RACHEL1: Radiation and CHEckpoint bLockade Trial in Patients With Metastatic Hormone Receptor Positive, HER2 Negative Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03524170
Recruitment Status : Recruiting
First Posted : May 14, 2018
Last Update Posted : August 24, 2018
EMD Serono
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

The goal of this clinical research study is to find the highest tolerable dose of M7824 (MSB0011359C) that can be given with radiation therapy to patients with estrogen and/or progesterone receptor (HR) positive, HER2-negative breast cancer that is metastatic (has spread). The safety and tolerability of MSB0011359C will also be studied.

Researchers also want to learn more about how certain immune cells may change when MSB0011359C in given in combination with radiation therapy. The effect of the study treatment combination will also be studied.

This is an investigational study. MSB0011359C is not FDA approved or commercially available. It is currently being used for research purposes only.

Radiation therapy is part of standard of care for many breast cancer patients.

The study doctor can describe how the study drug and radiation therapy are designed to work.

Up to 20 participants will be enrolled in this study. All will take part at MD Anderson.

Condition or disease Intervention/treatment Phase
Malignant Neoplasm of Breast Drug: M7824 Radiation: Radiation Therapy Phase 1

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: RACHEL1: A Phase I Radiation and CHEckpoint bLockade Trial in Patients With Metastatic Hormone Receptor Positive, HER2 Negative Breast Cancer
Actual Study Start Date : April 30, 2018
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : September 2020

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: M7824 + Radiation Therapy Drug: M7824

M7824 given at 1200 mg per infusion once every 14 days in a 28 day cycle.

Once a patient finishes the first 6 weeks of DLT evaluation and biopsy at 56 days, the monotherapy of M7824 administered at 1200 mg per infusion once every 14 days (maintenance period), if dose 0 is the maximum tolerated dose. If the MTD is 600 mg, then the maintenance dose will be 600 mg.

Other Name: MSB0011359C

Radiation: Radiation Therapy
Radiation therapy starts within 3 days after the 2nd infusion of M7824 to one of the sites of metastatic disease and delivered in 5 fractions x 4 Gy or 10 fractions x 3 Gy.
Other Names:
  • XRT
  • External beam radiation therapy

Primary Outcome Measures :
  1. Recommended phase II dose (RP2D) of M7824 and radiation therapy in patients with metastatic HR+/HER2- breast cancer determined by dose limiting toxicity (DLT) [ Time Frame: 6 weeks after first administration of M7824. ]
    RP2D defined as the highest dose level with no more than 1 patient with DLT out of 6 patients that are treated.

  2. Safety and tolerability of M7824 and radiation therapy in patients with metastatic HR+/HER2- breast cancer. [ Time Frame: Start of study drug up to 30 days after study drug stopped ]
    Safety determined by National Cancer Institute - Common Terminology Criteria for AEs (CTCAE), version 4.03.

Secondary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: Start of study drug up to 90 days after study drug stopped ]
    Progression-free survival (PFS) defined as the time from treatment until objective tumor progression or death, whichever occurs first.

  2. Overall survival (OS) [ Time Frame: Start of study drug up to 90 days after study drug stopped ]
    Overall survival (OS) defined as the time from treatment until death from any cause.

  3. Immunologic/molecular response [ Time Frame: 56 days ]
    Immunologic/molecular response defined as % change in tumor infiltrating lymphocytes (TIL) pre and post therapy to M7824 and radiation therapy in patients with HR+/HER2- metastatic breast cancer.

  4. Evaluation of the size of metastasis after treatment with anti-PD-L1/TGF-β Trap (M7824) with radiation (in-field) and non-irradiated (abscopal) sites determined by RECIST [ Time Frame: 56 days ]

Information from the National Library of Medicine

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

Inclusion Criteria:

  1. Is willing and able to provide written informed consent for the trial and has signed the appropriate written informed consent form, approved by the investigator's Institutional Review Board (IRB)/Independent Ethics Committee (IEC), prior to the performance of any trial activities.
  2. Is Age >/= 18 years at time of study entry
  3. ECOG Performance Status of 0-1
  4. Highly effective contraception for both male and female subjects if the risk of conception exists. Highly effective contraception must be used 30 days prior to first trial administration, for the duration of trial treatment, and at least for 4 months after stopping trial treatment (see Appendix 2 for further details). Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this trial, the treating physician should be informed immediately.
  5. Has confirmed HR+ and HER2 negative breast cancer with known metastatic disease. HR defined as positive if expression greater than 10% by immunohistochemistry (IHC). HER2 negative or non-amplified is 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: i. IHC 3+ based on circumferential membrane staining that is a. complete, intense ii. ISH positive based on: a. Single-probe average HER2 copy number =/>6.0 signals/cell. b. Dual-probe HER2/CEP17 ratio =/>2.0 with an average HER2 copy number =/>4.0 signals/cell c. Dual-probe HER2/CEP17 ratio =/>2.0 with an average HER2 copy number <4.0 signals/cell d. Dual-probe HER2/CEP17 ratio < 2.0 with an average HER2 copy number =/>6.0 signals/cell
  6. Has at least 2 identified sites of metastatic disease by imaging.
  7. Has received no more than 5 previous lines of chemotherapy and has received at least one line of therapy with an endocrine therapy or endocrine therapy combination.
  8. Adequate hematological function, defined by white blood cell (WBC) count =/> 3 × 10^9/L with ANC =/>1.5 × 10^9/L, lymphocyte count=/> 0.5 × 10^9/L, platelet count =/>100 × 10^9/L, and Hgb =/>9 g/dL
  9. Adequate hepatic function defined by a total bilirubin level </= 1.5 × the upper limit of normal (ULN), an AST, level </= 2.5 × ULN, and an ALT level </= 2.5 × ULN.
  10. International normalized ratio (INR) < 1.5
  11. Adequate renal function defined by an estimated creatinine clearance >30 mL/min according to the Cockcroft-Gault formula or be measure for creatinine clearance from 24 hour urine collection.
  12. Has not had major surgery within 28 days prior to starting study treatment. Central venous access surgeries and/or placements would not be considered as major surgery.
  13. Is eligible for palliative radiotherapy as determined by the treating radiation oncologist.

Exclusion Criteria:

  1. Anticancer treatment within 14 days before the start of trial treatment [e.g., cytoreductive therapy, radiotherapy (with the exception of palliative radiotherapy delivered in a normal organ-sparing technique), immune therapy, or cytokine therapy].
  2. Major surgery as determined by the investigator within 28 days before the start of trial treatment (prior diagnostic biopsy is permitted).
  3. Systemic therapy with immunosuppressive agents within 7 days before the start of treatment; or use of any investigational drug within 28 days before the start of trial treatment.
  4. Subjects with active central nervous system (CNS) metastases with significant neurological compromise or symptoms are excluded. Subjects with a history of treated CNS metastases (by surgery or radiation therapy), who show no evolving new neurological symptoms are eligible for the study.
  5. Receipt of any organ transplantation, including allogeneic stem-cell transplantation, but with the exception of transplants that do not require immunosuppression (e.g., corneal transplant, hair transplant).
  6. Significant acute or chronic infections including, among others: a. Known history of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome. b. Active HBV (HBV surface antigen positive) or HCV (HCV RNA positive). c. Subjects with known active tuberculosis (history of exposure or history of positive tuberculosis test plus presence of clinical symptoms, physical or radiographic findings).
  7. Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent: a. Subjects with type I diabetes, vitiligo, alopecia, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible b. Subjects requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses ≤ 10 mg of prednisone or equivalent per day.
  8. Clinically significant cardiovascular/ cerebrovascular disease as follows: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (New York Heart Association Classification Class > II), or serious cardiac arrhythmia.
  9. Clinically relevant diseases (for example, inflammatory bowel disease) and / or uncontrolled medical conditions, which, in the opinion of the Investigator, might impair the subject's tolerance or ability to participate in the trial.
  10. Vaccine administration within 4 weeks of M7824 administration. Vaccination with live vaccines while on trial is prohibited. Administration of inactivated vaccines is allowed (for example, inactivated influenza vaccines).
  11. Pregnancy and breast feeding

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 identifier (NCT number): NCT03524170

Contact: Jennifer Litton, MD 713-792-2817

United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
EMD Serono
Principal Investigator: Jennifer Litton, MD M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center Identifier: NCT03524170     History of Changes
Other Study ID Numbers: 2017-0499
NCI-2018-00961 ( Registry Identifier: NCI CTRP )
First Posted: May 14, 2018    Key Record Dates
Last Update Posted: August 24, 2018
Last Verified: August 2018

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:
Malignant neoplasm of breast
Metastatic HR+/HER2- breast cancer
Radiation therapy
External beam radiation therapy

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs