Active — Not RecruitingPhase 2

To Assess Safety and Efficacy of Agents Targeting DNA Damage Repair With Olaparib Versus Olaparib Monotherapy.

United States273 participantsStarted 2018-03-07

Plain-language summary

This study is to assess the efficacy and safety of olaparib monotherapy versus olaparib in combination with an inhibitor of ATR (Ataxia-Telangiectasia Mutated (ATM) and Rad3-related protein kinase (Ceralasertib \[AZD6738\]) and olaparib monotherapy versus olaparib in combination with an inhibitor of WEE1 (adavosertib \[AZD1775\]) in second or third line setting in patients with Triple-negative breast cancer (TNBC) prospectively stratified by presence/absence of qualifying tumour mutation in genes involved in the homologous recombination repair (HRR) pathway. Treatment arms are olaparib monotherapy, olaparib+ Ceralasertib and olaparib+adavosertib. The study subject population will be divided into Stratum A, Stratum B, and Stratum C. Due to the different schedules of administration of each of the treatment options as well as their different toxicity profiles, the study is not blinded. Study has two stage consent process- stage 1 consent (molecular screening for HRR defects) and stage 2 consent (main study). Patients with TNBC and with known qualifying BRCAm, non BRCAm HRRm and non HRRm status will be offered the option of consenting to the main part of the study within the 28-day screening period. Following the ISRC meeting on 17 April 2019 a recommendation was made to close the adavosertib+olaparib treatment arm across all biomarker strata. Patients receiving treatment with adavosertib+olaparib treatment were offered the opportunity to continue treatment on olaparib monotherapy at the approved dose (300 mg bd). Following the closure of this arm the total number of patients randomised will be lower (approximately 350 patients). Approximately 300 patients will be randomised (using randomisation ratio 1:1) to 2 ongoing treatment arms plus an additional 47 patients to a 3rd arm (olaparib+adavosertib) prior to the arm being discontinued.

Who can participate

Age range18 Years – 130 Years

SexALL

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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion criteria

✓. Informed consent prior to any study specific procedures.
✓. Male or female ≥18 years of age.
✓. Progressive cancer at the time of study entry.
✓. Histologically or cytologically confirmed TNBC at initial diagnosis with evidence of metastatic disease and HER2 negative as per ASCO-CAP HER2 guideline recommendations 2013.
✓. Patients must have received at least 1 and no more than 2 prior lines of treatment for metastatic disease with an anthracycline (eg, doxorubicin, epirubicin) and/or a taxane (eg, paclitaxel, docetaxel) unless contraindicated, in either the neo-adjuvant, adjuvant or metastatic setting.
✓. Confirmed presence of qualifying HRR mutation or absence of any HRR mutation in tumour tissue by the Lynparza HRR assay.
✓. At least one measurable lesion that can be accurately assessed at baseline by computed tomography (CT) (magnetic resonance imaging \[MRI\] where CT is contraindicated) and is suitable for repeated assessment as per RECIST 1.1.
✓. Patients must have normal organ and bone marrow function measured within 28 days prior to randomization (defined in the protocol).

Exclusion criteria

What they're measuring

Progression-free Survival Per Stratum (BICR)

Timeframe: Until date of first documented progression or censoring date or date of death from any cause, whichever came first (assessed up to 32 months)

Progression-free Survival Per Stratum (Sensitivity Analysis)

Timeframe: Until date of first documented progression or censoring date or date of death from any cause, whichever came first (assessed up to 32 months)

Trial details

NCT IDNCT03330847

SponsorAstraZeneca

Sponsor typeINDUSTRY

Study typeINTERVENTIONAL

Primary completion2020-11-13

Results submitted2021-11-10

View on ClinicalTrials.gov More Metastatic Triple Negative Breast Cancer trials

Plain-language summary

Who can participate

Age range18 Years – 130 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion criteria

✓. Informed consent prior to any study specific procedures.
✓. Male or female ≥18 years of age.
✓. Progressive cancer at the time of study entry.
✓. Histologically or cytologically confirmed TNBC at initial diagnosis with evidence of metastatic disease and HER2 negative as per ASCO-CAP HER2 guideline recommendations 2013.
✓. Patients must have received at least 1 and no more than 2 prior lines of treatment for metastatic disease with an anthracycline (eg, doxorubicin, epirubicin) and/or a taxane (eg, paclitaxel, docetaxel) unless contraindicated, in either the neo-adjuvant, adjuvant or metastatic setting.
✓. Confirmed presence of qualifying HRR mutation or absence of any HRR mutation in tumour tissue by the Lynparza HRR assay.
✓. At least one measurable lesion that can be accurately assessed at baseline by computed tomography (CT) (magnetic resonance imaging \[MRI\] where CT is contraindicated) and is suitable for repeated assessment as per RECIST 1.1.
✓. Patients must have normal organ and bone marrow function measured within 28 days prior to randomization (defined in the protocol).

Exclusion criteria

What they're measuring

Progression-free Survival Per Stratum (BICR)

Timeframe: Until date of first documented progression or censoring date or date of death from any cause, whichever came first (assessed up to 32 months)

Progression-free Survival Per Stratum (Sensitivity Analysis)

Timeframe: Until date of first documented progression or censoring date or date of death from any cause, whichever came first (assessed up to 32 months)