology data will be collected before therapy starts, if therapy needs to be changed, and for patients with locally advanced breast cancer: at surgery. Response data will be evaluated closely during treatment, with clinical assessment of tumor size every two weeks for patients with locally advanced breast cancer and by radiology every eight weeks for patients with metastatic breast cancer. Evaluation of side effects/tolerance will be performed at every clinical visit, i.e. every two weeks for all patients included in the p53 trial.

Conditions

Locally Advanced Breast Cancer; Metastatic Breast Carcinoma

Keywords

breast cancer; TP53; cyclophosphamide

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR) measured clinically (with calipers) or radiologically per RECIST guidelines.

  ORR of dose dense cyclophosphamide in patients with TP53 mutated breast cancer or TP53 wt breast cancer.

  Four years

Secondary Outcomes (6)

• Number of patients harboring the same molecular aberration or set of aberrations, and which are associated with either response to treatment or survival.

  Four years

• Number of patients harboring the same TP53 mutation subtype

  Four years

• Number of patients achieving pathological complete response (pCR)

  Four years

• Recurrence-free survival

  14 years

• Overall survival

  14 years

Study Arms (5)

TP53 mutated, LABC

EXPERIMENTAL

Patients with locally advanced breast cancer, TP53 mutated disease. Dose-dense cyclophosphamide, after taxanes +/- anthracyclines.

Drug: Cyclophosphamide

TP53 mutated, MBC, first line

EXPERIMENTAL

Patients with metastatic breast cancer, TP53 mutated disease. Dose-dense cyclophosphamide first line metastatic disease

Drug: Cyclophosphamide

TP53 wt, LABC

EXPERIMENTAL

Patients with locally advanced breast cancer, TP53 wt disease. Dose-dense cyclophosphamide, after taxanes and anthracyclines.

Drug: Cyclophosphamide

TP53 wt, MBC

EXPERIMENTAL

Patients with metastatic breast cancer, TP53 wt disease. Dose-dense cyclophosphamide, after taxanes and anthracyclines.

Drug: Cyclophosphamide

TP53 mutated, MBC

EXPERIMENTAL

Patients with metastatic breast cancer, TP53 mutated disease. Dose-dense cyclophosphamide, after taxanes +/- anthracyclines.

Drug: Cyclophosphamide

Interventions

Cyclophosphamide DRUG

I.v. infusion

Also known as: ATC-number: L01A A01

TP53 mutated, LABC; TP53 mutated, MBC; TP53 mutated, MBC, first line; TP53 wt, LABC; TP53 wt, MBC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Locally advanced breast cancers in need of pre-surgical chemotherapy or metastatic breast cancer in need of chemotherapy.
• 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.
• \- Prior cancer therapy:
• Metastatic disease:
• First line treatment (amendment 2018):
• No prior chemotherapy\*. Prior endocrine therapy +/- CDK4/6 inhibitor or mTOR inhibitors is allowed if hormone receptor positive, HER2 negative disease.
• 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\*\* -mandatory only for patients with TP53 wt tumors.
• LABC:
• i) Prior exposure to and lack of response to to a taxane regimen\*\*. ii) Prior exposure to and lack of response to an anthracycline regimen\*\* - mandatory only for patients with TP53 wt tumors.
• Patients must have clinically and/or radiographically documented measurable breast cancer according to RECIST.
• WHO performance status 0-1
• Age \>18 years
• Radiology studies (CT thorax/abdomen and bone scintigraphy/bone scan) and ecco cor must be performed within 28 days prior to start of treatment.

You may not qualify if:

• Co-morbidity that, based on the assessment of the treating physician, may preclude the use of cyclophosphamide at actual doses.
• 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
• Pregnant or lactating patients.
• Active cystitis (to be treated upfront)
• Active bacterial infections
• Urinary obstruction
• Known hypersensitivity towards cyclophosphamide or pegfilgrastim, their metabolites and other ingredients in the drug administration formulation.
• Patient not able to give an informed consent or comply with study regulations as deemed by study investigator.
• Amendment 2018: Patients with HER2 positive, metastatic breast cancer in the first line setting (Arm C).

Sponsors & Collaborators

• Haukeland University Hospital: lead

Study Sites (5)

Haukeland University Hospital

Bergen, Hordaland, 5021, Norway

Location

St. Olavs Hospital

Trondheim, Sør Trøndelag, Norway

Location

Akershus University Hospital

Lørenskog, Norway

Location

Stavanger University Hospital

Stavanger, Norway

Location

University Hospital of Northern Norway

Tromsø, Norway

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Hans Petter Eikesdal, MD PhD

  Haukeland University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2016
• First Posted: November 17, 2016
• Study Start: October 1, 2016
• Primary Completion: May 1, 2024
• Study Completion (Estimated): May 1, 2033
• Last Updated: January 12, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will share

Locations

NO (5)