Brain Irradiation and Tremelimumab in Metastatic Breast Cancer

NCT02563925 | Completed Results

• 1 other identifier: 15-038
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Metastatic Breast Cancer

Keywords

Brain Irradiation; Tremelimumab; 15-038

Outcome Measures

Primary Outcomes (1)

• 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

  12 week

Secondary Outcomes (1)

• Participants Assessed for Toxicity Using the NCI CTCAE 4.0

  1 year

Study Arms (1)

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.

Radiation: Brain radiotherapy or Stereotactic Radiosurgery; Drug: Tremelimumab; Drug: HER2 directed therapy; Drug: Durvalumab

Interventions

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

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Measurable non-CNS disease, defined by RECIST1.1 criteria
• 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

You may not qualify if:

• 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)
• 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;

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• MedImmune LLC: collaborator

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Publications (1)

• 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.

  PMID: 35440655 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Radiosurgery; tremelimumab; durvalumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Dr. Shanu Modi, MD
• Organization: Memorial Sloan Kettering Cancer Center

modis@MSKCC.ORG

646-888-5243

Study Officials

• Shanu Modi, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2015
• First Posted: September 30, 2015
• Study Start: September 18, 2015
• Primary Completion: July 14, 2021
• Study Completion: July 14, 2021
• Last Updated: August 3, 2022
• Results First Posted: August 3, 2022

Record last verified: 2020-07

Locations

US (1)