Breast NeoplasmsPhase 1/2NCT02489448
Neoadjuvant MEDI4736 Concomitant With Weekly Nab-paclitaxel and Dose-dense AC for Stage I-III Triple Negative Breast Cancer
A Phase 1/2 study testing MEDI4736 in people with Breast Neoplasms, run by Yale University at 1 site in United States.
Trial summary
The purpose of the study is to address the following hypotheses: (i) Anti-PD-L1 therapy with MEDI4736 administered concomitantly with weekly nab-paclitaxel followed by MEDI4736 concomitant with ddAC neoadjuvant chemotherapy will induce higher pathologic complete response (pCR) rate (>55%) in triple negative breast… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Neoplasms
- What is being tested?
- MEDI4736
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 68 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2015to 2 Aug 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Newly diagnosed histologically confirmed stage I-III, ER, PR and HER2 negative invasive breast cancer as defined by the ASCO CAP guidelines for whom systemic chemotherapy would be indicated based on physician judgment following standard NCCN practice guidelines.
- Willing and able to provide written informed consent for voluntary participation in the trial.
- Willing to undergo a baseline tumor core needle biopsy and blood draws for correlative science studies.
- Eighteen years of age or older on the day of signing informed consent.
- Female subjects must either be of non-reproductive potential or must have a negative urine or serum pregnancy test upon study entry.
- Patients should have adequate organ function to tolerate chemotherapy, as defined by:
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- peripheral granulocyte count of > 1,500/mm3
- platelet count > 100,000/mm3
- hemoglobin >9 g/dL
- total bilirubin < 1.5 x upper limit of normal (ULN)
- aspartate aminotransferase (AST) and alanine aminotransferase (ALT) each < 1.5 x ULN
- serum creatinine < 1.5 x ULN or serum creatinine clearance < 50mL/min
- INR/PT/PTT each < 1.5 x ULN
- TSH within normal limits
Who cannot join
- Patients who underwent partial excisional biopsy or lumpectomy, segmental mastectomy or modified radical mastectomy or sentinel node.
- Patients for whom anthracycline, paclitaxel or antibody therapies are contraindicated.
- Patients with active autoimmune disease or documented autoimmune disease within 2 years. Patients with hypothyroidism that is clinically stable and have normal TSH levels with hormone replacement, or patients with vitiligo or psoriasis not requiring treatment remain eligible for the study.
- Active or prior documented inflammatory bowel disease (Crohn's disease, ulcerative colitis).
- Patients with known active hepatitis B or C or HIV infection or with history of tuberculosis.
Trial locations and contacts
1 site in 1 country.
United States1 site
Yale School of Medicine
New Haven, Connecticut, 06511
About this study
Official title: Single Arm Neoadjuvant Phase I/II Study of MEDI4736 (Anti-PD-L1 Antibody) Concomitant With Weekly Nab-paclitaxel and Dose-dense Doxorubicin/Cyclophosphamide (ddAC) Chemotherapy for Clinical Stage I-III Triple Negative Breast Cancer
The purpose of the study is to address the following hypotheses: (i) Anti-PD-L1 therapy with MEDI4736 administered concomitantly with weekly nab-paclitaxel followed by MEDI4736 concomitant with ddAC neoadjuvant chemotherapy will induce higher pathologic complete response (pCR) rate (>55%) in triple negative breast cancer than historical pCR rates (30-40%) observed with chemotherapy alone. (ii) MEDI4736 can be safely co-administered at full dose with sequential with nab-paclitaxel (100mg/m2) and ddAC (60 mg/m2 and 600 mg/m2 respectively).
Read the detailed description
The primary objective of the Phase I portion of the trial is to assess the safety of MEDI4736 combined with chemotherapy and determine if full dose of MEDI4736 can be administered concomitantly with full dose weekly nab-paclitaxel followed by dose-dense AC chemotherapies, respectively.
The primary objective of the Phase II portion of the study is to estimate the pCR rate with MEDI4736 in combination with weekly nab-paclitaxel x 12 treatments followed by MEDI4736 in combination with ddAC x 4 treatments for estrogen receptor (ER), progesterone receptor (PR) and HER2 negative (triple negative, TNBC), clinical stage I-III breast cancer. Pathologic complete response is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (i.e. ypT0/Tis ypN0).
Secondary objectives include: to assess the safety and toxicity of adding anti-PD-L1 antibody, MEDI4736 to standard of care neoadjuvant chemotherapy in the Phase II portion of the trial. The study will also monitor for events of special clinical interest with a suspected auto-immunologic etiology including grade ≥3 colitis, hyperthyroidism, hypophysitis, hypothyroidism, pneumonitis, rash and anti-drug-antibody (ADA) immune complex disease (manifested by symptoms of arthralgias, abdominal pain, back pain, and vasculitis).
Exploratory objectives include: to assess correlation between response to therapy and immune parameters of the tumor at baseline and post-treatment in patients who have residual cancer after therapy.
- Conditions
- Breast Neoplasms
- Being tested
- MEDI4736
- Keywords
- Breast Cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MEDI4736Drug
Also called tremelimumab, anti-PD-L1 antibody
The investigational product is MEDI4736 which will be supplied in glass vials containing 500 mg of liquid solution at a concentration of 50 mg/mL for intravenous (IV) administration.
Routine, standard of care chemotherapy will be given together with the investigational product and will include weekly nab-paclitaxel x12 treatments followed by every two-week doxorubicin, cyclophosphamide (ddAC) x 4 treatments.
| Study group | Role | What they receive |
|---|---|---|
| MEDI4736 | Experimental | The investigational product is MEDI4736 which will be supplied in glass vials containing 500 mg of liquid solution at a concentration of 50 mg/mL for intravenous (IV) administration.
Routine, standard of care chemotherapy will be given together with the investigational product and will include weekly nab-paclitaxel x12 treatments followed by every two-week doxorubicin, cyclophosphamide (ddAC) x 4 treatments. Receives: Drug: MEDI4736 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathologic Complete Response (pCR)
Pathologic response will be assessed in the surgically resected cancer and lymph nodes after completion of all chemotherapy by the local pathologist as part of routine care. Pathologic complete response is defined as no invasive cancer in the resected breast tissue and lymph nodes (ypT0/Tis, ypN0).
The outcome was changed from 19 weeks at the time of results entry as the treatment period was actually 20 weeks and the outcome was assessed 4-6 weeks after treatment when surgery took place.
Measured: Up to 26 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jul 2015 (estimated)
- Study startNov 2015
- Primary completion15 Jun 2021
- Study completion2 Aug 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast NeoplasmsStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 68 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lajos Pusztai, MD, D. Phil., Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02489448
- Sponsor's protocol ID
- 1409014537
- Status last verified
- Oct 2022
- First submitted
- 1 Jul 2015
- Last updated
- 26 Oct 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single Arm Neoadjuvant Phase I/II Study of MEDI4736 (Anti-PD-L1 Antibody) Concomitant With Weekly Nab-paclitaxel and Dose-dense Doxorubicin/Cyclophosphamide (ddAC) Chemotherapy for Clinical Stage I-III Triple Negative Breast Cancer
- ClinicalTrials.gov ID
- NCT02489448
- Acronym / sponsor ID
- 1409014537
- Conditions
- Breast Neoplasms
- Keywords
- Breast Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 68 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Study start
- Nov 2015
- Primary completion
- 15 Jun 2021 (actual)
- Study completion
- 2 Aug 2021 (actual)
- First posted
- 3 Jul 2015 (estimated)
- Results
- Posted 26 Oct 2022
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 the study is to address the following hypotheses: (i) Anti-PD-L1 therapy with MEDI4736 administered concomitantly with weekly nab-paclitaxel followed by MEDI4736 concomitant with ddAC neoadjuvant chemotherapy will induce higher pathologic complete response (pCR) rate (>55%) in triple negative breast cancer than historical pCR rates (30-40%) observed with chemotherapy alone. (ii) MEDI4736 can be safely co-administered at full dose with sequential with nab-paclitaxel (100mg/m2) and ddAC (60 mg/m2 and 600 mg/m2 respectively).
Detailed description
The primary objective of the Phase I portion of the trial is to assess the safety of MEDI4736 combined with chemotherapy and determine if full dose of MEDI4736 can be administered concomitantly with full dose weekly nab-paclitaxel followed by dose-dense AC chemotherapies, respectively.
The primary objective of the Phase II portion of the study is to estimate the pCR rate with MEDI4736 in combination with weekly nab-paclitaxel x 12 treatments followed by MEDI4736 in combination with ddAC x 4 treatments for estrogen receptor (ER), progesterone receptor (PR) and HER2 negative (triple negative, TNBC), clinical stage I-III breast cancer. Pathologic complete response is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (i.e. ypT0/Tis ypN0).
Secondary objectives include: to assess the safety and toxicity of adding anti-PD-L1 antibody, MEDI4736 to standard of care neoadjuvant chemotherapy in the Phase II portion of the trial. The study will also monitor for events of special clinical interest with a suspected auto-immunologic etiology including grade ≥3 colitis, hyperthyroidism, hypophysitis, hypothyroidism, pneumonitis, rash and anti-drug-antibody (ADA) immune complex disease (manifested by symptoms of arthralgias, abdominal pain, back pain, and vasculitis).
Exploratory objectives include: to assess correlation between response to therapy and immune parameters of the tumor at baseline and post-treatment in patients who have residual cancer after therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MEDI4736 | Experimental | Drug: MEDI4736The investigational product is MEDI4736 which will be supplied in glass vials containing 500 mg of liquid solution at a concentration of 50 mg/mL for intravenous (IV) administration. Routine, standard of care chemotherapy will be given together with the investigational product and will include weekly nab-paclitaxel x12 treatments followed by every two-week doxorubicin, cyclophosphamide (ddAC) x 4 treatments. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Newly diagnosed histologically confirmed stage I-III, ER, PR and HER2 negative invasive breast cancer as defined by the ASCO CAP guidelines for whom systemic chemotherapy would be indicated based on physician judgment following standard NCCN practice guidelines.
- Willing and able to provide written informed consent for voluntary participation in the trial.
- Willing to undergo a baseline tumor core needle biopsy and blood draws for correlative science studies.
- Eighteen years of age or older on the day of signing informed consent.
- Female subjects must either be of non-reproductive potential or must have a negative urine or serum pregnancy test upon study entry.
Key exclusion criteria (5 listed)
- Patients who underwent partial excisional biopsy or lumpectomy, segmental mastectomy or modified radical mastectomy or sentinel node.
- Patients for whom anthracycline, paclitaxel or antibody therapies are contraindicated.
- Patients with active autoimmune disease or documented autoimmune disease within 2 years. Patients with hypothyroidism that is clinically stable and have normal TSH levels with hormone replacement, or patients with vitiligo or psoriasis not requiring treatment remain eligible for the study.
- Active or prior documented inflammatory bowel disease (Crohn's disease, ulcerative colitis).
- Patients with known active hepatitis B or C or HIV infection or with history of tuberculosis.
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 |
|---|---|---|
| MEDI4736Also: tremelimumab, anti-PD-L1 antibodyThe investigational product is MEDI4736 which will be supplied in glass vials containing 500 mg of liquid solution at a concentration of 50 mg/mL for intravenous (IV) administration. Routine, standard of care chemotherapy will be given together with the investigational product and will include weekly nab-paclitaxel x12 treatments followed by every two-week doxorubicin, cyclophosphamide (ddAC) x 4 treatments. | Drug | MEDI4736 |
Primary outcome
Pathologic Complete Response (pCR)
Time frame: Up to 26 weeks
Pathologic response will be assessed in the surgically resected cancer and lymph nodes after completion of all chemotherapy by the local pathologist as part of routine care. Pathologic complete response is defined as no invasive cancer in the resected breast tissue and lymph nodes (ypT0/Tis, ypN0). The outcome was changed from 19 weeks at the time of results entry as the treatment period was actually 20 weeks and the outcome was assessed 4-6 weeks after treatment when surgery took place.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Lajos Pusztai, MD, D. Phil. principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing MEDI4736 in people with Breast Neoplasms, run by Yale University at 1 site in United States.
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 5 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 26 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Yes. Results are posted in the registry (first posted 26 Oct 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Pathologic Complete Response (pCR) (time frame: Up to 26 weeks). 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 26 Oct 2022.