Temozolomide Monotherapy or in Combination With Olaparib in Patients With Triple Negative Breast Cancer (TNBC)

NCT05128734 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: TMZ-TNBC
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized phase II study to evaluate the disease control rate (DCR) of patients with metastatic or locally advanced METHYLATED 06-methylguanine-DNA methyltransferase (MGMT) with triple-negative breast cancer (TNBC) treated with Temozolomide ± Olaparib. Patients will be randomized 1:1 to Treatment Arm 1 (temozolomide treatment) or Arm 2 (temozolomide plus olaparib treatment).

Conditions

Breast Cancer Triple Negative

Keywords

METHYLATED 06-methylguanine-DNA methyltransferase (MGMT); Triple-Negative Breast Cancer; TNBC; Temozolomide; Olaparib

Outcome Measures

Primary Outcomes (1)

• Disease Control Rate (DCR)

  To determine DCR by assessing complete/partial response or stable disease, as per RECIST 1.1 in patients with mMGMT TNBC treated with Temozolomide ± Olaparib.

  From the date of first study drug dosing to the date of first documented complete response or partial response or stable disease, whichever came first, assessed up to 5 years.

Secondary Outcomes (4)

• Progression Free Survival (PFS)

  From the date of first study drug dosing to the date of first documented disease progression, assessed up to 5 years.

• Overall Survival (OS)

  From the date of first study drug dosing to the date of death, assessed up to 5 years.

• Number of adverse events in participants treated with Temozolomide ± Olaparib as assessed by CTCAE version 5.0.

  From the date of first study drug dosing until the last date of study drug dosing, assessed up to 5 years.

• Duration of Response (DoR)

  From the date of radiographic documentation of complete response or partial response or stable disease to the date of documented progression or death, whichever came first, up to 5 years.

Other Outcomes (5)

• Correlative Analyses

  Baseline

• Disease control rate in patients with BRCAness phenotype

  From the date of first study drug dosing to the date of first documented complete response or partial response or stable disease, whichever came first, assessed up to 5 years.

• Progression Free Survival in patients with BRCAness phenotype

  From the date of first study drug dosing to the date of first documented disease progression, assessed up to 5 years.

Study Arms (2)

Temozolomide Arm

EXPERIMENTAL

Temozolomide: 50 mg/m2 daily in cycles of 21 days

Drug: Temozolomide

Temozolomide+Olaparib Arm

EXPERIMENTAL

Temozolomide 75 mg/m2 day 1 to day 7 with Olaparib 200 mg BID, oral, day 1 to day 7 in cycles of 21 days

Drug: Temozolomide; Drug: Olaparib

Interventions

Temozolomide DRUG

Temozolomidewill be administered orally for 7 days (D) every 21 days until progression of the disease in both arms.

Also known as: ACH-TEMOZOLOMIDE

Temozolomide Arm; Temozolomide+Olaparib Arm

Olaparib DRUG

Olaparib will be administered orally twice daily in treatment arm 2.

Also known as: LYNPARZA

Temozolomide+Olaparib Arm

Eligibility Criteria

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

You may qualify if:

• Female or male patients with triple negative breast cancer confirmed by pathology of the primary tumour or metastatic biopsy sample. Estrogen receptor (ER) and progesterone receptor (PgR) must be ≤2 Allred score by Immunohistochemistry (IHC); human epidermal growth factor receptor 2 (HER2) 0 or 1+ by IHC, or 2+ with confirmed negativity by in situ hybridization (ISH) assay.
• Available Formalin-Fixed Paraffin-Embedded (FFPE) tumour tissue. If archival tissue is not available, the participant will have the option to provide a fresh tumour tissue specimen from a newly obtained biopsy. If archival and fresh tissue are not available, the participants will be excluded.
• MGMT promoter methylated by clinical assay.
• Prior exposure to anthracyclines and taxanes in adjuvant/neoadjuvant and/or metastatic setting.
• At least one line of chemotherapy in the context of metastatic disease.
• ECOG performance status 0 or 1 (Appendix A).
• Age ≥ 18 years old.
• Measurable disease (at least one 1x1 cm or greater lesion evaluable by CT scan and/or clinically; i.e., includes clinically evaluable skin metastases). Patients with only metastases to the bone are not eligible (See Section 10 Measurement of Effect for the evaluation of measurable disease).
• Adequate hematological, renal and hepatic function according to all of the following laboratory values (to be performed within 4 weeks prior to start of study treatment):
• Absolute neutrophil count \> 1.5 x109/L
• Platelets \> 100 x109/L
• Serum creatinine \< 1.5 times upper limit of laboratory normal
• Total serum bilirubin \< 1.5 times upper limit of laboratory normal
• AST or ALT ≤ 2.5 times upper limit of laboratory normal
• Alkaline phosphatase of ≤ 2.5 times upper limit of laboratory normal

You may not qualify if:

• Patients who have received chemotherapy within 4 weeks or radiotherapy to a non-target site within 2 weeks prior to entering the study or who have not recovered from adverse events from prior anti-cancer therapy (residual toxicities \> Grade 1) with the exception of alopecia.
• Patients who are receiving any other investigational agents within 3 weeks of signing the main informed consent form.
• Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≥ 5 years.
• Patients with psychiatric illness/social situations/substance abuse that would limit compliance with study requirements.
• Pregnant, breastfeeding women, and subjects unable and/or unwilling to use contraception methods.
• Patients with metastatic disease to bone only.
• Prior treatment with Temozolomide or Olaparib.
• Patients who are hypersensitive to any ingredients in the formulation of Olaparib, temozolomide or to dacarbazine (DTIC).
• Known BRCA1 or BRCA2 germline mutation(s).
• Patients with HIV, Hepatitis B, or Hepatitis C infection.

Sponsors & Collaborators

• AHS Cancer Control Alberta: lead

Study Sites (1)

Arthur J.E. Child Comprehensive Cancer Centre

Calgary, Alberta, T2N 5G2, Canada

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

Temozolomide; olaparib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Don Morris, MD, PhD

  Arthur J.E. Child Comprehensive Cancer Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michelle Kan

CONTACT

587-231-5495; michelle.kan@ahs.ca

Study Design

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

Study Record Dates

• First Submitted: October 27, 2021
• First Posted: November 22, 2021
• Study Start: April 1, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: December 15, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)