Clinical Trials /

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

NCT04529044

Description:

This phase II trial investigates how well 177Lu-DOTATATE works in treating patients with breast cancer that is stage IV or has come back (recurrent). 177Lu-DOTATATE may shrink or destroy the tumor or circulating breast cancer stem cells if they show evidence of the SSTR2. 177Lu-DOTATATE is a targeted therapy that uses DOTATATE, linked to a radioactive agent called 177Lu. DOTATATE attaches to tumor cells with SSTR2 and delivers 177Lu to kill them. Giving 177Lu-DOTATATE may help decrease the number and size of tumors and the number of circulating cancer stem cells in patient's blood for the treatment of patients with breast cancer positive for SSTR2.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 177Lu-DOTATATE for the Treatment of Stage IV or Recurrent Breast Cancer
  • Official Title: A Phase II Pilot Study of (Lutetium (177Lu)-DOTATATE in Patients With Metastatic Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: STUDY00019489
  • SECONDARY ID: NCI-2020-04795
  • SECONDARY ID: STUDY00019489
  • NCT ID: NCT04529044

Conditions

  • Anatomic Stage IV Breast Cancer AJCC v8
  • Metastatic Breast Carcinoma
  • Prognostic Stage IV Breast Cancer AJCC v8
  • Recurrent Breast Carcinoma

Interventions

DrugSynonymsArms
Lutetium Lu 177 Dotatate177 Lu-DOTA-TATE, 177 Lu-DOTA-Tyr3-Octreotate, 177Lu-DOTA0-Tyr3-Octreotate, Lutathera, Lutetium Lu 177 DOTA(0)-Tyr(3)-Octreotate, Lutetium Lu 177-DOTA-Tyr3-Octreotate, lutetium Lu 177-DOTATATE, Lutetium Oxodotreotide Lu-177Treatment (177Lu-DOTATATE)

Purpose

This phase II trial investigates how well 177Lu-DOTATATE works in treating patients with breast cancer that is stage IV or has come back (recurrent). 177Lu-DOTATATE may shrink or destroy the tumor or circulating breast cancer stem cells if they show evidence of the SSTR2. 177Lu-DOTATATE is a targeted therapy that uses DOTATATE, linked to a radioactive agent called 177Lu. DOTATATE attaches to tumor cells with SSTR2 and delivers 177Lu to kill them. Giving 177Lu-DOTATATE may help decrease the number and size of tumors and the number of circulating cancer stem cells in patient's blood for the treatment of patients with breast cancer positive for SSTR2.

Detailed Description

      PRIMARY OBJECTIVE:

      I. Assess objective response in study participants receiving lutetium Lu 177
      tetra-azacyclododecanetetra-acetic acid (dota) tyr3-octreotate (tate) (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 progression-free
      survival.

      EXPLORATORY OBJECTIVES:

      I. Evaluate changes in the number of circulating SSTR2+ breast cancer cells (including cancer
      stem cell sub-populations) following 177Lu-DOTATATE treatment.

      II. Assess changes in gene profile among SSTR2+ breast cancer cells following 177Lu-DOTATATE
      treatment.

      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.

      After completion of study treatment, patients are followed up every 3 months for up to 1
      year.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (177Lu-DOTATATE)ExperimentalPatients receive 177Lu-DOTATATE IV over 30-40 minutes during weeks 1, 8, 16, and 24 in the absence of disease progression or unacceptable toxicity.
  • Lutetium Lu 177 Dotatate

Eligibility Criteria

        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

          -  Histologically or cytologically confirmed metastatic breast carcinoma

          -  Stage IV or recurrent disease with distant metastases

          -  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)

          -  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 gallium Ga 68-HA-DOTA-TATE (68Ga DOTATATE) uptake
             with Krenning score >= 2 on positron emission tomography [PET] imaging of target
             lesions (per radiologist's assessment)

          -  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 through 6 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

          -  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
      
Maximum Eligible Age:100 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:Up to 3 months post-therapy
Safety Issue:
Description:Using the intent to treat (ITT) set and the efficacy analysis set, each ORR will be reported as a point estimate along with a 2-sided 95% exact confidence interval (CI).

Secondary Outcome Measures

Measure:Disease control rate (DCR)
Time Frame:Up to 3 months post-therapy
Safety Issue:
Description:A point estimate and 2-sided 95% CI will be provided for the DCR, defined as the proportion of participants achieving a complete response (CR), partial response (PR), or stable disease (SD) (as assessed by the investigator per Response Evaluation Criteria in Solid Tumors [RECIST] version [v]1.1).
Measure:Duration of response (DOR)
Time Frame:Up to 12 months post-therapy
Safety Issue:
Description:DOR will be plotted with cumulative incidence function curves (one curve for recurrence and one curve for non-relapse death).
Measure:Progression-free survival
Time Frame:Up to 12 months post-therapy
Safety Issue:
Description:The estimated distribution of PFS will be plotted using a Kaplan Meier curve and reported with median survival and a 95% CI.
Measure:Incidence of adverse events (AEs)
Time Frame:Up to 3 months post-therapy
Safety Issue:
Description:The severity of the AE will be assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Study drug-related AEs are those assessed by investigator as definitely or probably related. Using the safety analysis set, the incidence of treatment emergent adverse events (TEAEs) and non-treatment-related AEs will be determined for study participants who receive at least one dose of lutetium Lu 177 dotatate (177Lu- DOTATATE). The point estimate and 95% CI will be reported for overall toxicities as well as for each major organ category.
Measure:Duration of stable disease
Time Frame:Up to 12 months post-therapy
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:OHSU Knight Cancer Institute

Last Updated

August 24, 2020