177Lu-DOTATATE for the Treatment of Stage IV or Recurrent Breast Cancer

PRIMARY OBJECTIVE:

I. Assess objective response in study participants receiving lutetium Lu 177 dotatate (177Lu-DOTATATE) therapy.

SECONDARY OBJECTIVES:

I. Assess the rate of disease control following 177Lu-DOTATATE therapy. II. Evaluate duration of treatment response to 177Lu-DOTATATE. III. Assess progression-free survival (PFS). IV. Assess safety and tolerability of the 177Lu-DOTATATE therapy. V. Evaluate over time the requirements for stable disease.

OUTLINE:

Patients receive 177Lu-DOTATATE intravenously (IV) over 30-40 minutes during weeks 1, 8, 16, and 24 in the absence of disease progression or unacceptable toxicity. Patients also receive gallium (Ga) 68-DOTATATE and undergo positron emission tomography/computed tomography (PET/CT) during screening, biopsy as clinically-indicated as well as CT and/or magnetic resonance imaging (MRI) and collection of blood samples throughout the study.

After completion of study treatment, patients are followed up every 3 months for up to 5 years.

Inclusion criteria

• Life expectancy of > 6 months, as determined by the investigator
• Ability to understand and the willingness to sign a written informed consent document
• Patients aged >= 18-100 years old at time of informed consent
• Histologically or cytologically confirmed metastatic breast carcinoma
• Stage IV or recurrent disease with distant metastases
• Female and male patients with breast cancer will be included in the study
• Participants must have experienced disease progression after at least two lines of standard treatment modalities and/or one prior line of cytotoxic chemotherapy (not just endocrine therapy). Specifically, patients must have received or declined the following therapies: a) Hormone receptor positive (HR+)/HER2: endocrine therapy and CDK4/6 inhibitor (i); b) HER2+: trastuzumab, pertuzumab, T-DM1 and tucatinib; c) Triple negative breast cancer (TNBC): chemotherapy, immunotherapy (in PD-L1+ tumors). Patients can be consented if they are foregoing treatments known to confer survival advantage
• Participants must have at least one measurable site of disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v1).1 that is amendable to biopsy
• Confirmed presence of SSTR based on > 50% of lesions with DOTATATE uptake of 68Ga DOTATATE equivalent to the liver
• Participants must have fully recovered from the acute toxic effects of all prior treatment to grade 1 or less, except alopecia and =< grade 2 neuropathy which are allowed
• Participant must have Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Participant must consent to undergo a pre-treatment screening biopsy for enrollment
• Hemoglobin >= 8.0 g/dL with no blood transfusion in the past 28 days (measured within 28 days prior to administration of study treatment)
• Absolute neutrophil count (ANC) >= 2.0 x 10^9/L (measured within 28 days prior to administration of study treatment)
• Platelet count >= 75 x 10^9/L (measured within 28 days prior to administration of study treatment)
• Total bilirubin =< 3 x institutional upper limit of normal (ULN) (measured within 28 days prior to administration of study treatment)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x institutional upper limit of normal (unless liver metastases are present in which case they must be =< 5 x ULN) (measured within 28 days prior to administration of study treatment)
• Serum albumin >= 3.0 g/L, unless prothrombin time or international normalized ratio (INR) value is within the normal range (measured within 28 days prior to administration of study treatment)
• Participants must have serum creatinine =< 1.7 mg/dL, or creatinine clearance estimated of >= 51 mL/min using the Cockcroft-Gault equation or based on a 24 hour urine test (measured within 28 days prior to administration of study treatment)
• Female participants of childbearing potential (FOCBP) must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• FOCBP agree to use a highly-effective method of contraception starting with the first dose of study therapy up to 7 months after the last dose of study therapy

• FOCBP are those who are not proven postmenopausal. Postmenopausal is defined as:

• Amenorrheic for > 24 consecutive months following cessation of exogenous hormonal treatments
• Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the post menopausal range for women under 50 years of age
• Radiation-induced oophorectomy with last menses > 1 year ago
• Chemotherapy-induced menopause with > 1 year interval since last menses
• Surgical sterilization (bilateral oophorectomy or hysterectomy or tubal ligation)

Exclusion criteria

• Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of first dose of 177Lu- DOTATATE treatment

• Individuals in the follow-up phase of a prior investigational study may participate as long as it has been 4 weeks since last dose of the previous investigational agent or device
• Prior external beam radiation therapy to more than 25% of the bone marrow
• Other malignancy unless curatively treated with no evidence of disease for >= 5 years except: adequately treated non-melanoma skin cancer or curatively treated in situ cancer of the cervix
• Known brain metastases, unless these metastases have been treated and stabilized
• Peptide receptor radionuclide therapy at any time prior to study enrollment
• Known hypersensitivity to somatostatin analogues or any component of the 68Ga- DOTATATE or 177Lu- DOTATATE formulations
• Patients with uncontrolled infection will not be enrolled until infection is treated per provider discretion
• Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) class III or IV heart failure
• Uncontrolled diabetes mellitus as defined by a fasting blood glucose > 2x ULN
• Any patient receiving treatment with short-acting somatostatin analogs, which cannot be interrupted for both 24 hours before and after the administration of 177Lu, or any patient receiving treatment with long-acting release somatostatin analogs that cannot be interrupted for at least 4 weeks before the administration of 177Lu- DOTATATE
• Any surgery or radiofrequency ablation within 12 weeks prior to enrollment in the study; or prior radioembolization; chemoembolization; or external beam radiation therapy (EBRT) to > 25% of bone marrow, at any time
• Any chemotherapy or targeted therapy within 4 weeks prior to enrollment in the study
• Current spontaneous urinary incontinence making impossible the safe administration of the radioactive study agent
• Any psychiatric illness that prevents patient from informed consent process
• Any concurrent condition that, in the Investigator's opinion, would jeopardize the safety of the patient or compliance with the protocol
• Participant is pregnant or breastfeeding, or expecting to conceive within the projected duration of the trial, starting with the screening visit through 6 months after the last dose of trial treatment