Metastatic Breast CancerNCT02563925
Brain Irradiation and Tremelimumab in Metastatic Breast Cancer
A study testing Brain radiotherapy or Stereotactic Radiosurgery, Tremelimumab and HER2 directed therapy in people with Metastatic Breast Cancer, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
Trial summary
The purpose of this study is to see if the combination of tremelimumab and durvalumab with brain radiation therapy can help treat this type of breast cancer that has spread to the brain. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Metastatic Breast Cancer
- What is being tested?
- Brain radiotherapy or Stereotactic Radiosurgery, Tremelimumab and HER2 directed therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Sep 2015to 14 Jul 2021
- Phase
- Interventional
- 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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of CNS metastases for whom SRS or WBRT is indicated, as determined by radiation oncologist assessment
- Age 18 and older at the time of consent
- Written informed consent and authorization obtained from the subject/HIPAA-appointed legal representative prior to performing any protocol-related procedures including screening evaluations
- ECOG performance of 0-2 with anticipated life expectancy of ≥12 weeks
- Histologically or cytologically confirmed invasive breast cancer that is HER2-positive (3+ by IHC and/or >2.0 by FISH) if concurrent HER2-directed therapy is planned;
- Non-CNS progression of disease as assessed by the investigator/treating physician, for which a change in systemic therapy is planned OR achievement of stable or responsive non-CNS disease for which a holiday from the current systemic therapy is planned, as assessed by the investigator/treating physician.
Show all 22Show fewer
- Measurable non-CNS disease, defined by RECIST1.1 criteria
- Recovered from all toxicities associated with prior treatment, to acceptable baseline status or grade 1 or less (for lab toxicities see below limits for inclusion,), except for toxicities not considered a safety risk, such as alopecia or vitiligo. Peripheral neuropathy must be grade 2 or less
- Adequate organ and marrow function, as defined below:
- platelets ≥ 75x 103/μL;
- absolute neutrophil count (ANC) ≥ 1,000/μL;
- hemoglobin ≥ 9.0 g/dL;
- total bilirubin ≤1.5 x ULN (upper limit of normal) except subject with documented Gilbert's syndrome (≤5 x ULN) or liver metastasis, who must have a baseline total bilirubin ≤3.0 mg/dL;
- AST and ALT ≤ 3 x ULN, unless associated with hepatobiliary metastases, in that case ≤5 x ULN
- serum creatinine ≤ 2 mg/dL (or glomerular filtration rate ≥ 50 ml/min as determined by the Cockcroft-Gault equation);
- Negative hepatitis B serologic tests. If positive results are not indicative of active or chronic infection, the subjects can enter the study at the investigator's discretion
- Females of childbearing potential who are sexually active with a non-sterilized male partner must use a highly effective method of contraception prior to the first dose of investigational product, and must agree to continue using such precautions for 6 months after the final dose of investigational product; cessation of contraception after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. They must also refrain from egg cell donation for 6 months after the final dose of investigational product;
- Females of childbearing potential are defined as those who are not surgically sterile (ie, bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or postmenopausal (defined as 12 months with no menses without an alternative medical cause);
- A highly effective method of contraception is defined as one that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly. The acceptable methods of contraception
- Non-sterilized males who are sexually active with a female partner of childbearing potential must use a highly effective method of contraception from Days 1 through 90 post last dose. In addition, they must refrain from sperm donation for 90 days after the final dose of investigational product
- LVEF ≥50% for patients enrolling in the HER2 directed therapy arm
- Willing to attempt a baseline tumor biopsy procedure
Who cannot join
- CNS complications for whom urgent neurosurgical intervention is indicated (e.g., resection, shunt placement)
- Known leptomeningeal metastases not amenable to radiotherapy. Patients receiving radiotherapy for leptomeningeal metastases are eligible
- Received any prior monoclonal antibody against CTLA-4, programmed cell death 1 (PD1) or programmed cell death 1 ligand 1 (PD-L1)
- Subjects with a history of hypersensitivity to compounds of similar biologic composition to tremelimumab or any constituent of the product
- Subjects with a history of hypersensitivity to compounds of similar biologic composition to durvalumab or any constituent of the product;
- Patients unable to obtain MRI for any reason (e.g., due to pacemaker, ferromagnetic implants, claustrophobia, extreme obesity)
Show all 25Show fewer
- Concurrent enrollment in another therapeutic clinical study or receipt of an investigational product within the last 4 weeks (participation in the survival follow-up period of a study is not an exclusion criterion)
- Medical conditions (aside from newly-diagnosed brain metastases) for which the chronic use of corticosteroids or other immunosuppressive medications are indicated. Note: inhaled and topical steroids are permitted
- Use of immunosuppressive medications within 14 days before the first dose of study drug. The following are exceptions to this criterion: Intranasal, inhaled, topical steroids, or local steroid injections (e.g. intra articular injection); systemic corticosteroids at physiological doses not to exceed 10mg/day of prednisone or its equivalent; steroids as premedication for hypersensitivity reactions (e.g. CT scan premedication).
- Subjects should not be vaccinated with live attenuated vaccines within one month prior to starting tremelimumab treatment
- Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results
- Any serious uncontrolled medical disorder or active infection that would impair the subject's ability to receive investigational product, such as conditions associated with frequent diarrhea
- Active or history of autoimmune or inflammatory disorders, including inflammatory bowel disease (e.g., colitis, Crohn's), diverticulitis (with the exception of diverticulosis), irritable bowel disease, celiac disease or other serious gastrointestinal chronic conditions associated with diarrhea. Active or history of systemic lupus erythematosus or Wegener's granulomatosis, Sarcoidosis syndrome, Addison's disease, multiple sclerosis, Graves' disease, Hashimoto's thyroiditis, rheumatoid arthritis, hypophysitis, uveitis, etc. Patients without active disease in the last 5 years may be included but only after consultation with the study physician. Note: the following are exceptions to this criterion: Vitiligo or alopecia; patients with hypothyroidism (i.e. following Hashimoto syndrome) stable on hormone replacement; any chronic skin condition that does not require systemic therapy; patients with celiac disease controlled by diet alone;
- Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Frederica's Correction;
- Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, active peptic ulcer disease or gastritis, and active bleeding diatheses;
- Known history of previous clinical diagnosis of tuberculosis;
- History of allogeneic organ transplant;
- History of leptomeningeal carcinomatosis
- No active, second potentially life-threatening cancer. No history of another primary malignancy except for; malignancy treated with curative intent and no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence; adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; adequately treated carcinoma in situ without evidence of disease;
- Pregnant or breast feeding at time of consent
- Any condition that would prohibit the understanding or rendering of information and consent and compliance with the requirements of this protocol
- Known positive for HIV, chronic or active hepatitis B or C
- Patient is unable to receive IV contrast
- Neuroimaging evidence of midline shift
- Major surgical procedure, as defined by the investigator, within 28 days prior to the first dose of IP. Note: Local surgery or isolated lesions for palliative intent is acceptable.
Trial locations and contacts
1 site in 1 country.
United States1 site
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
About this study
Official title: A Pilot Study of Brain Irradiation and Tremelimumab in Metastatic Breast Cancer
The purpose of this study is to see if the combination of tremelimumab and durvalumab with brain radiation therapy can help treat this type of breast cancer that has spread to the brain.
Read the detailed description
A Simon 2-stage single-arm design (n=17) will be employed to evaluate for preliminary efficacy. A maximum of 17 subjects will be accrued to the efficacy arm. After the first 3 patients are enrolled in the efficacy arm, a 6 week enrollment hold will be conducted in order to ensure safety before additional patients are enrolled. An interim assessment will then occur after the first 9 subjects have enrolled, and the accrual to this arm will proceed only if a pre-specified futility threshold is met. Patients not requiring continuation of HER2 directed therapy, such as trastuzumab, will be enrolled in this arm.
- Conditions
- Metastatic Breast Cancer
- Being tested
- Brain radiotherapy or Stereotactic Radiosurgery, Tremelimumab, HER2 directed therapy, Durvalumab
- Keywords
- Brain Irradiation, Tremelimumab, 15-038
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Brain radiotherapy or Stereotactic RadiosurgeryRadiation
TremelimumabDrug
HER2 directed therapyDrug
DurvalumabDrug
| Study group | Role | What they receive |
|---|---|---|
| Radiation and Tremelimumab | Experimental | Subjects will get either whole brain radiation treatment (WBRT) or stereotactic radiosurgery (SRS), as per standard of care, with tremelimumab administered every 28 days. Patients, for whom concurrent HER2 directed therapy trastuzumab is indicated, as determined by the treating investigator, will be enrolled in a parallel HER2 directed therapy trastuzumab safety cohort. Protocol Expansion: Dose 1 of tremelimumab \& durvalumab (75 mg \& 1500 mg, respectively) will ideally be administered 2 days prior to initiation of brain radiotherapy (or between 5 days prior \& 3 days after initiation of radiotherapy). Subjects will get either WBRT or SRS, depending on the number \& size of their brain metastases. Following the 1st dose, tremelimumab \& duvralumab will be administered q28 days from the date of 1st tremelimumab \& durvalumab administration, plus or minus 1 week, for 4 cycles. After the 4th cycle, durvalumab will be administered alone until progression of disease or unacceptable toxicity. Receives: Radiation: Brain radiotherapy or Stereotactic Radiosurgery; Drug: Tremelimumab; Drug: HER2 directed therapy; Drug: Durvalumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival (irPFS)
will be defined as the time from the first dose of tremelimumab until death or progressive disease, as measured by irRC. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Measured: 12 week
Secondary outcomes (1)
Participants Assessed for Toxicity Using the NCI CTCAE 4.0
safety profile assessed with regular physical examination and toxicity assessment using the NCI CTCAE 4.0. Subjects will be followed with regular radiation oncology assessments as per the standard of care.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2015 (estimated)
- Study start18 Sep 2015
- Primary completion14 Jul 2021
- Study completion14 Jul 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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering 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
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- MedImmune LLC
- Responsible party
- Sponsor
- Investigators
- Shanu Modi, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02563925
- Sponsor's protocol ID
- 15-038
- Status last verified
- Jul 2020
- First submitted
- 28 Sep 2015
- Last updated
- 3 Aug 2022
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Page DB, Beal K, Linch SN, Spinelli KJ, Rodine M, Halpenny D, Modi S, Patil S, Young RJ, Kaley T, Merghoub T, Redmond D, Wong P, Barker CA, Diab A, Norton L, McArthur HL. Brain radiotherapy, tremelimumab-mediated CTLA-4-directed blockade +/- trastuzumab in patients with breast cancer brain metastases. NPJ Breast Cancer. 2022 Apr 19;8(1):50. doi: 10.1038/s41523-022-00404-2.
PubMed 35440655
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Brain Irradiation and Tremelimumab in Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT02563925
- Acronym / sponsor ID
- 15-038
- Conditions
- Metastatic Breast Cancer
- Keywords
- Brain Irradiation, Tremelimumab, 15-038
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- MedImmune LLC
- Study start
- 18 Sep 2015 (actual)
- Primary completion
- 14 Jul 2021 (actual)
- Study completion
- 14 Jul 2021 (actual)
- First posted
- 30 Sep 2015 (estimated)
- Results
- Posted 3 Aug 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 this study is to see if the combination of tremelimumab and durvalumab with brain radiation therapy can help treat this type of breast cancer that has spread to the brain.
Detailed description
A Simon 2-stage single-arm design (n=17) will be employed to evaluate for preliminary efficacy. A maximum of 17 subjects will be accrued to the efficacy arm. After the first 3 patients are enrolled in the efficacy arm, a 6 week enrollment hold will be conducted in order to ensure safety before additional patients are enrolled. An interim assessment will then occur after the first 9 subjects have enrolled, and the accrual to this arm will proceed only if a pre-specified futility threshold is met. Patients not requiring continuation of HER2 directed therapy, such as trastuzumab, will be enrolled in this arm.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Radiation and Tremelimumab | Experimental | Radiation: Brain radiotherapy or Stereotactic Radiosurgery, Drug: Tremelimumab, Drug: HER2 directed therapy, Drug: DurvalumabSubjects will get either whole brain radiation treatment (WBRT) or stereotactic radiosurgery (SRS), as per standard of care, with tremelimumab administered every 28 days. Patients, for whom concurrent HER2 directed therapy trastuzumab is indicated, as determined by the treating investigator, will be enrolled in a parallel HER2 directed therapy trastuzumab safety cohort. Protocol Expansion: Dose 1 of tremelimumab \& durvalumab (75 mg \& 1500 mg, respectively) will ideally be administered 2 days prior to initiation of brain radiotherapy (or between 5 days prior \& 3 days after initiation of radiotherapy). Subjects will get either WBRT or SRS, depending on the number \& size of their brain metastases. Following the 1st dose, tremelimumab \& duvralumab will be administered q28 days from the date of 1st tremelimumab \& durvalumab administration, plus or minus 1 week, for 4 cycles. After the 4th cycle, durvalumab will be administered alone until progression of disease or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Diagnosis of CNS metastases for whom SRS or WBRT is indicated, as determined by radiation oncologist assessment
- Age 18 and older at the time of consent
- Written informed consent and authorization obtained from the subject/HIPAA-appointed legal representative prior to performing any protocol-related procedures including screening evaluations
- ECOG performance of 0-2 with anticipated life expectancy of ≥12 weeks
- Histologically or cytologically confirmed invasive breast cancer that is HER2-positive (3+ by IHC and/or >2.0 by FISH) if concurrent HER2-directed therapy is planned;
Key exclusion criteria (25 listed)
- CNS complications for whom urgent neurosurgical intervention is indicated (e.g., resection, shunt placement)
- Known leptomeningeal metastases not amenable to radiotherapy. Patients receiving radiotherapy for leptomeningeal metastases are eligible
- Received any prior monoclonal antibody against CTLA-4, programmed cell death 1 (PD1) or programmed cell death 1 ligand 1 (PD-L1)
- Subjects with a history of hypersensitivity to compounds of similar biologic composition to tremelimumab or any constituent of the product
- Subjects with a history of hypersensitivity to compounds of similar biologic composition to durvalumab or any constituent of the product;
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 |
|---|---|---|
| Brain radiotherapy or Stereotactic Radiosurgery | Radiation | Radiation and Tremelimumab |
| Tremelimumab | Drug | Radiation and Tremelimumab |
| HER2 directed therapy | Drug | Radiation and Tremelimumab |
| Durvalumab | Drug | Radiation and Tremelimumab |
Primary outcome
Progression Free Survival (irPFS)
Time frame: 12 week
will be defined as the time from the first dose of tremelimumab until death or progressive disease, as measured by irRC. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
1 secondary outcome
Participants Assessed for Toxicity Using the NCI CTCAE 4.0
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35440655Page DB, Beal K, Linch SN, Spinelli KJ, Rodine M, Halpenny D, Modi S, Patil S, Young RJ, Kaley T, Merghoub T, Redmond D, Wong P, Barker CA, Diab A, Norton L, McArthur HL. Brain radiotherapy, tremelimumab-mediated CTLA-4-directed blockade +/- trastuzumab in patients with breast cancer brain metastases. NPJ Breast Cancer. 2022 Apr 19;8(1):50. doi: 10.1038/s41523-022-00404-2.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
Related trials for Metastatic Breast Cancer
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruiting
Augmented-Reality ICG Fluorescence Second-Look for Residual Nodal Disease After Axillary Dissection in Breast Cancer
Breast Cancer, Breast Neoplasms
RecruitingPhase 2
BrAin Metastasis in tripLe Negateive Breast Cancer: IvoneScimab and Trop2 ADC
Triple-Negative Breast Cancer (TNBC), Brain Metastases
RecruitingPhase 1/2
A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic or Locally Advanced Breast Cancer
Metastatic Breast Cancer
RecruitingObservational study
Collection of CSF Samples From Participants With Metastatic Triple Negative Breast Cancer (TNBC) and HER2+ Breast Cancer With no Prior History Nor Active Radiographically Detectable Brain Metastases
Breast Cancer, Breast Carcinoma
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.
Shanu Modi, MD principal investigator
Memorial Sloan Kettering Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Brain radiotherapy or Stereotactic Radiosurgery, Tremelimumab and HER2 directed therapy in people with Metastatic Breast Cancer, run by Memorial Sloan Kettering 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 22 inclusion and 25 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 3 Aug 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Aug 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?
Progression Free Survival (irPFS) (time frame: 12 week). 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 NCT02563925, which also lists 1 linked publication.
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 3 Aug 2022.