This study is NOT currently recruiting participants.
Number
000305-C
Sponsoring Institute
National Cancer Institute (NCI)
Recruitment Detail
Type: No longer recruiting/follow-up only Gender: Male & Female Min Age: 18 Years Max Age: N/A
Referral Letter Required
No
Population Exclusion(s)
Neonates;Fetuses;Pregnant Women;Children
Keywords
Advanced Paraganglioma; Advanced Pheochromocytoma; Metastatic Paraganglioma; Metastatic Pheochromocytoma; Lanreotide
Recruitment Keyword(s)
None
Condition(s)
Pheochromocytoma; Paraganglioma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Lanreotide; Antineoplastic Agents
Investigational Drug(s)
Lanreotide
Investigational Device(s)
Intervention(s)
Drug: Lanreotide
Supporting Site
National Cancer Institute
Pheochromocytomas and paragangliomas (PC/PG) are rare neuroendocrine tumors. These tumors do not respond well to current treatments, such as chemotherapy and radiation. Better treatments are needed.
Objective:
To see if a study drug (lanreotide) can shrink tumors in people with advanced PC/PGs that have spread or cannot be treated with surgery.
Eligibility:
People aged 18 years and older with advanced PC/PG that have spread or cannot be treated with surgery.
Design:
Participants will be screened with a physical exam and blood and urine tests will be collected. They will have tests of their heart function. Their tumors will be measured using CT or MRI scans. Their cancer diagnosis will be confirmed; in some cases, a new biopsy may be needed.
Participants will receive lanreotide as an injection under the skin in the buttocks once every 4 weeks. They will receive 13 doses over 52 weeks.
Starting with the screening visit, participants will keep a daily diary. They will record their morning blood pressure and pulse. They will also write down any drugs they take to manage their blood pressure or heart rhythm. Participants will acquire their own device for monitoring blood pressure at home.
Physical exams, blood, and urine tests will be repeated throughout the study. Imaging scans will be repeated every 8 weeks.
If the drug has been working well for the participants, they may be eligible to enter an Extension Phase of the study. They may continue receiving the lanreotide injections every 4 weeks for an additional year. Imaging scans will continue through the Extension Phase.
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INCLUSION CRITERIA: For inclusion in the study, patients must fulfill all the following criteria: -Male or female at least 18 years of age at the time of first dosing -Patients must give signed informed consent before any study-related activities are conducted. -Patients in the United States must have given written authorization for the release of protected health information in compliance with HIPPA regulations; patients in other countries must provide appropriate authorization as needed by regulatory authorities in each country. -Histological or cytological confirmation of malignant paraganglioma or pheochromocytoma with either evidence of metastases or unresectability. In the case of glomus jugulare and carotid body tumors, their clinical presentation and demonstration of avidity on a gallium DOTATATE scan are sufficient. -Evidence of recent disease progression (radiological, biochemical, symptomatic) while the patient was either not receiving any therapy or was receiving a therapy that was deemed ineffective. Note: Radiographic progression need not adhere to a RECIST definition of progression. NOTE: Paragangliomas can arise in the jugular fossa / jugular foramen of the temporal bone [glomus jugulare tumors] and in the carotid body [with acronyms that include carotid body tumor, glomus tumor, chemodectomas, and nonchromaffin tumor that are less accurate or obsolete]. They arise from glomus cells located within the outermost wall of the jugular bulb or from paraganglionic cells of the carotid body which contains neural elements originating from the neural crest ectoderm. Often considered benign as they may not present with metastases, they often present enormous clinical challenges since they can be locally very aggressive and difficult if not impossible to resect. Given their critical location such tumors are almost never biopsied. However, their unique clinical presentation together with avidity on somatostatin-receptor scintigraphy (gallium DOTATATE scan) are considered diagnostic. Furthermore., as they often grow very slowly, the magnitude of change in size may be small, but provided the pre-requisite baseline scans are available, these patients will be eligible to enroll on study. As such, patients who present with glomus jugulare or carotid body tumors will be eligible for enrollment on study based on the clinical/scintigraphic presentation without tissue confirmation. Additionally, patients with tumors secreting catecholamines in whom sites of potential biopsy are felt to present a risk, may be enrolled without a confirmatory biopsy after consultation with the Principal Investigator, provided their clinical presentation together with avidity on somatostatin-receptor scintigraphy (gallium DOTATATE scan) are considered diagnostic. -Measurable disease defined as that which can be measured in at least one dimension with a minimum size of 10 mm by an appropriate imaging study including MRI, CT scan or another appropriate imaging modality. The patient must also have at least three baseline radiographic studies obtained in the previous eighteen months with at least one scan obtained within six weeks of enrollment. If a patient being considered for enrollment on trial has not had three scans performed in the eighteen months prior to enrollment and if in the opinion of the investigator a delay of one month will not impact the clinical course, then enrollment on protocol and the start of the lanreotide therapy can be delayed by one month or longer to obtain the additional time point. If in the opinion of the investigator such a delay may have adverse consequences, then enrollment on the protocol should not be considered as an option -Confirmation of positive somatostatin receptor status by Somatostatin Receptor Scintigraphy (SRS, Octreotide/Pentetreotide scan, 68Gallium-DOTATATE scan, or CU64 Dotatate scan). Any of these studies will need to have been performed in the 6 months prior to the Screening Visit. Only if one has not been performed within the previous 6 months will an SRS study be required. -ECOG 0-2. -Life expectancy of greater than 12 weeks. -Patients must have PT/INR/PTT within 2 x the upper limit -Patients may have had prior radiation therapy. A minimum of 2 weeks days must have elapsed between the end of radiotherapy and registration onto the study. Measurable disease must exist outside of the radiation field for eligibility. Measurable disease must exist outside of the radiation field for eligibility. -Previous surgery: Previous major surgery is permitted if it was performed at least 28 days prior to patient registration. -Laboratory requirements [parameter limits]: Absolute granulocyte count (AGC) >1.5 x 10^9/L; platelet count >100 x 10^9/L; serum bilirubin <1.5 x ULN or <2.5 x ULN if liver metastases; serum AST and ALT <2.5 x ULN; serum calcium <3 mmol/L (<12 mg/dL); glomerular filtration rate >30 ml/min/1.73m^2 -If female, the patient must not be pregnant (confirmed by negative pregnancy test) and must have the following documented via verbally given history: -At least 1 year postmenopausal (natural cessation of menses), or --Surgically sterile (if by tubal ligation, surgery must have been performed more than 3 months prior to entry into the study), or --If of childbearing potential and sexually active, she must be using or agree to use an acceptable form of contraception (oral, injected, transdermal or implanted contraceptives, diaphragm, or barrier method with spermicidal and/or intrauterine device) throughout the duration of the study up until 6 months after the last dose. Local methods such as condoms or sponges/vaginal tablets are only to be used as an additional form of contraception. -If the male patient has a partner of childbearing potential and he is sexually active, he must be using or agree to use a barrier method of contraception (condom with spermicidal preferred) and agree to not donate sperm throughout the duration of the study up until 6 months after the last dose. -Be able to communicate and cooperate with the principal investigator and the staff and willing to comply with the study instructions EXCLUSION CRITERIA: A patient who meets any of the following criteria is ineligible for participation in the study: -Patient has a history of known allergy or hypersensitivity to: --Investigational drug or any components of its formulation --Lanreotide, octreotide or any other somatostatin analog -Treatment with any other investigational drug or with cytotoxic chemotherapy within 28 days prior to the start of study therapy (lanreotide) and/or at any time during the patient s participation in the study -Treatment with sunitinib, radiotherapy, a radiolabeled SSTR analog, and/or tumor debulking <14 days prior to the start of study therapy (lanreotide). Treatment with MIBG therapy <90 days prior to the start of study therapy (lanreotide). -History of hepatic arterial embolization or hepatic arterial chemoembolization <28 days prior to the start of study therapy (lanreotide). Measurable disease shall exist outside of treated lesions for eligibility. --History of hepatic selective internal radiation therapy (eg. Sir-spheres) <90 days prior the start of study therapy (lanreotide). Measurable disease shall exist outside the liver for eligibility. -Uncontrolled diabetes (defined as inability to maintain fasting blood glucose levels below 200 mg/dL despite best medical therapy, within last 28 days prior to screening) -Unstable hypertension defined as a systolic blood pressure >170 mm Hg or diastolic pressure >105 mmHg despite optimal medical management on three successive measurements at least 4 hours apart. -Renal impairment (glomerular filtration rate <30 ml/min/1.73m^2) and/or liver impairment (serum total bilirubin >1.5 x ULN, or >2.5 x ULN if liver metastases or serum AST and ALT >2.5 x ULN) -Uncontrolled cardiac disease (acute myocardial infarction, unstable angina or hospitalization for decompensation of congestive heart failure within the 28 days prior to the start of study therapy (lanreotide). -Patients may not have had prior octreotide, LAR-octreotide, lanreotide or a therapeutic radiolabeled somatostatin analog (PRRT) within the last 3 years -Any malignancies except: --Basal cell carcinoma of the skin or other non-melanoma skin malignancy that has been successfully resected --In situ carcinoma of the cervix --2 years disease-free after curative cancer treatment (completion of surgery, adjuvant chemotherapy and/or radiation, and considered no evidence of disease from non PPGL malignancy) -Any serious medical condition that could jeopardize the safety of the patient and/or the efficacy assessments of the study
For inclusion in the study, patients must fulfill all the following criteria:
-Male or female at least 18 years of age at the time of first dosing
-Patients must give signed informed consent before any study-related activities are conducted.
-Patients in the United States must have given written authorization for the release of protected health information in compliance with HIPPA regulations; patients in other countries must provide appropriate authorization as needed by regulatory authorities in each country.
-Histological or cytological confirmation of malignant paraganglioma or pheochromocytoma with either evidence of metastases or unresectability. In the case of glomus jugulare and carotid body tumors, their clinical presentation and demonstration of avidity on a gallium DOTATATE scan are sufficient.
-Evidence of recent disease progression (radiological, biochemical, symptomatic) while the patient was either not receiving any therapy or was receiving a therapy that was deemed ineffective. Note: Radiographic progression need not adhere to a RECIST definition of progression.
NOTE: Paragangliomas can arise in the jugular fossa / jugular foramen of the temporal bone [glomus jugulare tumors] and in the carotid body [with acronyms that include carotid body tumor, glomus tumor, chemodectomas, and nonchromaffin tumor that are less accurate or obsolete]. They arise from glomus cells located within the outermost wall of the jugular bulb or from paraganglionic cells of the carotid body which contains neural elements originating from the neural crest ectoderm. Often considered benign as they may not present with metastases, they often present enormous clinical challenges since they can be locally very aggressive and difficult if not impossible to resect. Given their critical location such tumors are almost never biopsied. However, their unique clinical presentation together with avidity on somatostatin-receptor scintigraphy (gallium DOTATATE scan) are considered diagnostic. Furthermore., as they often grow very slowly, the magnitude of change in size may be small, but provided the pre-requisite baseline scans are available, these patients will be eligible to enroll on study. As such, patients who present with glomus jugulare or carotid body tumors will be eligible for enrollment on study based on the clinical/scintigraphic presentation without tissue confirmation. Additionally, patients with tumors secreting catecholamines in whom sites of potential biopsy are felt to present a risk, may be enrolled without a confirmatory biopsy after consultation with the Principal Investigator, provided their clinical presentation together with avidity on somatostatin-receptor scintigraphy (gallium DOTATATE scan) are considered diagnostic.
-Measurable disease defined as that which can be measured in at least one
dimension with a minimum size of 10 mm by an appropriate imaging study including MRI, CT scan or another appropriate imaging modality. The patient must also have at least three baseline radiographic studies obtained in the previous eighteen months with at least one scan obtained within six weeks of enrollment. If a patient being considered for enrollment on trial has not had three scans performed in the eighteen months prior to enrollment and if in the opinion of the investigator a delay of one month will not impact the clinical course, then enrollment on protocol and the start of the lanreotide therapy can be delayed by one month or longer to obtain the additional time point. If in the opinion of the investigator such a delay may have adverse consequences, then enrollment on the protocol should not be considered as an option
-Confirmation of positive somatostatin receptor status by Somatostatin Receptor Scintigraphy (SRS, Octreotide/Pentetreotide scan, 68Gallium-DOTATATE scan, or CU64 Dotatate scan). Any of these studies will need to have been performed in the 6 months prior to the Screening Visit. Only if one has not been performed within the previous 6 months will an SRS study be required.
-ECOG 0-2.
-Life expectancy of greater than 12 weeks.
-Patients must have PT/INR/PTT within 2 x the upper limit
-Patients may have had prior radiation therapy. A minimum of 2 weeks days must have elapsed between the end of radiotherapy and registration onto the study. Measurable disease must exist outside of the radiation field for eligibility. Measurable disease must exist outside of the radiation field for eligibility.
-Previous surgery: Previous major surgery is permitted if it was performed at least 28 days prior to patient registration.
-Laboratory requirements [parameter limits]: Absolute granulocyte count (AGC) >1.5 x 10^9/L; platelet count >100 x 10^9/L; serum bilirubin <1.5 x ULN or <2.5 x ULN if liver metastases; serum AST and ALT <2.5 x ULN; serum calcium <3 mmol/L (<12 mg/dL); glomerular filtration rate >30 ml/min/1.73m^2
-If female, the patient must not be pregnant (confirmed by negative pregnancy test) and must have the following documented via verbally given history:
-At least 1 year postmenopausal (natural cessation of menses), or
--Surgically sterile (if by tubal ligation, surgery must have been performed more than 3 months prior to entry into the study), or
--If of childbearing potential and sexually active, she must be using or agree to use an acceptable form of contraception (oral, injected, transdermal or implanted contraceptives, diaphragm, or barrier method with spermicidal and/or intrauterine device) throughout the duration of the study up until 6 months after the last dose.
Local methods such as condoms or sponges/vaginal tablets are only to be used as an additional form of contraception.
-If the male patient has a partner of childbearing potential and he is sexually active, he must be using or agree to use a barrier method of contraception (condom with spermicidal preferred) and agree to not donate sperm throughout the duration of the study up until 6 months after the last dose.
-Be able to communicate and cooperate with the principal investigator and the staff and willing to comply with the study instructions
EXCLUSION CRITERIA:
A patient who meets any of the following criteria is ineligible for participation in the study:
-Patient has a history of known allergy or hypersensitivity to:
--Investigational drug or any components of its formulation
--Lanreotide, octreotide or any other somatostatin analog
-Treatment with any other investigational drug or with cytotoxic chemotherapy within 28 days prior to the start of study therapy (lanreotide) and/or at any time during the patient s participation in the study
-Treatment with sunitinib, radiotherapy, a radiolabeled SSTR analog, and/or tumor debulking <14 days prior to the start of study therapy (lanreotide). Treatment with MIBG therapy <90 days prior to the start of study therapy (lanreotide).
-History of hepatic arterial embolization or hepatic arterial chemoembolization <28 days prior to the start of study therapy (lanreotide). Measurable disease shall exist outside of treated lesions for eligibility.
--History of hepatic selective internal radiation therapy (eg. Sir-spheres) <90 days prior the start of study therapy (lanreotide). Measurable disease shall exist outside the liver for eligibility.
-Uncontrolled diabetes (defined as inability to maintain fasting blood glucose levels below 200 mg/dL despite best medical therapy, within last 28 days prior to screening)
-Unstable hypertension defined as a systolic blood pressure >170 mm Hg or diastolic pressure >105 mmHg despite optimal medical management on three successive measurements at least 4 hours apart.
-Renal impairment (glomerular filtration rate <30 ml/min/1.73m^2) and/or liver
impairment (serum total bilirubin >1.5 x ULN, or >2.5 x ULN if liver metastases or serum AST and ALT >2.5 x ULN)
-Uncontrolled cardiac disease (acute myocardial infarction, unstable angina or hospitalization for decompensation of congestive heart failure within the 28 days prior to the start of study therapy (lanreotide).
-Patients may not have had prior octreotide, LAR-octreotide, lanreotide or a therapeutic radiolabeled somatostatin analog (PRRT) within the last 3 years
-Any malignancies except:
--Basal cell carcinoma of the skin or other non-melanoma skin malignancy that has been successfully resected
--In situ carcinoma of the cervix
--2 years disease-free after curative cancer treatment (completion of surgery, adjuvant chemotherapy and/or radiation, and considered no evidence of disease from non PPGL malignancy)
-Any serious medical condition that could jeopardize the safety of the patient and/or the efficacy assessments of the study
Principal Investigator
Referral Contact
For more information: