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

ConditionBreast Cancer Triple Negative
Trial statusNot yet recruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorAHS Cancer Control Alberta

About this trial

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).

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Temozolomide

    Drug

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

  • Olaparib

    Drug

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

Treatment groups

40 Participants
are divided into 2 treatment groups
Group A: Temozolomide ArmExperimental treatment 1 intervention
Group B: Temozolomide+Olaparib ArmExperimental treatment 2 interventions

Trial outcomes

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.

Time frame
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

1

Progression Free Survival (PFS)

To determine progression-free survival (PFS) of patients with mMGMT TNBC treated with Temozolomide ± Olaparib.

Time frame
From the date of first study drug dosing to the date of first documented disease progression, assessed up to 5 years.
2

Overall Survival (OS)

To determine OS by measuring the time interval from the date of the first dose of the study treatment until death due to any cause. Subjects who are still alive will be censored on the date of last contact.

Time frame
From the date of first study drug dosing to the date of death, assessed up to 5 years.
3

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

To determine the number of adverse events related to Temozolomide ± Olaparib treatment according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0, effective November 27, 2017 \[Common Terminology Criteria for Adverse Events (CTCAE).

Time frame
From the date of first study drug dosing until the last date of study drug dosing, assessed up to 5 years.
4

Duration of Response (DoR)

To determine the time duration between the radiographic documentation of complete response or partial response or stable disease (whichever is recorded first) until the first date that the progressive disease is documented or death.

Time frame
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

1

Correlative Analyses

Evaluation of promoter methylation and immunohistochemistry (IHC) targets relevant to MGMT and PARP repair pathways to identify patients most likely to derive benefit from temozolomide ± Olaparib.

Time frame
Baseline
2

Disease control rate in patients with BRCAness phenotype

To determine whether tumor BRCAness phenotype is associated with disease control rate in patients with mMGMT TNBC treated with temozolomide ± olaparib.

Time frame
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.
3

Progression Free Survival in patients with BRCAness phenotype

To determine whether tumor BRCAness phenotype is associated with progression-free survival in patients with mMGMT TNBC treated with temozolomide ± olaparib.

Time frame
From the date of first study drug dosing to the date of first documented disease progression, assessed up to 5 years.
4

Overall Survival in patients with BRCAness phenotype

To investigate whether tumour BRCAness phenotype is associated with overall survival in patients with mMGMT TNBC treated with temozolomide ± olaparib.

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

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

AHS Cancer Control Alberta

Lead sponsor

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: