Clinical Trials /

Radioactive Drug (177Lu-DOTATATE) for the Treatment of Locally Advanced, Metastatic, or Unresectable Rare Endocrine Cancers

NCT04106843

Description:

This phase II trial studies how well 177Lu-DOTATATE works in treating patients with rare endocrine cancers that have spread from where they started to nearby tissue or lymph nodes (locally advanced), spread to other places in the body (metastatic), or cannot be removed by surgery (unresectable). Radioactive drugs, such as 177Lu-DOTATATE, may carry radiation directly to cancer cells and not harm normal cells. 177Lu-DOTATATE may help to control endocrine cancers compared to standard treatment.

Related Conditions:
  • Adrenal Gland Pheochromocytoma
  • Paraganglioma
  • Parathyroid Gland Carcinoma
  • Pituitary Gland Carcinoma
  • Thyroid Gland Medullary Carcinoma
Recruiting Status:

Withdrawn

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Radioactive Drug (177Lu-DOTATATE) for the Treatment of Locally Advanced, Metastatic, or Unresectable Rare Endocrine Cancers
  • Official Title: A Phase II Study to Evaluate the Effects of 177Lu-DOTATATE in Patients With Unresectable and Progressive Rare Metastatic Endocrine Carcinomas: Medullary Thyroid Cancer, Parathyroid Carcinoma, Pituitary Carcinoma, and Malignant Pheochromocytoma/Paraganglioma

Clinical Trial IDs

  • ORG STUDY ID: 2018-0947
  • SECONDARY ID: NCI-2019-05859
  • SECONDARY ID: 2018-0947
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT04106843

Conditions

  • Locally Advanced Adrenal Gland Pheochromocytoma
  • Locally Advanced Paraganglioma
  • Metastatic Adrenal Gland Pheochromocytoma
  • Metastatic Paraganglioma
  • Metastatic Parathyroid Gland Carcinoma
  • Pituitary Gland Carcinoma
  • Somatostatin Receptor Positive
  • Stage III Thyroid Gland Medullary Carcinoma AJCC v8
  • Stage IV Thyroid Gland Medullary Carcinoma AJCC v8
  • Stage IVA Thyroid Gland Medullary Carcinoma AJCC v8
  • Stage IVB Thyroid Gland Medullary Carcinoma AJCC v8
  • Stage IVC Thyroid Gland Medullary Carcinoma AJCC v8
  • Unresectable Adrenal Gland Pheochromocytoma
  • Unresectable Paraganglioma

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 studies how well 177Lu-DOTATATE works in treating patients with rare endocrine cancers that have spread from where they started to nearby tissue or lymph nodes (locally advanced), spread to other places in the body (metastatic), or cannot be removed by surgery (unresectable). Radioactive drugs, such as 177Lu-DOTATATE, may carry radiation directly to cancer cells and not harm normal cells. 177Lu-DOTATATE may help to control endocrine cancers compared to standard treatment.

Detailed Description

      PRIMARY OBJECTIVE:

      I. Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
      determined by Ia. Computed tomography (CT) or Ib. Magnetic resonance imaging (MRI).

      SECONDARY OBJECTIVES:

      I. To estimate progression-free survival at 1-year. II. To correlate blood pressure control
      and change/discontinuation of antihypertensive medications with tumor responses in patients
      with pheochromocytomas and paragangliomas (PHPGs).

      III. To correlate plasma metanephrines and chromogranin A with tumor responses in patients
      with PHPGs.

      IV. To correlate calcitonin, carcinoembryonic antigen, and chromogranin A with tumor
      responses in patients with medullary thyroid carcinoma (MTCs).

      V. To correlate pituitary hormones (depending on particular tumor, e.g. prolactin for
      prolactinomas, insulin-like growth factor (IGF-1) for acromegaly, adrenocorticotropic hormone
      (ACTH) and 24-hour urine free cortisol for Cushing disease, and chromogranin A with tumor
      responses in patients with functional pituitary carcinomas).

      VI. To correlate calcium, intact parathyroid hormone (iPTH), and chromogranin A with tumor
      responses in patients with parathyroid carcinoma.

      VII. Toxicity assessment by the Common Terminology Criteria for Adverse Events version 5.0
      (CTCAE 5.0).

      VIII. To correlate tumor responses with tumor uptake score in somatostatin receptor
      scintigraphy, overall prognosis and responsiveness to lutetium Lu 177 dotatate
      (177Lu-DOTATATE).

      IX. To determine the percentage of tumors that demonstrate uptake on diagnostic
      68Gallium-DOTATATE positron emission tomography (PET)/CT that would make treatment with
      177Lu-DOTATATE feasible.

      EXPLORATORY OBJECTIVES:

      I. To evaluate pituitary function in all patients to look for possible radiation late effects
      on the pituitary gland.

      II. To estimate best biochemical response for specific tumor markers in patients with
      non-measurable disease.

      III. To correlate biochemical response in patients with non-measurable disease with RECIST
      1.1 tumor response criteria for patients with non-measurable disease.

      OUTLINE:

      Patients receive 177Lu-DOTATATE intravenously (IV) over 30 minutes every 8-16 weeks.
      Treatment continues for up to 52 weeks in the absence of disease progression or unacceptable
      toxicity.

      After completion of study treatment, patients are followed up at week 72 and then every 24
      weeks for up to 5 years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (177Lu-DOTATATE)ExperimentalPatients receive 177Lu-DOTATATE IV over 30 minutes every 8-16 weeks. Treatment continues for up to 52 weeks in the absence of disease progression or unacceptable toxicity.
  • Lutetium Lu 177 Dotatate

Eligibility Criteria

        Inclusion Criteria:

          -  Histological confirmation of PHPG, MTC, parathyroid or pituitary tumor

          -  Locally advanced or distantly metastatic disease not amenable to surgery

          -  Patients should have somatostatin receptor (SSTR)+ tumor as determined by
             68Ga-DOTATATE PET/CT imaging. A measurable SSTR+ tumor is defined as having greater
             than or equal to 10 mm in diameter with uptake higher than or equal to liver and is
             qualitatively higher and distinguishable from background activity

          -  In patients with multiple lesions (more than one) as determined by staging CT or MRI,
             the number of SSTR+ lesions should be more than or equal to the number of SSTR-
             lesions

          -  Patients enrolled in cohorts 1-4 should have measurable disease defined by RECIST 1.1

          -  Patients enrolled in cohort 5 should have non-measurable disease as defined by RECIST
             1.1

          -  Progressive disease per RECIST 1.1 as determined by the investigator within the 12
             months preceding study enrollment

          -  Radiographic assessment of all known disease sites, e.g., by computerized tomography
             (CT) scan, magnetic resonance imaging (MRI), bone scan as appropriate within 28 days
             before the first dose of (177)Lu-DOTATATE

          -  Disease specific hormonal studies to assess abnormal hormonal secretion within 28 days
             before the first dose of (177)Lu-DOTATATE. These studies may include the following:
             plasma metanephrines and catecholamines for PHPG, calcitonin and CEA for MTC,
             prolactin for malignant prolactinomas, IGF-1 for growth hormone secreting malignant
             somatotropinomas, ACTH for malignant corticotropinomas, intact parathyroid hormone for
             parathyroid carcinomas

          -  Eastern Cooperative Oncology Group (ECOG) performance status of =< 2

          -  Life expectancy of at least 6 months

          -  Absolute neutrophil count (ANC) >= 1500/mm^3 without colony stimulating factor support
             (within 4 days prior to the first dose of [177]Lu-DOTATATE)

          -  Platelets >= 100,000/mm^3 (within 4 days prior to the first dose of [177]Lu-DOTATATE)

          -  Hemoglobin >= 9 g/dL (within 4 days prior to the first dose of [177]Lu-DOTATATE)

          -  Bilirubin =< 1.5 x the upper limit of normal (ULN) (within 4 days prior to the first
             dose of [177]Lu-DOTATATE). For subjects with known Gilbert's disease, bilirubin =< 3.0
             mg/dL

          -  Serum albumin >= 2.8 g/dl (within 4 days prior to the first dose of [177]Lu-DOTATATE)

          -  Serum creatinine =< 1.5 x ULN or creatinine clearance (CrCl) >= 50 mL/min (within 4
             days prior to the first dose of [177]Lu-DOTATATE). For creatinine clearance
             estimation, the Cockcroft and Gault equation should be used

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3.0 x ULN
             (within 4 days prior to the first dose of [177]Lu-DOTATATE)

          -  Random urine protein/creatinine ratio (UPCR) =< 1 (within 4 days prior to the first
             dose of [177]Lu-DOTATATE)

          -  Serum phosphorus, calcium, magnesium and potassium >= lower limit of normal (LLN)
             (within 4 days prior to the first dose of [177]Lu-DOTATATE)

          -  Capable of understanding and complying with the protocol requirements and has signed
             the informed consent document

          -  Sexually active patients (men and women) must agree to use medically accepted barrier
             methods of contraception (e.g., male or female condom) during the course of the study
             and for 4 months after the last dose of study drug(s), even if oral contraceptives are
             also used. All subjects of reproductive potential must agree to use both a barrier
             method and a second method of birth control during the course of the study and for 6
             months after the last dose of study drug(s)

          -  Women of childbearing potential must have a negative pregnancy test at screening.
             Women of childbearing potential include women who have experienced menarche and who
             have not undergone successful surgical sterilization (hysterectomy, bilateral tubal
             ligation, or bilateral oophorectomy) or are not postmenopausal. Postmenopause is
             defined as amenorrhea >= 12 consecutive months. Note: women who have been amenorrheic
             for 12 or more months are still considered to be of childbearing potential if the
             amenorrhea is possibly due to prior chemotherapy, antiestrogens, ovarian suppression
             or any other reversible reason

        Exclusion Criteria:

          -  Received cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) or
             biologic agents (e.g., somatostatin analogues, cytokines or antibodies) within 12
             weeks, or nitrosoureas/mitomycin C within 6 weeks before the first dose of study
             treatment. For patients with acromegaly, Cushing disease, and thyroid-stimulating
             hormone (TSH) secreting pituitary carcinomas treatment with somatostatin analogues is
             allowed

          -  Prior treatment with (177)Lu-DOTATATE or other radionuclide agents (e.g. (131)I
             meta-iodobenzylguanidine, (131)I Ultratrace Iobenguane)

          -  Radiation therapy for bone metastasis within 2 weeks, any other external radiation
             therapy within 4 weeks before the first dose of study treatment. Subjects with
             clinically relevant ongoing complications from prior radiation therapy are not
             eligible

          -  Prior treatment of any small molecule kinase inhibitor (including investigational
             kinase inhibitor) within 14 days before the first dose of study treatment

          -  Receipt of any other type of investigational agent within 28 days before the first
             dose of study treatment

          -  The subject has not recovered to baseline or CTCAE =< grade 1 from toxicity due to all
             prior therapies except alopecia and other non-clinically significant adverse events
             (AEs)

          -  Prothrombin time (PT)/international normalized ratio (INR) or partial thromboplastin
             time (PTT) test >= 1.3 x the laboratory ULN within 7 days before the first dose of
             study treatment

          -  Uncontrolled, significant intercurrent or recent illness including, but not limited
             to, the following conditions:

               -  Cardiovascular disorders including

                    -  Congestive heart failure (CHF): New York Heart Association (NYHA) class III
                       (moderate) or class IV (severe) at the time of screening

                    -  Concurrent uncontrolled hypertension defined as sustained blood pressure
                       (BP) > 150 mm Hg systolic, or > 90 mm Hg diastolic despite optimal
                       antihypertensive treatment within 7 days of the first dose of study
                       treatment

               -  Any of the following within 6 months before the first dose of study treatment:

                    -  Unstable angina pectoris

                    -  Clinically-significant cardiac arrhythmias

                    -  Stroke (including transient ischemic attack (TIA), or other ischemic event)

                    -  Myocardial infarction

          -  Other clinically significant disorders such as:

               -  Active infection requiring systemic treatment within 28 days before the first
                  dose of study treatment

               -  Serious non-healing wound/ulcer/bone fracture within 28 days before the first
                  dose of study treatment

               -  History of organ transplant

               -  Concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days
                  before the first dose of study treatment; in patients with central hypothyroidism
                  due to pituitary cancer FT4 should be within normal limits, TSH is not evaluable
                  for this cohort

               -  Major surgery within 12 weeks before the first dose of study treatment. Complete
                  wound healing from major surgery must have occurred 1 month before the first dose
                  of study treatment. Minor surgery within 28 days before the first dose of study
                  treatment with complete wound healing at least 10 days before the first dose of
                  study treatment. Subjects with clinically relevant ongoing complications from
                  prior surgery are not eligible

          -  Pregnant or breastfeeding

          -  A previously identified allergy or hypersensitivity to components of the study
             treatment formulation

          -  Unable or unwilling to abide by the study protocol or cooperate fully with the
             investigator or designee

          -  Evidence within 2 years of the start of study treatment of another malignancy that
             required systemic treatment except for cured non-melanoma skin cancer, cured in situ
             cervical carcinoma, or papillary microcarcinoma as long as there is no evidence of
             disease

          -  Any other severe acute or chronic medical or psychiatric condition or laboratory
             abnormality which, in the judgment of the investigator, would have made the patient
             inappropriate for entry into this study
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:Up to 52 weeks
Safety Issue:
Description:Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 determined by computed tomography (CT) or magnetic resonance imaging (MRI). Will be calculated as the proportion of patients with complete responses (CR), partial responses (PR), or stable disease (SD) at the CT/MRI assessment time point.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:M.D. Anderson Cancer Center

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