Triple Negative Breast CancerPhase 2NCT02685657
Neoadjuvant Chemotherapy Docetaxel With or Without SELUMETINIB in Patients With Triple Negative Breast Cancer
A Phase 2 study testing Drug: Selumetinib, Doxorubicin and Cyclophosphamide in people with Triple Negative Breast Cancer, run by Russian Academy of Medical Sciences.
Trial summary
The purpose of this study is to increase survival of patients with early and locally advanced triple-negative breast cancer adding selumatinib to standard preoperative chemotherapy regimen. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Triple Negative Breast Cancer
- What is being tested?
- Drug: Selumetinib, Doxorubicin and Cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 164 participants
- Where
- No sites listed yet
- Study dates
- Sep 2016to Jan 2018
- 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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- • Written informed consent;
- Women with early and locally advanced breast cancer ( Stage IIB-IIIB: T2N1-2, T3-4/N0-2 or any T/N2)
- Triple negative breast cancer (absence of estrogen receptor (0-2 points), progesterone receptor (0-2 points), and HER2/neu receptor (IHC 0-1+ or IHC 2+ in the absence of her2/neu gene amplification as evidenced by FISH);
- Age: over 18 years;
- Eastern Cooperative Oncology Group (ECOG) score: 0-1 points;
- Left ventricular ejection fraction (LVEF) based on Echocardiogram (ECHO) or Multigated radionuclide angiography (MUGA scan): >55%
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- Laboratory values before the study start must meet the following criteria:
- Absolute neutrophil count > 1500/microlitre Platelet count > 100000/microlitre Hemoglobin level > 9.0 g/dl Albumin > 2,5 g/dl Normal plasma creatinine level or estimated glomerular filtration rate (eGFR) >60 ml/minute Total bilirubin level < 1.25 upper limit of normal (ULN) Aspartate aminotransferase (AST), alanine aminotransferase (ALT) < 3 x ULN;
- Patient is able to abide by the protocol requirements (in the opinion of the Investigator)
- Patient's and her sexual partner's willing to use reliable methods of contraception (condoms with spermicidal foams/gels, intrauterine device) during the study and for at least 4 weeks after discontinuation of study treatment.
- Negative serum pregnancy test for women with childbearing potential or evidence of a post-menopausal status (total cessation of menses for more than 1 year. The following age-specific requirements must also apply:
- Women < 60 years old: they would be considered post-menopausal if they have been amenorrheic for the past 12 months or more. The levels of Follicle-Stimulating Hormone (FSH) and estradiol must also be in the post-menopausal range (as per the institution).
- Women ≥ 60 years;
- Bilateral oophorectomy.
Who cannot join
- • Prior treatment (chemo-, hormone, radiation or immunotherapy) of breast cancer
- Major surgery within 28 days prior to enrollment;
- Known hypersensitivity to Docetaxel, SELUMETINIB or to the components of the investigational product;
- Cardiac conditions as follows:
- Uncontrolled hypertension (BP ≥ 150/95 mmHg despite medical therapy) b. Acute coronary syndrome within 6 months prior to starting treatment c. Uncontrolled Angina - Canadian Cardiovascular Society grade II-IV despite medical therapy (Appendix 3) d. Symptomatic heart failure New York Heart Association (NYHA) Class II-IV, prior or current cardiomyopathy (Appendix 4) e. Prior or current cardiomyopathy including but not limited to the following: i. Known hypertrophic cardiomyopathy ii. Known arrhythmogenic right ventricular cardiomyopathy iii. Previous moderate or severe impairment of left ventricular systolic function (Left ventricular ejection fraction (LVEF) <45% on echocardiography or equivalent on MuGA) even if full recovery has occurred.
- Severe valvular heart disease g. Baseline Left ventricular ejection fraction (LVEF) below the lower limit of normal (LLN) or <55% measured by echocardiography or institution's LLN for MUGA h. Atrial fibrillation with a ventricular rate >100 bpm on ECG at rest i. QTcF >450ms or other factors that increase the risk of QT prolongation
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- Pregnancy or lactation;
- Conditions (dementia, psychiatric or neurological disorders, drug addiction, alcoholism etc.) that limit patient's ability to undergo study procedures;
- Simultaneous participation in other clinical studies;
- Presence of acute or active chronic infections or other conditions (e.g. unstable or uncompensated respiratory, cardiac, hepatic, or renal disease, active bleeding diatheses or renal transplant), that in investigator's opinion may interfere with the treatment described in the study protocol;
- Have refractory nausea and vomiting, chronic gastrointestinal diseases (e.g., inflammatory bowel disease), or significant bowel resection that would adversely affect the absorption / bioavailability of the orally administered study medication
- History of another neoplasm (with the exception of adequately treated basal cell or cervical cancer in situ and cases when a cancer has been in remission for 5 years of more)
- Ophthalmological conditions as follows:
- Intra-ocular pressure >21 mmHg, or uncontrolled glaucoma (irrespective of intra-ocular pressure)
- Current or past history of retinal pigment epithelial detachment / central serous retinopathy
- Current or past history of retinal vein occlusion
Trial locations and contacts
No sites are listed yet.
About this study
Official title: A Phase II Randomized Multicenter Open Label Prospective Study of Neoadjuvant Chemotherapy Docetaxel With or Without MEK Inhibitor SELUMETINIB in Patients With Early and Locally Advanced Triple Negative Breast Cancer
The purpose of this study is to increase survival of patients with early and locally advanced triple-negative breast cancer adding selumatinib to standard preoperative chemotherapy regimen.
Read the detailed description
Molecular analysis of residual tumor after administration of neoadjuvant chemotherapy revealed several mechanisms of resistance to treatment. High frequency of RAS-RAF-MEK-ERK signal pathway activation was found in cells of triple negative breast cancer after neoadjuvant chemotherapy, which correlated with high proliferation index and low pathological complete response rate. Thus, inhibition of MEK molecule - an intermediary transducer of this pathway may decrease activity of this pathway and restore tumor sensitivity to cytostatic agents.
Hence, the use of SELUMETINIB, an oral selective inhibitor of MEK1/MEK2 kinases, in combination with Docetaxel should increase pathological complete response rate and in turn increase survival of patients with early and locally advanced triple-negative breast cancer.
- Conditions
- Triple Negative Breast Cancer
- Being tested
- Drug: Selumetinib, Doxorubicin, Cyclophosphamide, Docetaxel
- Medical subject headings
- Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Drug: SelumetinibDrug
Also called AZD6244
DoxorubicinDrug
CyclophosphamideDrug
DocetaxelDrug
| Study group | Role | What they receive |
|---|---|---|
| AC followed by Docetaxel with Selumetinib | Experimental | Doxorubicin 60 mg/m2 and Cyclophosphamide 600 mg/m2 as a single IV infusion on day 1 of every 3 week cycle then 75 mg/m2 of Docetaxel given as a single IV infusion on day 1 of every 3 week cycle, 75 mg of SELUMETINIB twice a day PO on days 1-21 of every 3 week cycle Receives: Drug: Drug: Selumetinib; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Docetaxel |
| AC followed by Docetaxel | Active comparator | Doxorubicin 60 mg/m2 and Cyclophosphamide 600 mg/m2 as a single IV infusion on day 1 of every 3 week cycle then 75 mg/m2 of Docetaxel given as a single IV infusion on day 1 of every 3 week cycle Receives: Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Docetaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
• Pathological complete response rate
Measured: After 24 weeks of neoadjuvant chemotherapy and surgery
Secondary outcomes (2)
• Overall clinical response rate
Measured: After 24 weeks of neoadjuvant chemotherapy
• Adverse events rate in both treatment groups
Measured: After 24 weeks of neoadjuvant chemotherapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2016 (estimated)
- Study startSep 2016
- Primary completionJan 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Triple Negative 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
- 164 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Russian Academy of Medical Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- Russian Society of Clinical Oncology
- Responsible party
- Principal investigator, Mona Frolova, Russian Academy of Medical Sciences
- Investigators
- Mona Frolova, Principal investigator, Russian Cancer Research Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02685657
- Sponsor's protocol ID
- ESR-14-10735
- Status last verified
- Feb 2016
- First submitted
- 13 Feb 2016
- Last updated
- 22 Feb 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Randomized Multicenter Open Label Prospective Study of Neoadjuvant Chemotherapy Docetaxel With or Without MEK Inhibitor SELUMETINIB in Patients With Early and Locally Advanced Triple Negative Breast Cancer
- ClinicalTrials.gov ID
- NCT02685657
- Acronym / sponsor ID
- ESR-14-10735
- Conditions
- Triple Negative Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 164 participants (estimated)
- Lead sponsor
- Russian Academy of Medical SciencesUniversity, hospital or other
- Collaborators
- Russian Society of Clinical Oncology
- Study start
- Sep 2016
- Primary completion
- Jan 2018 (estimated)
- First posted
- 19 Feb 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.
The purpose of this study is to increase survival of patients with early and locally advanced triple-negative breast cancer adding selumatinib to standard preoperative chemotherapy regimen.
Detailed description
Molecular analysis of residual tumor after administration of neoadjuvant chemotherapy revealed several mechanisms of resistance to treatment. High frequency of RAS-RAF-MEK-ERK signal pathway activation was found in cells of triple negative breast cancer after neoadjuvant chemotherapy, which correlated with high proliferation index and low pathological complete response rate. Thus, inhibition of MEK molecule - an intermediary transducer of this pathway may decrease activity of this pathway and restore tumor sensitivity to cytostatic agents.
Hence, the use of SELUMETINIB, an oral selective inhibitor of MEK1/MEK2 kinases, in combination with Docetaxel should increase pathological complete response rate and in turn increase survival of patients with early and locally advanced triple-negative breast cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AC followed by Docetaxel with Selumetinib | Experimental | Drug: Drug: Selumetinib, Drug: Doxorubicin, Drug: Cyclophosphamide, Drug: DocetaxelDoxorubicin 60 mg/m2 and Cyclophosphamide 600 mg/m2 as a single IV infusion on day 1 of every 3 week cycle then 75 mg/m2 of Docetaxel given as a single IV infusion on day 1 of every 3 week cycle, 75 mg of SELUMETINIB twice a day PO on days 1-21 of every 3 week cycle |
| AC followed by Docetaxel | Active comparator | Drug: Doxorubicin, Drug: Cyclophosphamide, Drug: DocetaxelDoxorubicin 60 mg/m2 and Cyclophosphamide 600 mg/m2 as a single IV infusion on day 1 of every 3 week cycle then 75 mg/m2 of Docetaxel given as a single IV infusion on day 1 of every 3 week cycle |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- • Written informed consent;
- Absolute neutrophil count > 1500/microlitre Platelet count > 100000/microlitre Hemoglobin level > 9.0 g/dl Albumin > 2,5 g/dl Normal plasma creatinine level or estimated glomerular filtration rate (eGFR) >60 ml/minute Total bilirubin level < 1.25 upper limit of normal (ULN) Aspartate aminotransferase (AST), alanine aminotransferase (ALT) < 3 x ULN;
- Patient is able to abide by the protocol requirements (in the opinion of the Investigator)
- Patient's and her sexual partner's willing to use reliable methods of contraception (condoms with spermicidal foams/gels, intrauterine device) during the study and for at least 4 weeks after discontinuation of study treatment.
- Negative serum pregnancy test for women with childbearing potential or evidence of a post-menopausal status (total cessation of menses for more than 1 year. The following age-specific requirements must also apply:
Key exclusion criteria (16 listed)
- • Prior treatment (chemo-, hormone, radiation or immunotherapy) of breast cancer
- Intra-ocular pressure >21 mmHg, or uncontrolled glaucoma (irrespective of intra-ocular pressure)
- Current or past history of retinal pigment epithelial detachment / central serous retinopathy
- Current or past history of retinal vein occlusion
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 |
|---|---|---|
| Drug: SelumetinibAlso: AZD6244 | Drug | AC followed by Docetaxel with Selumetinib |
| Doxorubicin | Drug | AC followed by Docetaxel, AC followed by Docetaxel with Selumetinib |
| Cyclophosphamide | Drug | AC followed by Docetaxel, AC followed by Docetaxel with Selumetinib |
| Docetaxel | Drug | AC followed by Docetaxel, AC followed by Docetaxel with Selumetinib |
Primary outcome
• Pathological complete response rate
Time frame: After 24 weeks of neoadjuvant chemotherapy and surgery
2 secondary outcomes
• Overall clinical response rate
Time frame: After 24 weeks of neoadjuvant chemotherapy
• Adverse events rate in both treatment groups
Time frame: After 24 weeks of neoadjuvant chemotherapy
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Feb 2016.
- Individual participant dataSharing planned: No
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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.
Mona Frolova principal investigator
Russian Cancer Research Center
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Drug: Selumetinib, Doxorubicin and Cyclophosphamide in people with Triple Negative Breast Cancer, run by Russian Academy of Medical Sciences.
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 14 inclusion and 16 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: status not confirmed, as of the sponsor's last update on 22 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Mona Frolova (+79031990675, mona.frolova@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
• Pathological complete response rate (time frame: After 24 weeks of neoadjuvant chemotherapy and surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 Feb 2016.