Anatomic Stage II Breast Cancer AJCC v8Early Phase 1NCT03132467
Durvalumab and Tremelimumab Before Surgery in Treating Patients With Hormone Receptor Positive, HER2 Negative Stage II-III Breast Cancer
A Early Phase 1 study testing Durvalumab and Tremelimumab in people with Anatomic Stage II Breast Cancer AJCC v8 and Anatomic Stage IIA Breast Cancer AJCC v8, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
This early phase I trial studies the side effects of durvalumab and tremelimumab before surgery in treating patients with hormone receptor positive, HER2 negative stage II-III breast cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIA Breast Cancer AJCC v8, Anatomic Stage IIB Breast Cancer AJCC v8
- What is being tested?
- Durvalumab and Tremelimumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Jun 2017to 20 May 2024
- Phase
- Early Phase 1
- 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
- Written informed consent and any locally-required authorization (e.g., Health Insurance Portability and Accountability Act [HIPAA]) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Hormone receptor positive (defined as estrogen receptor [ER] and/or progesterone receptor [PR] positive), HER2 negative breast cancer that is clinically staged II-III with no known metastatic disease. ER and/or PR defined as positive if expression > 10% by immunohistochemistry (IHC). HER2 negative or non-amplified as determined by the current American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) criteria which are as follows: HER2 testing by immunohistochemistry (IHC) as 0 or 1+. If HER2 is 2+, ISH (in situ hybridization) must be performed. HER2 is positive if: IHC 3+ based on circumferential membrane staining that is complete, intense ISH positive based on: 1) Single-probe average HER2 copy number >= 6.0 signals/cell, 2) Dual-probe HER2/CEP17 ratio >= 2.0; c,e with an average HER2 copy number >= 4.0 signals/cell, 3) Dual-probe HER2/CEP17 ratio >= 2.0; c,e with an average HER2 copy number < 4.0 signals/cell, 4) Dual-probe HER2/CEP17 ratio < 2.0; c,e with an average HER2 copy number >= 6.0 signals/cell
- Chemotherapy is planned for the patient in the neoadjuvant setting
- Hemoglobin >= 9.0 g/dL
- Absolute neutrophil count (ANC) >=1.5 x 10^9/L (>= 1500 per mm^3)
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- Platelet count >= 100 x 10^9/L (>= 100,000 per mm^3)
- Serum bilirubin =< 1.5 x institutional upper limit of normal (ULN). This will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only upon treating physician, principal investigators (PI) or co-PIs approval
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be =< 5 x ULN
- Creatinine clearance (CL) > 40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance
- Female subjects must either be of non-reproductive potential (i.e., post-menopausal by history: >= 60 years old and no menses for >= 1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative urine pregnancy test upon study entry
- Subject 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
Who cannot join
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
- Participation in another clinical study with an investigational product during the last 1 month prior to initiation of therapy
- Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an anti-CTLA4, including tremelimumab
- History of another primary malignancy except for:
- Malignancy treated with curative intent and with no known active disease >= 5 years before the first dose of study drug and of low potential risk for recurrence
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
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- Adequately treated carcinoma in situ without evidence of disease e.g., cervical cancer in situ
- Has received therapy for this current diagnosis of breast cancer including endocrine therapy or chemotherapy
- A single QT interval corrected for heart rate (QTc) >= 470 ms. If an electrocardiogram (ECG) is interpreted to be a prolonged QT interval, 2 additional ECGs will be obtained and the PI will then evaluate all three ECGs and determine whether the patient should be excluded. Mean QT interval corrected for heart rate (QTc) >= 470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia's correction
- Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab or tremelimumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid
- Active or prior documented autoimmune disease within the past 2 years
- NOTE: Subjects with vitiligo, Graves disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded
- Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
- History of primary immunodeficiency
- History of allogeneic organ transplant
- History of hypersensitivity to durvalumab or tremelimumab or any excipient
- History of hypersensitivity to the combination or comparator agent (if applicable)
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent
- Known history of previous clinical diagnosis of tuberculosis
- History of leptomeningeal carcinomatosis
- Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab or tremelimumab
- Female subjects who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control
- Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
- Subjects with uncontrolled seizures
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Pilot Pre-Surgical Study Evaluating Anti-PD-L1 Antibody (Durvalumab [MEDI4736]) Plus Anti-CTLA-4 Antibody (Tremelimumab) in Patients With Hormone Receptor Positive, HER2 Negative Breast Cancer
This early phase I trial studies the side effects of durvalumab and tremelimumab before surgery in treating patients with hormone receptor positive, HER2 negative stage II-III breast cancer. Immunotherapy with monoclonal antibodies, such as durvalumab and tremelimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
Read the detailed description
PRIMARY OBJECTIVES:
- To evaluate the feasibility of enrolling patients with hormone receptor positive (HR+)/human epidermal growth factor receptor negative (HER2-) breast cancer onto a trial evaluating investigational agents prior to initiating standard neoadjuvant chemotherapy.
II. To evaluate the safety and tolerability of tremelimumab plus durvalumab in patients with HR+/HER2- breast cancer.
SECONDARY OBJECTIVES:
- To assess immunologic/molecular responses to tremelimumab and durvalumab in patients with HR+/HER2- breast cancer who receive the combination therapy.
EXPLORATORY OBJECTIVES:
- To evaluate the pathologic response in patients with HR+/HER2- breast cancer receiving tremelimumab plus durvalumab prior to initiating standard neoadjuvant chemotherapy.
OUTLINE:
Patients receive tremelimumab intravenously (IV) over 1 hour and durvalumab IV over 1 hour on day 1. Treatment repeats every 4 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo a biopsy and receive standard of care neoadjuvant chemotherapy before undergoing surgery.
After completion of study treatment, patients are followed up until the time of surgery.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DurvalumabBiological
Also called Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736
Given IV
TremelimumabBiological
Also called Anti-CTLA4 Human Monoclonal Antibody CP-675,206, CP-675, CP-675,206, CP-675206
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (tremelimumab, durvalumab) | Experimental | Patients receive tremelimumab IV over 1 hour and durvalumab IV over 1 hour on day 1. Treatment repeats every 4 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo a biopsy and receive standard of care neoadjuvant chemotherapy before undergoing surgery. Receives: Biological: Durvalumab; Biological: Tremelimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility of Enrolling 15 Patients Within 2 Years
Feasibility established if all 15 patients enroll within 12 months of starting the study. The start date for measuring feasibility will be the date the first patient is screened.
Measured: Up to 2 years
Safety and Tolerability of Tremelimumab Plus Durvalumab in Participants With HR+/HER2 Neg Breast Cancer.
To evaluate the safety and tolerability of tremelimumab plus durvalumab in patients with HR+/HER2 neg breast cancer. Adverse events per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event [CTCAE] v4.03.
Measured: 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2017
- Study start13 Jun 2017
- Primary completion31 Jan 2019
- Study completion20 May 2024
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 Anatomic Stage II Breast Cancer AJCC v8Studies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Jennifer K Litton, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03132467
- Sponsor's protocol ID
- 2016-0902
- Other IDs
- NCI-2018-01189, 2016-0902
- Status last verified
- May 2024
- First submitted
- 25 Apr 2017
- Last updated
- 5 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Pre-Surgical Study Evaluating Anti-PD-L1 Antibody (Durvalumab [MEDI4736]) Plus Anti-CTLA-4 Antibody (Tremelimumab) in Patients With Hormone Receptor Positive, HER2 Negative Breast Cancer
- ClinicalTrials.gov ID
- NCT03132467
- Acronym / sponsor ID
- 2016-0902
- Conditions
- Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIA Breast Cancer AJCC v8, Anatomic Stage IIB Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8, Anatomic Stage IIIB Breast Cancer AJCC v8
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 13 Jun 2017 (actual)
- Primary completion
- 31 Jan 2019 (actual)
- Study completion
- 20 May 2024 (actual)
- First posted
- 27 Apr 2017 (actual)
- Results
- Posted 17 Feb 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This early phase I trial studies the side effects of durvalumab and tremelimumab before surgery in treating patients with hormone receptor positive, HER2 negative stage II-III breast cancer. Immunotherapy with monoclonal antibodies, such as durvalumab and tremelimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
Detailed description
PRIMARY OBJECTIVES:
- To evaluate the feasibility of enrolling patients with hormone receptor positive (HR+)/human epidermal growth factor receptor negative (HER2-) breast cancer onto a trial evaluating investigational agents prior to initiating standard neoadjuvant chemotherapy.
II. To evaluate the safety and tolerability of tremelimumab plus durvalumab in patients with HR+/HER2- breast cancer.
SECONDARY OBJECTIVES:
- To assess immunologic/molecular responses to tremelimumab and durvalumab in patients with HR+/HER2- breast cancer who receive the combination therapy.
EXPLORATORY OBJECTIVES:
- To evaluate the pathologic response in patients with HR+/HER2- breast cancer receiving tremelimumab plus durvalumab prior to initiating standard neoadjuvant chemotherapy.
OUTLINE:
Patients receive tremelimumab intravenously (IV) over 1 hour and durvalumab IV over 1 hour on day 1. Treatment repeats every 4 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo a biopsy and receive standard of care neoadjuvant chemotherapy before undergoing surgery.
After completion of study treatment, patients are followed up until the time of surgery.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (tremelimumab, durvalumab) | Experimental | Biological: Durvalumab, Biological: TremelimumabPatients receive tremelimumab IV over 1 hour and durvalumab IV over 1 hour on day 1. Treatment repeats every 4 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo a biopsy and receive standard of care neoadjuvant chemotherapy before undergoing surgery. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Written informed consent and any locally-required authorization (e.g., Health Insurance Portability and Accountability Act [HIPAA]) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Hormone receptor positive (defined as estrogen receptor [ER] and/or progesterone receptor [PR] positive), HER2 negative breast cancer that is clinically staged II-III with no known metastatic disease. ER and/or PR defined as positive if expression > 10% by immunohistochemistry (IHC). HER2 negative or non-amplified as determined by the current American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) criteria which are as follows: HER2 testing by immunohistochemistry (IHC) as 0 or 1+. If HER2 is 2+, ISH (in situ hybridization) must be performed. HER2 is positive if: IHC 3+ based on circumferential membrane staining that is complete, intense ISH positive based on: 1) Single-probe average HER2 copy number >= 6.0 signals/cell, 2) Dual-probe HER2/CEP17 ratio >= 2.0; c,e with an average HER2 copy number >= 4.0 signals/cell, 3) Dual-probe HER2/CEP17 ratio >= 2.0; c,e with an average HER2 copy number < 4.0 signals/cell, 4) Dual-probe HER2/CEP17 ratio < 2.0; c,e with an average HER2 copy number >= 6.0 signals/cell
- Chemotherapy is planned for the patient in the neoadjuvant setting
- Hemoglobin >= 9.0 g/dL
Key exclusion criteria (24 listed)
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
- Participation in another clinical study with an investigational product during the last 1 month prior to initiation of therapy
- Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an anti-CTLA4, including tremelimumab
- History of another primary malignancy except for:
- Has received therapy for this current diagnosis of breast cancer including endocrine therapy or chemotherapy
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 |
|---|---|---|
| DurvalumabAlso: Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736Given IV | Biological | Treatment (tremelimumab, durvalumab) |
| TremelimumabAlso: Anti-CTLA4 Human Monoclonal Antibody CP-675,206, CP-675, CP-675,206, CP-675206Given IV | Biological | Treatment (tremelimumab, durvalumab) |
Primary outcome
Feasibility of Enrolling 15 Patients Within 2 Years
Time frame: Up to 2 years
Feasibility established if all 15 patients enroll within 12 months of starting the study. The start date for measuring feasibility will be the date the first patient is screened.
Safety and Tolerability of Tremelimumab Plus Durvalumab in Participants With HR+/HER2 Neg Breast Cancer.
Time frame: 2 months
To evaluate the safety and tolerability of tremelimumab plus durvalumab in patients with HR+/HER2 neg breast cancer. Adverse events per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event [CTCAE] v4.03.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- University of Texas MD Anderson Cancer Center 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.
Jennifer K Litton principal investigator
M.D. Anderson Cancer Center
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 Durvalumab and Tremelimumab in people with Anatomic Stage II Breast Cancer AJCC v8 and Anatomic Stage IIA Breast Cancer AJCC v8, run by M.D. Anderson Cancer Center 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 12 inclusion and 24 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 5 Jun 2024. 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?
Yes. Results are posted in the registry (first posted 17 Feb 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?
Feasibility of Enrolling 15 Patients Within 2 Years (time frame: Up to 2 years). The study lists 2 primary outcomes in all. 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 5 Jun 2024.