Clinical Trials /

Durvalumab and Tremelimumab Before Surgery in Treating Patients With Hormone Receptor Positive, HER2 Negative Stage II-III Breast Cancer

NCT03132467

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Evaluating Anti-PD-L1 Antibody (Durvalumab) Plus Anti-CTLA-4 Antibody (Tremelimumab) in HR+/HER2- Breast Cancer
  • 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

Clinical Trial IDs

  • ORG STUDY ID: 2016-0902
  • NCT ID: NCT03132467

Conditions

  • Breast Cancer
  • Hormone Receptor Positive, HER2 Negative Breast Cancer

Interventions

DrugSynonymsArms
TremelimumabTicilimumab, CP-675,206Tremelimumab + Durvalumab
DurvalumabMEDI4736Tremelimumab + Durvalumab

Purpose

The goal of this clinical research study is to find the highest dose combination of tremelimumab and durvalumab [also called MEDI4736]) that can be given before standard of care pre-surgery chemotherapy to patients with HR+, HER2- breast cancer. Researchers also want to learn more about how certain immune cells may change in the body when they are given the drug combination. Researchers also want to find out how patients with HR+, HER2- breast cancer respond to the study drugs before they receive standard chemotherapy treatment.

Detailed Description

      Study Drug Administration:

      If you are found to be eligible to take part in this study, you will receive both study
      drugs in 2 study cycles that are each 4 weeks long. On Day 1 of each cycle, you will first
      receive tremelimumab by vein over about 1 hour. You will then be monitored for side effects
      for about 1 hour. You will then receive durvalumab by vein over about 1 hour, followed by
      another hour of monitoring for side effects.

      Length of Study:

      You will receive up to 2 cycles of the study drugs. You will no longer be able to take the
      study drug if the disease gets worse, if intolerable side effects occur, or if you are
      unable to follow study directions.

      Your participation on the study will be over after the follow-up visits.

      Study Procedures:

      Before you receive the study drugs for the first time:

        -  You will have a core breast tumor biopsy before you begin treatment to collect tissue
           to test for immune cells and other biomarkers. Biomarkers are found in the blood/tissue
           and may be related to your reaction to the study drug. To perform a core biopsy, the
           area is numbed and a sample of tissue is removed using a hollow core needle that has a
           cutting edge.

        -  If your screening blood test was performed more than 3 days before you begin receiving
           the study drugs, blood (about 14 teaspoons) will be drawn for the same testing
           performed during the screening.

      On Day 1 of Cycles 1 and 2:

        -  You will have a physical exam.

        -  Blood (about 5 tablespoons) and urine will be collected for routine tests.

        -  You will have an EKG to check your heart function (Cycle 1 only).

      At the end of Cycle 2:

        -  You will have a physical exam.

        -  Blood (about 3 tablespoons) will be drawn for routine tests and to check for immune
           cells and other biomarkers.

        -  You will have a second ultrasound of your breast.

        -  You will have a second core breast tumor biopsy to compare to the tissue taken before
           you started treatment.

      After this visit, you will then begin receiving the standard of care treatment for the
      disease (pre-surgery chemotherapy followed by surgery). During your surgery, blood and tumor
      samples will be collected to compare to the samples taken during the study. However, no
      additional tissue or blood will be collected beyond what is already collected for the
      standard purposes of the surgery.

      This is an investigational study. Tremelimumab is FDA approved to treat mesothelioma.
      Durvalumab is FDA approved to treat a certain type of bladder cancer. It is investigational
      to give these 2 drugs in combination to patients with HR+, HER2- breast cancer. The study
      doctor can describe how the study drugs are designed to work.

      Up to 15 participants will be enrolled in this study. All will take part at MD Anderson.
    

Trial Arms

NameTypeDescriptionInterventions
Tremelimumab + DurvalumabExperimentalParticipants receive Tremelimumab on Day 1 of each cycle by vein over about 1 hour, then receive Durvalumab by vein over about 1 hour. Participants receive study drugs in 2 study cycles that are each 4 weeks long. Participant have a core breast tumor biopsy before participant begins treatment, at the end of Cycle 2, and during participant's surgery.
  • Tremelimumab
  • Durvalumab

Eligibility Criteria

        Inclusion Criteria:

          1. Written informed consent and any locally-required authorization (e.g., HIPAA)
             obtained from the subject prior to performing any protocol-related procedures,
             including screening evaluations

          2. Age >/= 18 years at time of study entry

          3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          4. 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 ASCO-CAP criteria which are as follows: HER2 testing by 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

          5. Chemotherapy is planned for the patient in the neoadjuvant setting

          6. Adequate normal organ and marrow function as defined below: 1) Hemoglobin >/=9.0
             g/dL, 2) Absolute neutrophil count (ANC) >/=1.5 x 109/L (>/=1500 per mm3), 3)
             Platelet count >/=100 x 109/L (>/=100,000 per mm3), 4) 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. 5) AST (SGOT)/ALT (SGPT) </=2.5 x institutional upper limit of normal
             unless liver metastases are present, in which case it must be </=5 x ULN, 6) Serum
             creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or
             by 24-hour urine collection for determination of creatinine clearance.

          7. 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.

          8. 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.

        Exclusion Criteria:

          1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca
             staff and/or staff at the study site)

          2. Participation in another clinical study with an investigational product during the
             last 1 month prior to initiation of therapy

          3. Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an
             anti-CTLA4, including tremelimumab

          4. History of another primary malignancy except for: 1) 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, 2) Adequately treated non-melanoma
             skin cancer or lentigo maligna without evidence of disease, 3) Adequately treated
             carcinoma in situ without evidence of disease e.g., cervical cancer in situ

          5. Has received therapy for this current diagnosis of breast cancer including endocrine
             therapy or chemotherapy

          6. A single QT interval corrected for heart rate (QTc) >/= 470 ms. If an 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 Fredericia's Correction

          7. 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

          8. Active or prior documented autoimmune disease within the past 2 years. NOTE: Subjects
             with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within
             the past 2 years) are not excluded.

          9. Active or prior documented inflammatory bowel disease (e.g., Crohn's disease,
             ulcerative colitis)

         10. History of primary immunodeficiency

         11. History of allogeneic organ transplant

         12. History of hypersensitivity to durvalumab or tremelimumab or any excipient

         13. History of hypersensitivity to the combination or comparator agent (if applicable)

         14. 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

         15. Known history of previous clinical diagnosis of tuberculosis

         16. History of leptomeningeal carcinomatosis

         17. Receipt of live attenuated vaccination within 30 days prior to study entry or within
             30 days of receiving durvalumab or tremelimumab

         18. 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

         19. Any condition that, in the opinion of the investigator, would interfere with
             evaluation of study treatment or interpretation of patient safety or study results

         20. Subjects with uncontrolled seizures
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Feasibility of Enrolling Participants with Hormone Receptor Positive (HR+)/Human Epidermal Growth Factor Receptor negative (HER2-) Breast Cancer to Trial with Durvalumab Plus Tremelimumab
Time Frame:12 months
Safety Issue:
Description: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.

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Trial Keywords

  • Breast Cancer
  • Hormone Receptor Positive, HER2 Negative Breast Cancer
  • Tremelimumab
  • Ticilimumab
  • CP-675,206
  • Durvalumab
  • MEDI4736

Last Updated

May 11, 2017