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

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ClinicalTrials.gov Identifier: NCT03132467
Recruitment Status : Recruiting
First Posted : April 27, 2017
Last Update Posted : November 14, 2018
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

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.

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.


Condition or disease Intervention/treatment Phase
Breast Cancer Hormone Receptor Positive, HER2 Negative Breast Cancer Drug: Tremelimumab Drug: Durvalumab Procedure: Core Breast Tumor Biopsy Early Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 13, 2017
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : June 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Durvalumab

Arm Intervention/treatment
Experimental: Tremelimumab + Durvalumab

Participants 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.

Drug: Tremelimumab
75 mg by vein on Day 1 of each cycle for 2 doses/cycles.
Other Names:
  • Ticilimumab
  • CP-675,206

Drug: Durvalumab
1500 mg by vein on Day 1 for 2 doses/cycles.
Other Name: MEDI4736

Procedure: Core Breast Tumor Biopsy
Participant have a core breast tumor biopsy before participant begins treatment, at the end of Cycle 2, and during participant's surgery.




Primary Outcome Measures :
  1. 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 ]
    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.

  2. 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 ]
    Feasibility established if at least 10 patients complete the study and have available immune data.

  3. Safety of Tremelimumab plus Durvalumab in Participants with Early Stage HR+/HER2- Breast Cancer: Adverse events recorded according to CTCAE 4.03 [ Time Frame: 12 months ]
    Adverse events recorded according to CTCAE 4.03.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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) 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03132467


Contacts
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Contact: Jennifer Litton, MD 713-792-2817 jlitton@mdanderson.org

Locations
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United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact       jlitton@mdanderson.org   
Sponsors and Collaborators
M.D. Anderson Cancer Center
AstraZeneca
Investigators
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Principal Investigator: Jennifer Litton, MD M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03132467     History of Changes
Other Study ID Numbers: 2016-0902
NCI-2018-01189 ( Registry Identifier: NCI CTRP )
First Posted: April 27, 2017    Key Record Dates
Last Update Posted: November 14, 2018
Last Verified: November 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
Breast Cancer
Hormone Receptor Positive, HER2 Negative Breast Cancer
Tremelimumab
Ticilimumab
CP-675,206
Durvalumab
MEDI4736

Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Antibodies
Antibodies, Monoclonal
Durvalumab
Ipilimumab
Tremelimumab
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological
Antineoplastic Agents