Breast Cancer FemaleEarly Phase 1NCT04088032
Neoadjuvant Study of Abemaciclib, Durvalumab, and an Aromatase Inhibitor Early Stage Breast Cancer
A Early Phase 1 study testing Abemaciclib, durvalumab and aromatase inhibitor in people with Breast Cancer Female and Locally Advanced Breast Cancer, run by Alison Stopeck at 1 site in United States.
Trial summary
The purpose of this study is to test the efficacy, safety and tolerability of a combination of immunotherapy and anticancer drugs presurgery in patients with hormone-receptor positive breast cancer. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer Female, Locally Advanced Breast Cancer, Hormone Receptor Positive Malignant Neoplasm of Breast
- What is being tested?
- Abemaciclib, durvalumab and aromatase inhibitor
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2019to 31 Dec 2020
- Phase
- Early Phase 1
- 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
- A signed, written informed consent will be obtained from the subject prior to performing any protocol-related procedures, including screening evaluations.
- Postmenopausal women age ≥ 18 years at time of study entry. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
- Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
- Women <50 years of age receiving luteinising hormone-releasing hormone (LHRH) agonist for ovarian suppression are also eligible for the study but must initiate LHRH agonist therapy at least 2 weeks prior to starting on study intervention.
- Women ≥ 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
- Histologically confirmed estrogen and/or progesterone positive invasive breast cancer, defined as either estrogen and/or progesterone receptor (ER/PR) staining >10%, AND Human Epidermal Growth Factor Receptor 2 (HER2) negative by either Immunohistochemistry (IHC) or Fluorescent in situ Hybridization (FISH).
Show all 18Show fewer
- Clinical stage II-III disease with no clinical or radiologic evidence of metastatic disease. Patients must have a measurable primary breast lesion as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guidelines.
- Eastern Cooperative Oncology Group (ECOG) status < 1.
- Patient must be able to swallow pills.
- Adequate organ and marrow function as defined below and in Table 1:
- Hemoglobin ≥ 9 g/deciliter
- Absolute neutrophil count ≥ 1,500/mm3
- Platelet count ≥ 100,000/mm3
- Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2 × institutional upper limit of normal (ULN)
- Bilirubin ≤ 1.5 × ULN; for subjects with documented/suspected Gilbert's disease, bilirubin ≤ 2 × ULN
- Creatinine clearance ≥ 50 mL/min as determined by the Cockcroft-Gault equation, or creatinine ≤1.5 x ULN
- Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
- Must have a life expectancy of at least 12 weeks.
Who cannot join
- Any serious preexisting medical condition(s) that would place the patient at increased risk for toxicities including interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, history of major surgical resection involving the stomach or small bowel.
- Body weight < 30 kg (or 66.5 lbs.). If during the study, the patient's weight drops to < 30 Kg (or 66.5 lbs), they will be withdrawn from the study.
- Females who are pregnant or lactating.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, severe active peptic ulcer disease or gastritis, or psychiatric illness/social situations that would limit compliance with study requirement or compromise the ability of the subject to give written informed consent
- Active or prior documented autoimmune disease within the past 2 years. NOTE: Subjects with vitiligo, Grave's disease, Hashimoto's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are eligible
- History of significant cardiac disease including heart failure, ventricular arrhythmia, or prolonged QT syndrome.
Show all 22Show fewer
- Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis, or a preexisting chronic condition resulting in baseline ≥ Grade 2 diarrhea.)
- History of primary immunodeficiency, or subjects who are known to be HIV (Human Immunodeficiency Virus ) positive
- History of organ transplant that requires use of immunosuppressives
- Known allergy or reaction to any of the study drugs.
- Other invasive malignancy within 2 years except for noninvasive malignancies such as cervical carcinoma in situ, non-melanomatous carcinoma of the skin or ductal carcinoma in situ of the breast that has/have been surgically cured
- Major surgical procedure (as defined by the investigator) within 30 days prior to the first dose of study drugs or still recovering from prior surgery
- Known history of tuberculosis
- Subjects who are known to be hepatitis B or C positive
- History of prior therapy with a checkpoint (PD-L1/PD-1) including durvalumab or CDK4/6 inhibitor
- History of prior ipsilateral radiation therapy to the cancer-affected breast
- History of prior therapy with an investigational anticancer therapy within 6 weeks prior to the first dose of study drugs
- Prior chemotherapy or aromatase inhibitor therapy for breast cancer
- Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal, topical, and inhaled corticosteroids or systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent
- Patients who must take strong cytochrome cytochrome P450 (CYP3A) inhibitors such as clarithromycin, diltiazem, verapamil, itraconazole, or ketoconazole
- Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab
- Concurrent enrollment in another therapeutic clinical study
Trial locations and contacts
1 site in 1 country.
United States1 site
Stony Brook University Cancer Center
Stony Brook, New York, 11794
About this study
Official title: A Pilot Neoadjuvant Clinical Trial of Combination Therapy With Abemaciclib, Durvalumab (MEDI4736), and an Aromatase Inhibitor in Locally Advanced Hormone Receptor Positive Breast Cancer
The purpose of this study is to test the efficacy, safety and tolerability of a combination of immunotherapy and anticancer drugs presurgery in patients with hormone-receptor positive breast cancer.
Read the detailed description
The primary hypothesis is that a Programmed death-ligand 1 (PD-L1) immune checkpoint inhibitor combined with a Cyclin-dependent kinase 4/6 (CDK4/6) inhibitor will be well tolerated in early stage, hormone receptor positive (HR+) breast cancer patients treated with neoadjuvant endocrine therapy (NET). The secondary hypothesis and biomarker based endpoint is that patients with HR positive locally advanced breast cancer with low to intermediate stromal tumor-infiltrating lymphocytes (TILs) will demonstrate an increase in stromal TILs following NET when combined with abemaciclib and durvalumab for 4 cycles (16 weeks).
- Conditions
- Breast Cancer Female, Locally Advanced Breast Cancer, Hormone Receptor Positive Malignant Neoplasm of Breast
- Being tested
- Abemaciclib, durvalumab and aromatase inhibitor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Abemaciclib, durvalumab and aromatase inhibitorDrug
Subjects will receive standard therapy with an aromatase inhibitor (exemestane, anastrozole, or letrozole), combined with the experimental treatment of abemaciclib and durvalumab
| Study group | Role | What they receive |
|---|---|---|
| Active | Experimental | Experimental treatment Receives: Drug: Abemaciclib, durvalumab and aromatase inhibitor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
The primary endpoints will be safety and tolerability of the study intervention
Measured: Through study completion, up to 24 weeks
Secondary outcomes (2)
Pathologic response at surgery
Pathologic response at surgery by Preoperative Endocrine Prognostic Index (PEPI) score
Measured: At the time of definitive surgery
Pathologic response at surgery
Pathologic response at surgery by change in Ki-67% from pre and surgical biopsies
Measured: At the time of definitive surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2019
- Study start1 Oct 2019 (estimated)
- Primary completion31 Dec 2020 (estimated)
- Study completion31 Dec 2020 (estimated)
Why it stopped: Per sponsor
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast Cancer FemaleStudies 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alison Stopeck
- Sponsor type
- University, hospital or other
- Collaborators
- Eli Lilly and Company, AstraZeneca
- Responsible party
- Sponsor-investigator, Alison Stopeck, Stony Brook University
- Investigators
- Alison Stopeck, MD, Study director, Stony Brook UniversityLea Baer, MD, Principal investigator, Stony Brook University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04088032
- Sponsor's protocol ID
- 2019-00174 Neoadj Breast Pilot
- Other IDs
- 2019
- Status last verified
- Jul 2020
- First submitted
- 10 Sep 2019
- Last updated
- 16 Jul 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Neoadjuvant Clinical Trial of Combination Therapy With Abemaciclib, Durvalumab (MEDI4736), and an Aromatase Inhibitor in Locally Advanced Hormone Receptor Positive Breast Cancer
- ClinicalTrials.gov ID
- NCT04088032
- Acronym / sponsor ID
- 2019-00174 Neoadj Breast Pilot
- Conditions
- Breast Cancer Female, Locally Advanced Breast Cancer, Hormone Receptor Positive Malignant Neoplasm of Breast
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Per sponsor
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Alison StopeckUniversity, hospital or other
- Collaborators
- Eli Lilly and Company, AstraZeneca
- Study start
- 1 Oct 2019 (estimated)
- Primary completion
- 31 Dec 2020 (estimated)
- Study completion
- 31 Dec 2020 (estimated)
- First posted
- 12 Sep 2019 (actual)
- 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 test the efficacy, safety and tolerability of a combination of immunotherapy and anticancer drugs presurgery in patients with hormone-receptor positive breast cancer.
Detailed description
The primary hypothesis is that a Programmed death-ligand 1 (PD-L1) immune checkpoint inhibitor combined with a Cyclin-dependent kinase 4/6 (CDK4/6) inhibitor will be well tolerated in early stage, hormone receptor positive (HR+) breast cancer patients treated with neoadjuvant endocrine therapy (NET). The secondary hypothesis and biomarker based endpoint is that patients with HR positive locally advanced breast cancer with low to intermediate stromal tumor-infiltrating lymphocytes (TILs) will demonstrate an increase in stromal TILs following NET when combined with abemaciclib and durvalumab for 4 cycles (16 weeks).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Active | Experimental | Drug: Abemaciclib, durvalumab and aromatase inhibitorExperimental treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- A signed, written informed consent will be obtained from the subject prior to performing any protocol-related procedures, including screening evaluations.
- Postmenopausal women age ≥ 18 years at time of study entry. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
- Histologically confirmed estrogen and/or progesterone positive invasive breast cancer, defined as either estrogen and/or progesterone receptor (ER/PR) staining >10%, AND Human Epidermal Growth Factor Receptor 2 (HER2) negative by either Immunohistochemistry (IHC) or Fluorescent in situ Hybridization (FISH).
- Clinical stage II-III disease with no clinical or radiologic evidence of metastatic disease. Patients must have a measurable primary breast lesion as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guidelines.
- Eastern Cooperative Oncology Group (ECOG) status < 1.
Key exclusion criteria (22 listed)
- Any serious preexisting medical condition(s) that would place the patient at increased risk for toxicities including interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, history of major surgical resection involving the stomach or small bowel.
- Body weight < 30 kg (or 66.5 lbs.). If during the study, the patient's weight drops to < 30 Kg (or 66.5 lbs), they will be withdrawn from the study.
- Females who are pregnant or lactating.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, severe active peptic ulcer disease or gastritis, or psychiatric illness/social situations that would limit compliance with study requirement or compromise the ability of the subject to give written informed consent
- Active or prior documented autoimmune disease within the past 2 years. NOTE: Subjects with vitiligo, Grave's disease, Hashimoto's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are eligible
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 |
|---|---|---|
| Abemaciclib, durvalumab and aromatase inhibitorSubjects will receive standard therapy with an aromatase inhibitor (exemestane, anastrozole, or letrozole), combined with the experimental treatment of abemaciclib and durvalumab | Drug | Active |
Primary outcome
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time frame: Through study completion, up to 24 weeks
The primary endpoints will be safety and tolerability of the study intervention
2 secondary outcomes
Pathologic response at surgery
Time frame: At the time of definitive surgery
Pathologic response at surgery
Time frame: At the time of definitive surgery
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jul 2020.
- Individual participant dataSharing planned: No
Related trials for Breast Cancer Female
Recruiting
Decision Support for Chemoprevention
Breast Cancer
Not yet recruiting
Geriatric Oncology Assessment and Coping Skills Training for Older Women on Aromatase Inhibitor Therapy
Breast Cancer, Hormone Receptor Positive, Aromatase Inhibitor-Associated Arthralgia
Recruiting
The Vanguard Study: Testing a New Way to Screen for Cancer
Bladder Carcinoma, Breast Carcinoma
Active, not recruitingPhase 1
A Phase 1 Study of XL309 (ISM3091) Alone and in Combination in Participants With Advanced Solid Tumors
Advanced Solid Tumor
RecruitingPhase 1
A Phase I Study of CG-7321 Monotherapy or Combination Therapy in Advanced Solid Tumors
Advanced Solid Tumors, Breast Cancer
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.
Alison Stopeck, MD study director
Stony Brook University
Lea Baer, MD principal investigator
Stony Brook University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Abemaciclib, durvalumab and aromatase inhibitor in people with Breast Cancer Female and Locally Advanced Breast Cancer, run by Alison Stopeck 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 18 inclusion and 22 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: withdrawn, as of the sponsor's last update on 16 Jul 2020. 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 phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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 was withdrawn before enrolling participants, so there are no results.
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?
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 (time frame: Through study completion, up to 24 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 16 Jul 2020.