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Lu-177-DOTATATE (Lutathera) in Therapy of Inoperable Pheochromocytoma/ Paraganglioma

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ClinicalTrials.gov Identifier: NCT03206060
Recruitment Status : Recruiting
First Posted : July 2, 2017
Last Update Posted : May 13, 2019
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:

Background:

Pheochromocytoma and paraganglioma are rare tumors. They usually form inside and near the adrenal gland or in the neck region. Not all these tumors can be removed with surgery, and there are no good treatments if the disease has spread. Researchers think a new drug may be able to help.

Objective:

To learn the safety and tolerability of Lu-177-DOTATATE. Also, to see if it improves the length of time it takes for the cancer to return.

Eligibility:

Adults who have an inoperable tumor of the study cancer that can be detected with Ga-68-DOTATATE PET/CT imaging

Design:

Participants will be screened with a medical history, physical exam, and blood tests.

Eligible participants will be admitted to the NIH Clinical Center.

Participants will get the study drug in an intravenous infusion. They will get 4 doses, given about 8 weeks apart.

Between 4 and 24 hours after each study drug dose, participants will have scans taken. They will lie on their back on a scanner table.

Participants will have vital signs taken. They will give blood and urine samples.

During the study, participants will have other scans taken. Some scans will use a radioactive tracer.

Participants will complete quality of life questionnaires.

Participants will be contacted by phone 1-3 days after they leave the Clinical Center. They will then be followed every 3 to 6 months for 3 years or until their disease gets worse.


Condition or disease Intervention/treatment Phase
Pheochromocytoma Paraganglioma Neuroendocrine Tumors Neuroendocrine Neoplasms Drug: Lu-177-DOTATATE Drug: Ga-68-DOTATATE Drug: F-18-FDG Drug: Amino Acid solution Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Lu-177-DOTATATE (Lutathera) in Therapy of Inoperable Pheochromocytoma/ Paraganglioma
Actual Study Start Date : October 10, 2017
Estimated Primary Completion Date : January 1, 2022
Estimated Study Completion Date : January 1, 2024


Arm Intervention/treatment
Experimental: 1/Lu-177-DOTATATE
Lu-177-DOTATATE is administered IV every 8 (+/- 2) weeks, for a total of 4 administrations. A Ga-68-DOTATATE PET and F-18-FDG-PET, as well as CT/ MRI for RECIST monitoring, will be obtained post 2 administrations and post 4 administrations. Concomitant administration of an IV infusion of an amino acid (AA solution will also be done for renal protection. Concomitant administration of an IV infusion of an amino acid (AA) solution will also be done for renal protection.
Drug: Lu-177-DOTATATE
Lu-177-DOTATATE IV at weeks 1, 8, 16 and 24

Drug: Ga-68-DOTATATE
Ga-68-DOTATATE PET/CT at weeks 15 and 31, every 24 weeks during 3 years follow up period

Drug: F-18-FDG
F-18-FDG PET/CT at weeks 15 and 31, every 24 weeks during 3 years follow up period

Drug: Amino Acid solution
AA solution will be administered 60 minutes prior to each Lu-177- DOTATATE infusion.




Primary Outcome Measures :
  1. progression-free survival [ Time Frame: 6 months ]
    Median amount of time subject survives without disease progression after treatment


Secondary Outcome Measures :
  1. safety and tolerability profile [ Time Frame: 30 days after the last dose study drug ]
    List of adverse event frequency

  2. Determine ability to decrease anti-hypertensive medication [ Time Frame: 3 years ]
    Proportion of patients using decreased amount of antihypertensivemedication

  3. Evaluate Quality of Life [ Time Frame: 3 years ]
    Proportion of patients with increased Quality of Life (QoL)

  4. Determine changes in plasma biochemical markers [ Time Frame: 3 years ]
    changes in plasma biochemical markers

  5. Time to tumor progression [ Time Frame: at disease progression ]
    Median amount of time subject survives without disease progression after treatment

  6. Objective response rate [ Time Frame: at disease progression ]
    Proportion of patients whose tumors shrunk after therapy

  7. Overall survival [ Time Frame: at death ]
    Median amount of time subject survives after therapy



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
Criteria
  • INCLUSION CRITERIA:

    1. Surgically inoperable patients with clinical diagnosis of PHEO/PGL who also have demonstrated disease histologically consistent with pheochromocytoma or paraganglioma (preferably confirmed by research site pathology review if initial pathology was done outside of research site, but not mandatory)
    2. Progressive disease by RECIST with or without symptomswithin the last 12 months Untreated patients with existing histologic diagnoses are eligible if progression can be demonstrated.
    3. PHEO/PGL that is associated with the SDHx mutations or is not associated with any known susceptibility genetic mutations for PHEO/PGL (a.k.a. apparent sporadic ), based on documented genetic testing results obtained prior to study enrollment. PHEO/PGL that is associated with non-SDHx mutations such as VHL, NF1, and RET will not be eligible for this study.
    4. Patient is or will be enrolled on protocol 00-CH-0093, Diagnosis, Pathophysiology, and Molecular Biology of Pheochromocytoma and Paraganglioma (NIH only).
    5. Both metastatic and inoperable primary-only patients are eligible
    6. Must have presence of SSTR+ disease as documented by positive Ga-68-DOTATATE PET scan within 12 weeks of anticipated treatment

      6.1 Positivity of Ga-68-DOTATATE PET scan defined as having at least one lesion that is greater than or equal to 10 mm in diameter with uptake that is higher than or equal to liver and is qualitatively higher and distinguishable from background activity.

      6.2 Measurable disease as defined by RECIST 1.1 OR patients with bone-only disease (i.e. no RECIST-measurable lesion) will also be eligible as long as the Ga-68-DOTATATE PET scan is positive

    7. Age greater than or equal to 18
    8. Karnofsky Performance Score greater than or equal to 60 or ECOG Performance Status of 2 or better
    9. Able to understand and willings to sign informed consent
    10. Ability and willingness to obtain all required scans per study schedule.
    11. Negative serum pregnancy test for women of child bearing potential or NOTE: A female is not of childbearing potential if a prior history of hysterectomy with bilateral oophorectomy or other procedure has render the patient surgically sterile, or >2 years since last menstruation.
    12. Female patients of childbearing potential and male patients who are not surgically sterile or with female partners of childbearing potential must agree to use effective, non-hormonal means of contraception (intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal gel) prior to study entry, for the duration of study participation and for 6 months (10 half-lives of Lu-177) after the last dose of Lu-177- DOTATATE
    13. Must have outside endocrinologist/medical oncologist who can follow the patient after receiving PRRT (NIH only requirement)
    14. Patients with secreting tumors must be receiving adequate pharmacologic catecholamine blockade as determined by the treating physician
    15. Ineligible, unable to or unwilling to receive standard first line therapy for PHEO/PGL

EXCLUSION CRITERIA:

  1. Creatinine clearance <50 mL/min calculated by the MDRD method, eventually confirmed by measured creatinine clearance (or measured glomerular filtration rate (GFR) using plasma clearance methods.
  2. Serum albumin less than or equal to 3.0 g/dL unless prothrombin time is within the normal range.
  3. Liver dysfunction as evidenced by Child s Class C Liver Disease or worse Alternatively, AST or ALT > 2.5 times institutional upper limit of normal (ULN) unless liver metastases are present, in which case up to 5 times ULN would be allowed
  4. Hb < 8.0 g/dL; WBC < 2.0 x 10^9/L (or Absolute Neutrophil Count < 1000); Platelets < 100 x 10^9/L
  5. In patients with symptoms of congestive heart failure, New York Heart Association (NYHA) classification of grade III or IV
  6. Pregnancy or lactation
  7. Prior anti-tumoral radionuclide therapy with unsealed sources. Prior therapy with sealed radioactive sources such as brachytherapy will be allowed.
  8. Prior local radiation therapy would be allowed as long as there is at least one non-irradiated index lesions.
  9. Known brain metastases, unless these metastases have been treated and stabilized for at least 24 weeks, prior to enrollment in the study. Patients with a history of brain metastases must have a head CT or MRI scan with contrast to document stable disease for at least 24 weeks prior to enrolment in the study.
  10. Other known co-existing malignancies except non-melanoma skin cancer and carcinoma in situ of the uterine cervix, unless definitively treated and proven no evidence of recurrence for 5 years.
  11. Patients who participated in any therapeutic clinical study with an investigational agent within the last 30 days.
  12. Patients may be on somatostatin analogue therapy (e.g. but not only limited to sandostatin or lanreotide therapy). However, therapy with somatostatin analogues should not be initiated or altered within 3 months of study enrolment. Patients on short term octreotide may have dose held for 24 hours prior to Lu-177-DOTATATE therapy. Those on long acting octreotide therapy will receive treatment at 1 to 5 days prior to their next cold octreotide dose, in order to prevent competition for the receptor.
  13. Patient weight > 400 lbs (table limit for PET scanner) or per local institutional standard for non-NIH sites.
  14. Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, hypertension (>180/110), arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  15. Inability to tolerate at least one modality of diagnostic anatomic imaging, such as CT or MRI

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): NCT03206060


Contacts
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Contact: Joy Zou, R.N. (240) 760-6153 zoujh@mail.nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    888-624-1937      
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Frank I Lin, M.D. National Cancer Institute (NCI)

Additional Information:
Publications:
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT03206060     History of Changes
Other Study ID Numbers: 170087
17-C-0087
First Posted: July 2, 2017    Key Record Dates
Last Update Posted: May 13, 2019
Last Verified: May 6, 2019

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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 National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Hypertension
Catecholamine
Familial Syndromes
Somatostatin Receptors
Ionizing Radiation

Additional relevant MeSH terms:
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Neuroendocrine Tumors
Carotid Body Tumor
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Paraganglioma, Extra-Adrenal
Pheochromocytoma
Paraganglioma
Pharmaceutical Solutions
Fluorodeoxyglucose F18
Radiopharmaceuticals
Molecular Mechanisms of Pharmacological Action