Breast CancerPhase 2GeparOlaNCT02789332
Assessing the Efficacy of Paclitaxel and Olaparib in Comparison to Paclitaxel / Carboplatin Followed by Epirubicin/Cyclophosphamide as Neoadjuvant Chemotherapy in Patients With HER2-negative Early Breast Cancer and Homologous Recombination Deficiency
A Phase 2 study testing PwO, PwCb and EC in people with Breast Cancer and Triple Negative Breast Neoplasms, run by GBG Forschungs GmbH at 12 sites in Germany.
Trial summary
This is a multicenter, prospective, randomized, open-label phase II study evaluating the efficacy and safety of PO→EC as neoadjuvant treatment of operable and locally advanced breast cancer in patients with HR deficiency. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, Triple Negative Breast Neoplasms, HRpos Breast Neoplasms
- What is being tested?
- PwO, PwCb and EC
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 107 participants
- Where
- 12 sitesGermany
- Study dates
- Sep 2016to Feb 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent for all study specific procedures according to local regulatory requirements prior to beginning specific protocol procedures.
- Complete baseline documentation must be sent to GBG Forschungs GmbH.
- Unilateral or bilateral primary carcinoma of the breast, confirmed histologically by core biopsy. Fine-needle aspiration alone is not sufficient. Incisional biopsy is not allowed. In case of bilateral cancer, the investigator has to decide prospectively which side will be evaluated for the primary endpoint.
- Centrally confirmed negative HER2-status. Centrally confirmed estrogen and progesterone receptor, and Ki-67 status detected on core biopsy. ER/PR positive is defined as ≥1% stained cells and HER2-positive is defined as IHC 3+ or in-situ hybridisation (ISH) ratio ≥2.0. Formalin-fixed, paraffin-embedded (FFPE) breast tissue from core biopsy has therefore to be sent to the Dept. of Pathology at the Charité, Berlin prior to randomization.
- Centrally confirmed tumor Homologous Recombinant Deficiency score (tBRCA positive/mutated and/or HRD high). Patients with known gBRCA and/or tBRCA status can be enrolled prior to the central test results available.
- Tumor lesion in the breast with a palpable size of > 2 cm or a sonographical size of >1 cm in maximum diameter. If the tumor is not detectable with sonography mammography assessment can be considered. The lesion has to be measurable in two dimensions, preferably by sonography. In case of inflammatory disease, the extent of inflammation can be used as measurable lesion.
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- Patients must be in the following stages of disease:
- cT2 - cT4a-d or
- cT1c and cN+ or cT1c and pNSLN+ or
- cT1c and ER-neg and PR-neg or
- cT1c and Ki67>20% In patients with multifocal or multicentric breast cancer, the largest lesion should be measured and at least one lesion has to meet the above criteria
- Age > 18 years.
- Karnofsky Performance status index ≥ 80%.
- Normal cardiac function must be confirmed by ECG and cardiac ultrasound (LVEF or shortening fraction) within 3 months prior to randomization. Results must be above the normal limit of the institution.
- Laboratory requirements:
- Hematology
- Absolute neutrophil count (ANC) ≥2.0 x 109 / L and
- Platelets ≥100 x 109 / L and
- Hemoglobin ≥10 g/dL (≥ 6.2 mmol/L) Hepatic function
- Total bilirubin ≥1.5x UNL and
- ASAT (SGOT) and ALAT (SGPT) ≥1.5x UNL and
- Alkaline phosphatase ≥2.5x UNL.
- Negative pregnancy test (urine or serum) within 14 days prior to randomization for all women of childbearing potential.
- Complete staging work-up within 3 months prior to randomization. All patients must have bilateral mammography, breast ultrasound (≥21 days, and in no case exceed 6 weeks prior to randomization) (Note MRI/ CT scan may be used as an alternative imaging technique). In case of high risk according to guidelines: chest X-ray (PA and lateral) or as an alternative breast MRI/CT, abdominal ultrasound or CT scan or MRI, and bone scan in case of high risk for primary metastasis according to guidelines. In case of positive bone scan, bone X-ray or CT scan is mandatory. Other tests may be performed as clinically indicated.
- Male or female patients
- Patients must be available and compliant for central diagnostics, treatment and follow-up.
Who cannot join
- Prior chemotherapy for any malignancy within 5 years.
- Prior radiation therapy for breast cancer within 5 years.
- Pregnant or lactating patients. Patients of childbearing potential must implement adequate non-hormonal contraceptive measures (barrier methods, intrauterine contraceptive devices, sterilization) during study treatment.
- Inadequate general condition (not fit for anthracycline-taxane-targeted agents-based chemotherapy).
- Previous malignant disease without being disease-free for less than 5 years (except CIS of the cervix and non-melanomatous skin cancer).
- Known or suspected congestive heart failure (>NYHA I) and / or coronary heart disease, angina pectoris requiring antianginal medication, previous history of myocardial infarction, evidence of transmural infarction on ECG, uncontrolled or poorly controlled arterial hypertension (i.e. BP >140 / 90 mm Hg under treatment with two antihypertensive drugs), rhythm abnormalities requiring permanent treatment, clinically significant valvular heart disease.
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- History of significant neurological or psychiatric disorders including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent.
- Patients currently in an institution by order of jurisdictional or governmental grounds.
- Currently active infection.
- Definite contraindications for the use of corticosteroids.
- Known hypersensitivity reaction to one of the compounds or incorporated substances used in this protocol.
- Concurrent treatment with:
- chronic corticosteroids unless initiated > 6 months prior to study entry and at low dose (10 mg or less methylprednisolone or equivalent).
- sex hormones. Prior treatment must be stopped before study entry.
- other experimental drugs or any other anti-cancer therapy.
- Participation in another clinical trial with any investigational, not marketed drug within 30 days prior to study entry.
- Prior use of a PARP-Inhibitor
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
Germany12 sites
Praxisklinik
Berlin, 10367
Universitätsklinikum Erlangen
Erlangen, Bavaria, 91054
Kliniken Esslingen, Gynäkologie Onkologie
Esslingen am Neckar, Baden-Wurttemberg, 73730
SRH Wald-Klinikum Gera GmbH
Gera, Thuringia, 07548
Martin-Luther-Universität Halle Wittenberg
Halle, Saxony-Anhalt, 06120
Sana Klinikum Hameln-Pyrmont
Hamelin, Lower Saxony, 31785
Gemeinschaftspraxis
Hildesheim, Lower Saxony, 31134
Elisabeth Krankenhaus
Kassel, Hesse, 34117
Onkologisches Zentrum am Rotkreuzklinikum München
München, Bavaria, 80638
Klinikum Südstadt
Rostock, Mecklenburg-Vorpommern, 18059
Johanniter-Krankenhaus Genthin-Stendal
Stendal, Saxony-Anhalt, 39576
Marienhospital Witten
Witten, North Rhine-Westphalia, 58452
About this study
Official title: A Randomized Phase II Trial to Assess the Efficacy of Paclitaxel and Olaparib in Comparison to Paclitaxel / Carboplatin Followed by Epirubicin/Cyclophosphamide as Neoadjuvant Chemotherapy in Patients With HER2-negative Early Breast Cancer and Homologous Recombination Deficiency (HRD Patients With Deleterious BRCA1/2 Tumor or Germline Mutation and/or HRD Score High)
This is a multicenter, prospective, randomized, open-label phase II study evaluating the efficacy and safety of PO→EC as neoadjuvant treatment of operable and locally advanced breast cancer in patients with HR deficiency. Patients will be randomized to receive
- paclitaxel 80 mg/m² iv weekly in combination with olaparib tablets 100 mg (4X25mg) twice daily for 12 weeks (65 patients) or
- paclitaxel 80 mg/m² iv weekly in combination with carboplatin AUC 2 iv weekly for 12 weeks (37 patients) both followed by 4 cycles of epirubicin 90 mg/m² and cyclophosphamide 600 mg/m² (EC) either every 3 or every 2 weeks followed by surgery.
The control arm was chosen to allow direct comparison with one of the currently considered standard of care regimen.
Read the detailed description
The efficacy of olaparib in germline HRD score high with or without BRCA 1/2 mutation carriers with breast cancer is not well described
- The efficacy and safety of olaparib included in a standard of care regimen like paclitaxel weekly followed by epirubicin and cyclophosphamide (Pw-->EC) is unknown
- Carboplatin increased the pCR rate in patients with triple-negative breast cancer (TNBC) in two randomized phase II neoadjuvant studies when added to an anthracycline, cyclophosphamide and paclitaxel (GeparSixto, CALBG 40603). pCR rates were even higher in patients with germline BRCA 1 or 2 mutations (ypT0/is ypN0 65%) and with HRD score high (ypT0/is ypN0 63%).
- The TNT study showed a doubling in response rate for patients receiving carboplatin vs docetaxel in patients with germline BRCA 1 or 2 mutations.
- There is a high correlation between tumor and germline BRCA 1/2 mutations.
- Data from Geparsixto study showed that triple negative breast patients have an HR deficiency in about 70% (67% have a high HRD and 30% have a tBRCA mutation)
- About 5% of tBRCA patients have a low HRD score
- gBRCA2 patients are older when diagnosed and are more likely to have an HRpos tumor.
- The GeparOLA study aims to support the decision for a phase III study exploring the addition of olaparib to a Pw-->EC schedule by providing an estimate on the pCR rate in the targeted population but also by providing estimate comparison to paclitaxel and carboplatin followed by epirubicin and cyclophosphamide (PCb-->EC) as carboplatin is more and more considered a standard option of care in HR deficient patients (tBRCA 1/2 mutations and/or HRD score high).
- Conditions
- Breast Cancer, Triple Negative Breast Neoplasms, HRpos Breast Neoplasms, BRCA 1 /2 and / or HRD
- Being tested
- PwO, PwCb, EC, Surgery after neoadjuvant Therapy, Stratification
- Keywords
- carboplatin, olaparib, pCR, neoadjuvant, triple-negative, hormonreceptor-positive, BRCA1/2, HRD, homologous recominant deficient, breast cancer, genetic testing (somatic and germline mutations)
- Medical subject headings
- Breast Neoplasms, Triple Negative Breast Neoplasms, Kenny-Caffey syndrome, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PwODrug
Also called Paclitaxel Olaparib over 12 weeks
paclitaxel 80 mg/m² iv weekly in combination with olaparib tablets 100 mg twice daily for 12 weeks (PwO) (65 patients)
PwCbDrug
Also called Paclitaxel Carboplatin over 12 weeks, Control arm currently considered standard of care regimen
paclitaxel 80 mg/m² iv weekly in combination with carboplatin AUC 2 iv weekly for 12 weeks (PwCb) (37 patients)
ECDrug
Also called Epirubicin 90 mg/m² and Cyclophosphamide 600 mg/m² (EC) either every 3 or every 2 weeks
both Arms followed by 4 cycles of epirubicin 90 mg/m² and cyclophosphamide 600 mg/m² (EC) either every 3 or every 2 weeks followed by surgery.
Surgery after neoadjuvant TherapyProcedure or surgery
In both study arms, treatment will be given until surgery, disease progression, unacceptable toxicity, or withdrawal of consent of the patients.
StratificationOther
Also called Randomization will be performed using Pocock minimization method, stratified for the following criteria:
Hormone-receptor status (HR+ vs HR-) Age < 40 years vs >= 40 years
| Study group | Role | What they receive |
|---|---|---|
| Paclitaxel with Carboplatin (PwCb) | Active comparator | paclitaxel 80 mg/m² iv weekly in combination with carboplatin AUC 2 iv weekly for 12 weeks (37 patients) followed by 4 cycles of epirubicin 90 mg/m² and cyclophosphamide 600 mg/m² (EC) either every 3 or every 2 weeks followed by surgery. Receives: Drug: PwCb; Drug: EC; Procedure: Surgery after neoadjuvant Therapy; Other: Stratification |
| Paclitaxel with Olaparib (PwO) | Experimental | paclitaxel 80 mg/m² iv weekly in combination with olaparib tablets 100 mg twice daily for 12 weeks (65 patients)
followed by 4 cycles of epirubicin 90 mg/m² and cyclophosphamide 600 mg/m² (EC) either every 3 or every 2 weeks followed by surgery. Receives: Drug: PwO; Drug: EC; Procedure: Surgery after neoadjuvant Therapy; Other: Stratification |
What is being measured
The primary outcome is the main question the study is designed to answer.
response by pCR =ypT0/is ypN0
Assess the efficacy of olaparib in HER2-negative early Breast Cancer and HRD (BRCA 1/2 mutations and/or HRD positive). Pathological complete response of breast and lymph nodes (ypT0/is ypN0) defined as no microscopic evidence of residual invasive viable tumor cells in all resected specimens of the breast and axilla.
Pathological response will be assessed considering all removed breast and lymphatic tissues from all surgeries.
Measured: 24 weeks
Secondary outcomes (8)
response by pCR =ypT0/is ypN0
To assess the pCR rates of patients receiving PO→EC and the pCR rates of patients receiving paclitaxel and carboplatin followed by EC (PCb→EC)
Measured: 12 weeks
response by pCR =ypT0/is ypN0 in stratified subgroups
To assess the pCR rates (ypT0/is, ypN0) in the stratified subgroups
Measured: 24 weeks
response by pCR according to other definitions
To determine other pCR rates (ypT0 ypN0; ypT0 ypN0/+; ypT0/is ypN0/+; ypT(any) ypN0) of patients receiving PO→EC and to compare them with the pCR rates of patients receiving PCb→EC.
Measured: 24 weeks
response by pCR in HRD high versus tBRCA
To assess the pCR rate in HRD high with vs without tBRCA mutation
Measured: 24 weeks
Response rate by sono and/or mammo
To determine the response rates of the breast tumor and axillary nodes based on physical examination and imaging tests (sonography, mammography, or MRI) with PO→EC and to compare it with PCb→EC. Clinical (c) and imaging (i) response will be assessed after EC and before surgery by physical examination and imaging tests. Sonography is the preferred examination, however, if sonography appears not to provide valid results or is not performed, other imaging tests will be considered.
Measured: 12 weeks
Response rate by sono and/or mammo
To determine the response rates of the breast tumor and axillary nodes based on physical examination and imaging tests (sonography, mammography, or MRI) with PO→EC and to compare it with PCb→EC. Clinical (c) and imaging (i) response will be assessed after EC and before surgery by physical examination and imaging tests. Sonography is the preferred examination, however, if sonography appears not to provide valid results or is not performed, other imaging tests will be considered.
Measured: 24 weeks
Breast Conservation rate
To determine the breast conservation rate with PO→EC and to compare it with PCb→EC. Breast conservation is defined as tumorectomy, segmentectomy or quadrantectomy as a most radical surgery.
Measured: 24 weeks
Toxicity of treatment
To assess the toxicity and compliance of PO→EC and to compare it with PCb→EC. Tolerability and safety will be assessed on the basis of adverse events, serious adverse events, adverse events of special interest and treatment discontinuations. Safety by toxicity grades is defined by the NCI-CTCAE version 4.0.
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2016 (estimated)
- Study startSep 2016
- Primary completionFeb 2019
- Study completionFeb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 107 participants (actual)
Sponsor and investigators
- Lead sponsor
- GBG Forschungs GmbH
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor
- Investigators
- Sibylle 0 Loibl, Prof., MD, Study chair, Sibylle Loibl, Prof., MD ASCO, ESGO, ESMO, DKG, DGGG, AGO, DGS, BIG, BCIRG, St. Gallen Faculty Member, SABCS Faculty member
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02789332
- Sponsor's protocol ID
- GBG90
- Acronym
- GeparOla
- Status last verified
- Mar 2020
- First submitted
- 23 May 2016
- Last updated
- 17 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Von Minckwitz G, Timms K, Untch M, Elkin E P, Fasching P A, Schneeweiss A et al. Prediction of pathological complete response (pCR) by Homologous Recombination Deficiency (HRD) after carboplatin-containing neoadjuvant chemotherapy in patients with TNBC: Results from GeparSixto. J Clin Oncol 33, 2015 (suppl; abstr 1004)
Tutt A, Ellis P, Kilburn L et al. The TNT trial: A randomized phase III trial of carboplatin (C) compared with docetaxel (D) for patients with metastatic or recurrent locally advanced triple negative or BRCA1/2 breast cancer. SABCS 2014.
Sikov WM, Berry DA, Perou CM, Singh B, Cirrincione CT, Tolaney SM, Kuzma CS, Pluard TJ, Somlo G, Port ER, Golshan M, Bellon JR, Collyar D, Hahn OM, Carey LA, Hudis CA, Winer EP. Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once-per-week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603 (Alliance). J Clin Oncol. 2015 Jan 1;33(1):13-21. doi: 10.1200/JCO.2014.57.0572. Epub 2014 Aug 4.
PubMed 25092775von Minckwitz G, Schneeweiss A, Loibl S, Salat C, Denkert C, Rezai M, Blohmer JU, Jackisch C, Paepke S, Gerber B, Zahm DM, Kummel S, Eidtmann H, Klare P, Huober J, Costa S, Tesch H, Hanusch C, Hilfrich J, Khandan F, Fasching PA, Sinn BV, Engels K, Mehta K, Nekljudova V, Untch M. Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial. Lancet Oncol. 2014 Jun;15(7):747-56. doi: 10.1016/S1470-2045(14)70160-3. Epub 2014 Apr 30.
PubMed 24794243DOI: 10.1200/JCO.2019.37.15_suppl.506 Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019) 506-506. Fasching PA, Jackisch J, Rhiem K et al. GeparOLA: A randomized phase II trial to assess the efficacy of paclitaxel and olaparib in comparison to paclitaxel/carboplatin followed by epirubicin/cyclophosphamide as neoadjuvant chemotherapy in patients (pts) with HER2-negative early breast cancer (BC) and homologous recombination deficiency (HRD). J Clin Oncol 2019; 37.15_suppl.506; oral presentation
Fasching PA, Link T, Hauke J, Seither F, Jackisch C, Klare P, Schmatloch S, Hanusch C, Huober J, Stefek A, Seiler S, Schmitt WD, Uleer C, Doering G, Rhiem K, Schneeweiss A, Engels K, Denkert C, Schmutzler RK, Hahnen E, Untch M, Burchardi N, Blohmer JU, Loibl S; German Breast Group and Arbeitsgemeinschaft Gynakologische Onkologie Breast. Neoadjuvant paclitaxel/olaparib in comparison to paclitaxel/carboplatinum in patients with HER2-negative breast cancer and homologous recombination deficiency (GeparOLA study). Ann Oncol. 2021 Jan;32(1):49-57. doi: 10.1016/j.annonc.2020.10.471. Epub 2020 Oct 21.
PubMed 33098995
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase II Trial to Assess the Efficacy of Paclitaxel and Olaparib in Comparison to Paclitaxel / Carboplatin Followed by Epirubicin/Cyclophosphamide as Neoadjuvant Chemotherapy in Patients With HER2-negative Early Breast Cancer and Homologous Recombination Deficiency (HRD Patients With Deleterious BRCA1/2 Tumor or Germline Mutation and/or HRD Score High)
- ClinicalTrials.gov ID
- NCT02789332
- Acronym / sponsor ID
- GeparOla / GBG90
- Conditions
- Breast Cancer, Triple Negative Breast Neoplasms, HRpos Breast Neoplasms, BRCA 1 /2 and / or HRD
- Keywords
- carboplatin, olaparib, pCR, neoadjuvant, triple-negative, hormonreceptor-positive, BRCA1/2, HRD, homologous recominant deficient
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 107 participants (actual)
- Lead sponsor
- GBG Forschungs GmbHUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- Sep 2016 (actual)
- Primary completion
- Feb 2019 (actual)
- Study completion
- Feb 2020 (actual)
- First posted
- 3 Jun 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multicenter, prospective, randomized, open-label phase II study evaluating the efficacy and safety of PO→EC as neoadjuvant treatment of operable and locally advanced breast cancer in patients with HR deficiency. Patients will be randomized to receive
- paclitaxel 80 mg/m² iv weekly in combination with olaparib tablets 100 mg (4X25mg) twice daily for 12 weeks (65 patients) or
- paclitaxel 80 mg/m² iv weekly in combination with carboplatin AUC 2 iv weekly for 12 weeks (37 patients) both followed by 4 cycles of epirubicin 90 mg/m² and cyclophosphamide 600 mg/m² (EC) either every 3 or every 2 weeks followed by surgery.
The control arm was chosen to allow direct comparison with one of the currently considered standard of care regimen.
Detailed description
The efficacy of olaparib in germline HRD score high with or without BRCA 1/2 mutation carriers with breast cancer is not well described
- The efficacy and safety of olaparib included in a standard of care regimen like paclitaxel weekly followed by epirubicin and cyclophosphamide (Pw-->EC) is unknown
- Carboplatin increased the pCR rate in patients with triple-negative breast cancer (TNBC) in two randomized phase II neoadjuvant studies when added to an anthracycline, cyclophosphamide and paclitaxel (GeparSixto, CALBG 40603). pCR rates were even higher in patients with germline BRCA 1 or 2 mutations (ypT0/is ypN0 65%) and with HRD score high (ypT0/is ypN0 63%).
- The TNT study showed a doubling in response rate for patients receiving carboplatin vs docetaxel in patients with germline BRCA 1 or 2 mutations.
- There is a high correlation between tumor and germline BRCA 1/2 mutations.
- Data from Geparsixto study showed that triple negative breast patients have an HR deficiency in about 70% (67% have a high HRD and 30% have a tBRCA mutation)
- About 5% of tBRCA patients have a low HRD score
- gBRCA2 patients are older when diagnosed and are more likely to have an HRpos tumor.
- The GeparOLA study aims to support the decision for a phase III study exploring the addition of olaparib to a Pw-->EC schedule by providing an estimate on the pCR rate in the targeted population but also by providing estimate comparison to paclitaxel and carboplatin followed by epirubicin and cyclophosphamide (PCb-->EC) as carboplatin is more and more considered a standard option of care in HR deficient patients (tBRCA 1/2 mutations and/or HRD score high).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Paclitaxel with Carboplatin (PwCb) | Active comparator | Drug: PwCb, Drug: EC, Procedure: Surgery after neoadjuvant Therapy, Other: Stratificationpaclitaxel 80 mg/m² iv weekly in combination with carboplatin AUC 2 iv weekly for 12 weeks (37 patients) followed by 4 cycles of epirubicin 90 mg/m² and cyclophosphamide 600 mg/m² (EC) either every 3 or every 2 weeks followed by surgery. |
| Paclitaxel with Olaparib (PwO) | Experimental | Drug: PwO, Drug: EC, Procedure: Surgery after neoadjuvant Therapy, Other: Stratificationpaclitaxel 80 mg/m² iv weekly in combination with olaparib tablets 100 mg twice daily for 12 weeks (65 patients) followed by 4 cycles of epirubicin 90 mg/m² and cyclophosphamide 600 mg/m² (EC) either every 3 or every 2 weeks followed by surgery. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- Written informed consent for all study specific procedures according to local regulatory requirements prior to beginning specific protocol procedures.
- Complete baseline documentation must be sent to GBG Forschungs GmbH.
- Unilateral or bilateral primary carcinoma of the breast, confirmed histologically by core biopsy. Fine-needle aspiration alone is not sufficient. Incisional biopsy is not allowed. In case of bilateral cancer, the investigator has to decide prospectively which side will be evaluated for the primary endpoint.
- Centrally confirmed negative HER2-status. Centrally confirmed estrogen and progesterone receptor, and Ki-67 status detected on core biopsy. ER/PR positive is defined as ≥1% stained cells and HER2-positive is defined as IHC 3+ or in-situ hybridisation (ISH) ratio ≥2.0. Formalin-fixed, paraffin-embedded (FFPE) breast tissue from core biopsy has therefore to be sent to the Dept. of Pathology at the Charité, Berlin prior to randomization.
- Centrally confirmed tumor Homologous Recombinant Deficiency score (tBRCA positive/mutated and/or HRD high). Patients with known gBRCA and/or tBRCA status can be enrolled prior to the central test results available.
Key exclusion criteria (17 listed)
- Prior chemotherapy for any malignancy within 5 years.
- Prior radiation therapy for breast cancer within 5 years.
- Pregnant or lactating patients. Patients of childbearing potential must implement adequate non-hormonal contraceptive measures (barrier methods, intrauterine contraceptive devices, sterilization) during study treatment.
- Inadequate general condition (not fit for anthracycline-taxane-targeted agents-based chemotherapy).
- Previous malignant disease without being disease-free for less than 5 years (except CIS of the cervix and non-melanomatous skin cancer).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PwOAlso: Paclitaxel Olaparib over 12 weekspaclitaxel 80 mg/m² iv weekly in combination with olaparib tablets 100 mg twice daily for 12 weeks (PwO) (65 patients) | Drug | Paclitaxel with Olaparib (PwO) |
| PwCbAlso: Paclitaxel Carboplatin over 12 weeks, Control arm currently considered standard of care regimenpaclitaxel 80 mg/m² iv weekly in combination with carboplatin AUC 2 iv weekly for 12 weeks (PwCb) (37 patients) | Drug | Paclitaxel with Carboplatin (PwCb) |
| ECAlso: Epirubicin 90 mg/m² and Cyclophosphamide 600 mg/m² (EC) either every 3 or every 2 weeksboth Arms followed by 4 cycles of epirubicin 90 mg/m² and cyclophosphamide 600 mg/m² (EC) either every 3 or every 2 weeks followed by surgery. | Drug | Paclitaxel with Carboplatin (PwCb), Paclitaxel with Olaparib (PwO) |
| Surgery after neoadjuvant TherapyIn both study arms, treatment will be given until surgery, disease progression, unacceptable toxicity, or withdrawal of consent of the patients. | Procedure or surgery | Paclitaxel with Carboplatin (PwCb), Paclitaxel with Olaparib (PwO) |
| StratificationAlso: Randomization will be performed using Pocock minimization method, stratified for the following criteria:Hormone-receptor status (HR+ vs HR-) Age < 40 years vs >= 40 years | Other | Paclitaxel with Carboplatin (PwCb), Paclitaxel with Olaparib (PwO) |
Primary outcome
response by pCR =ypT0/is ypN0
Time frame: 24 weeks
Assess the efficacy of olaparib in HER2-negative early Breast Cancer and HRD (BRCA 1/2 mutations and/or HRD positive). Pathological complete response of breast and lymph nodes (ypT0/is ypN0) defined as no microscopic evidence of residual invasive viable tumor cells in all resected specimens of the breast and axilla. Pathological response will be assessed considering all removed breast and lymphatic tissues from all surgeries.
8 secondary outcomes
response by pCR =ypT0/is ypN0
Time frame: 12 weeks
response by pCR =ypT0/is ypN0 in stratified subgroups
Time frame: 24 weeks
response by pCR according to other definitions
Time frame: 24 weeks
response by pCR in HRD high versus tBRCA
Time frame: 24 weeks
Response rate by sono and/or mammo
Time frame: 12 weeks
Response rate by sono and/or mammo
Time frame: 24 weeks
Breast Conservation rate
Time frame: 24 weeks
Toxicity of treatment
Time frame: 24 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2020.
- BackgroundVon Minckwitz G, Timms K, Untch M, Elkin E P, Fasching P A, Schneeweiss A et al. Prediction of pathological complete response (pCR) by Homologous Recombination Deficiency (HRD) after carboplatin-containing neoadjuvant chemotherapy in patients with TNBC: Results from GeparSixto. J Clin Oncol 33, 2015 (suppl; abstr 1004)
- BackgroundTutt A, Ellis P, Kilburn L et al. The TNT trial: A randomized phase III trial of carboplatin (C) compared with docetaxel (D) for patients with metastatic or recurrent locally advanced triple negative or BRCA1/2 breast cancer. SABCS 2014.
- Background: PubMed 25092775Sikov WM, Berry DA, Perou CM, Singh B, Cirrincione CT, Tolaney SM, Kuzma CS, Pluard TJ, Somlo G, Port ER, Golshan M, Bellon JR, Collyar D, Hahn OM, Carey LA, Hudis CA, Winer EP. Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once-per-week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603 (Alliance). J Clin Oncol. 2015 Jan 1;33(1):13-21. doi: 10.1200/JCO.2014.57.0572. Epub 2014 Aug 4.
- Background: PubMed 24794243von Minckwitz G, Schneeweiss A, Loibl S, Salat C, Denkert C, Rezai M, Blohmer JU, Jackisch C, Paepke S, Gerber B, Zahm DM, Kummel S, Eidtmann H, Klare P, Huober J, Costa S, Tesch H, Hanusch C, Hilfrich J, Khandan F, Fasching PA, Sinn BV, Engels K, Mehta K, Nekljudova V, Untch M. Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial. Lancet Oncol. 2014 Jun;15(7):747-56. doi: 10.1016/S1470-2045(14)70160-3. Epub 2014 Apr 30.
- Results publicationDOI: 10.1200/JCO.2019.37.15_suppl.506 Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019) 506-506. Fasching PA, Jackisch J, Rhiem K et al. GeparOLA: A randomized phase II trial to assess the efficacy of paclitaxel and olaparib in comparison to paclitaxel/carboplatin followed by epirubicin/cyclophosphamide as neoadjuvant chemotherapy in patients (pts) with HER2-negative early breast cancer (BC) and homologous recombination deficiency (HRD). J Clin Oncol 2019; 37.15_suppl.506; oral presentation
- Derived from this study: PubMed 33098995Fasching PA, Link T, Hauke J, Seither F, Jackisch C, Klare P, Schmatloch S, Hanusch C, Huober J, Stefek A, Seiler S, Schmitt WD, Uleer C, Doering G, Rhiem K, Schneeweiss A, Engels K, Denkert C, Schmutzler RK, Hahnen E, Untch M, Burchardi N, Blohmer JU, Loibl S; German Breast Group and Arbeitsgemeinschaft Gynakologische Onkologie Breast. Neoadjuvant paclitaxel/olaparib in comparison to paclitaxel/carboplatinum in patients with HER2-negative breast cancer and homologous recombination deficiency (GeparOLA study). Ann Oncol. 2021 Jan;32(1):49-57. doi: 10.1016/j.annonc.2020.10.471. Epub 2020 Oct 21.
- GeparOla websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sibylle 0 Loibl, Prof., MD study chair
Sibylle Loibl, Prof., MD ASCO, ESGO, ESMO, DKG, DGGG, AGO, DGS, BIG, BCIRG, St. Gallen Faculty Member, SABCS Faculty member
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PwO, PwCb and EC in people with Breast Cancer and Triple Negative Breast Neoplasms, run by GBG Forschungs GmbH at 12 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 26 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
response by pCR =ypT0/is ypN0 (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02789332, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2020.