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LAnreotide in Metastatic Pheochromocytoma / PARAganglioma (LAMPARA) (LAMPARA)

Primary Purpose

Paraganglioma, Pheochromocytoma

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Lanreotide
Sponsored by
Antonio Fojo
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Paraganglioma focused on measuring advanced paraganglioma, advanced pheochromocytoma, metastatic paraganglioma, metastatic pheochromocytoma, lanreotide

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

For inclusion in the study, patients must fulfill all of the following criteria:

  1. Male or female at least 18 years of age at the time of first dosing
  2. Patients must give signed informed consent before any study-related activities are conducted.
  3. Patients in the United States must have given written authorization for the release of protected health information in compliance with HIPAA regulations; patients in other countries must provide appropriate authorization as needed by regulatory authorities in each country.
  4. Histologically or cytologically confirmed diagnosis of malignant paraganglioma or pheochromocytoma and either evidence of metastases or unresectability.
  5. 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.
  6. Measurable disease defined as that which can be measured in at least one dimension with a minimum size of 10 mm by CT scan. The patient must also have at least three baseline radiographic studies obtained in the previous twelve 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 twelve 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
  7. Confirmation of positive somatostatin receptor status (SRS) by Somatostatin Receptor Scintigraphy. Either 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 a SRS study be required. if an SRS is required, it will be performed greater than or equal to 24 hours after a previous injection of subcutaneous octreotide).
  8. Patients may not have had prior octreotide, long acting release (LAR)-octreotide, lanreotide or a therapeutic radiolabeled somatostatin analog (PRRT)
  9. Eastern Cooperative Oncology Group (ECOG) 0-2.
  10. Life expectancy of greater than 12 weeks.
  11. Patients must have prothrombin time (PT)/international normalized ratio (INR)/partial thromboplastin time (PTT) within 2 x the upper limit
  12. Patients may have had prior radiation therapy. A minimum of 42 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.
  13. Previous surgery: Previous major surgery is permitted provided that it was performed at least 28 days prior to patient registration.
  14. Laboratory requirements [parameter limits]: Absolute granulocyte count (AGC) greater than 1.5 x 109/L; platelet count greater than100 x 109/L; serum bilirubin less than 1.5 x upper limit of normal (ULN); serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 2.5 x ULN; serum amylase less than1.5 x ULN; serum lipase less than 1.5 x ULN; serum calcium less than 3 mmol/L; serum creatinine less than 1.5 x ULN
  15. 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); local methods such as condoms or sponges/vaginal tablets are only to be used as an additional form of contraception.
  16. 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).
  17. 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:

  1. 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
  2. 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
  3. Treatment with sunitinib, radiotherapy, a radiolabelled specific somatostatin receptor (SSTR) analog, and/or tumor debulking less than 14 days prior to the start of study therapy (lanreotide). Treatment with metaiodobenzylguanidine (MIBG) therapy less than 90 days prior to the start of study therapy (lanreotide).
  4. History of hepatic arterial embolization or hepatic arterial chemoembolization less than 28 days prior to the start of study therapy (lanreotide). Measurable disease shall exist outside of treated lesions for eligibility.
  5. History of hepatic selective internal radiation therapy (e.g. Sir-spheres) less than 90 days prior the start of study therapy (lanreotide). Measurable disease shall exist outside the liver for eligibility.
  6. 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) and/or hypertension (defined as inability to maintain blood pressure levels below systolic 140 mm Hg and/or diastolic 90 mm Hg on at least three antihypertensive medications, within last 28 days prior to screening).
  7. Renal impairment (glomerular filtration rate less than 30 ml/min/1.73m2) and/or liver impairment (serum total bilirubin greater than 1.5 x ULN, or greater than 2.5 x ULN if liver metastases)
  8. 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).
  9. Any malignancies except:

    • Basal cell carcinoma of the skin
    • 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 phaeochromocytomas and paragangliomas (PPGL) malignancy)
  10. Any serious medical condition that could jeopardize the safety of the patient and/or the efficacy assessments of the study

Sites / Locations

  • Columbia University Irving Medical CenterRecruiting
  • Cleveland ClinicRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

lanreotide arm

Arm Description

Patients with a histopathologically confirmed diagnosis of malignant paraganglioma or pheochromocytoma and either evidence of metastases or unresectability who meet the inclusion/exclusion criteria. Approximately 40 patients will be enrolled.

Outcomes

Primary Outcome Measures

Rate of tumor growth
Efficacy will be assessed by measuring the tumor growth rate while a patient is enrolled on study and comparing the growth rates on lanreotide to the pre-enrollment growth rates. Tumor growth measured by a CT or MRI scan in pre-treatment, and minimum of three scans (prior to every 3rd visit, or every 12 weeks) in post-treatment.

Secondary Outcome Measures

Overall survival (OS)
The length of time from the start of treatment that subjects with the disease are still alive.
Overall Response Rate (ORR)
ORR is defined as the proportion of the subjects in the analysis population who have a complete response (CR) or partial response (PR). Responses are based on assessments per RECIST 1.1. Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in the RECIST criteria. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have change in short axis to less than 10 mm. Partial Response (PR): At least a 30% change in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Progression-free survival
PFS is defined as the time from the first day of treatment to the first documented disease progression per RECIST 1.1 criteria and the Kaplan-Meier curve. Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in the RECIST criteria.
Magnitude of change in analyte levels
Biochemical response of greater than 20% change in 24-hour urinary metanephrines, catecholamines and serum chromogranin A levels compared to baseline, sustained for >12-week-period. Evaluated every two months while enrolled on study, although levels may be obtained as frequently as the investigator desires.

Full Information

First Posted
May 9, 2019
Last Updated
October 5, 2022
Sponsor
Antonio Fojo
Collaborators
Ipsen
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1. Study Identification

Unique Protocol Identification Number
NCT03946527
Brief Title
LAnreotide in Metastatic Pheochromocytoma / PARAganglioma (LAMPARA)
Acronym
LAMPARA
Official Title
Exploratory Phase II Study of LAnreotide in Metastatic Pheochromocytoma/PARAganglioma (LAMPARA)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
June 17, 2019 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Antonio Fojo
Collaborators
Ipsen

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The objectives of this study are: To assess the efficacy of lanreotide given every 4 weeks in participants with advanced or metastatic paraganglioma/ pheochromocytoma. To assess the toxicity and safety of lanreotide in participants with advanced or metastatic paraganglioma/ pheochromocytoma. To document the effects of lanreotide on markers of biochemical activity in participants with advanced or metastatic paraganglioma/ pheochromocytoma. Primary endpoints: โ€ข Assess efficacy by estimating the tumor growth rate while a patient is enrolled on study and comparing the growth rates on lanreotide to the pre-enrolment growth rate. Secondary endpoints include measurement of: Overall survival (OS) Progression-free survival (PFS) Overall response rate (ORR) according to RECIST defined as partial response (PR) + complete response (CR) Magnitude of reduction in levels of 24-hour urinary metanephrines, catecholamines and magnitude of reduction in serum chromogranin A, evaluated every two months while enrolled on study.
Detailed Description
Lanreotide is FDA approved for certain kinds of neuroendocrine tumors. This study seeks to determine if lanreotide is beneficial for patients with paraganglioma/ pheochromocytoma. Given the rarity of pheochromocytoma/paraganglioma that precludes the conduct of a randomized clinical trial in a timely manner, a novel method for assessing efficacy is being proposed. Efficacy will be assessed by estimating the tumor growth rate while a patient is enrolled on study and comparing the growth rates on lanreotide to the pre-enrollment growth rates. The method of analysis that will be used has been previously described. For this assessment a minimum of three tumor measurements will be required.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Paraganglioma, Pheochromocytoma
Keywords
advanced paraganglioma, advanced pheochromocytoma, metastatic paraganglioma, metastatic pheochromocytoma, lanreotide

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
lanreotide arm
Arm Type
Experimental
Arm Description
Patients with a histopathologically confirmed diagnosis of malignant paraganglioma or pheochromocytoma and either evidence of metastases or unresectability who meet the inclusion/exclusion criteria. Approximately 40 patients will be enrolled.
Intervention Type
Drug
Intervention Name(s)
Lanreotide
Other Intervention Name(s)
Somatuline Depot
Intervention Description
Participants will receive lanreotide 120 mg deep subcutaneous injection every 4 weeks (ยฑ7 days) for 52 weeks, followed by an extension phase in which all patients will continue to receive lanreotide 120 mg injection every 4 weeks (ยฑ7 days) if there is no evidence of disease progression.
Primary Outcome Measure Information:
Title
Rate of tumor growth
Description
Efficacy will be assessed by measuring the tumor growth rate while a patient is enrolled on study and comparing the growth rates on lanreotide to the pre-enrollment growth rates. Tumor growth measured by a CT or MRI scan in pre-treatment, and minimum of three scans (prior to every 3rd visit, or every 12 weeks) in post-treatment.
Time Frame
minimum of 32 weeks, up to 48 weeks
Secondary Outcome Measure Information:
Title
Overall survival (OS)
Description
The length of time from the start of treatment that subjects with the disease are still alive.
Time Frame
Observed for 48 weeks (start of treatment to end of treatment).
Title
Overall Response Rate (ORR)
Description
ORR is defined as the proportion of the subjects in the analysis population who have a complete response (CR) or partial response (PR). Responses are based on assessments per RECIST 1.1. Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in the RECIST criteria. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have change in short axis to less than 10 mm. Partial Response (PR): At least a 30% change in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time Frame
Minimum of 8 weeks, up to 48 weeks.
Title
Progression-free survival
Description
PFS is defined as the time from the first day of treatment to the first documented disease progression per RECIST 1.1 criteria and the Kaplan-Meier curve. Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in the RECIST criteria.
Time Frame
Up to 48 weeks.
Title
Magnitude of change in analyte levels
Description
Biochemical response of greater than 20% change in 24-hour urinary metanephrines, catecholamines and serum chromogranin A levels compared to baseline, sustained for >12-week-period. Evaluated every two months while enrolled on study, although levels may be obtained as frequently as the investigator desires.
Time Frame
Minimum of 16 weeks, up to 48 weeks.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: For inclusion in the study, patients must fulfill all of 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 HIPAA regulations; patients in other countries must provide appropriate authorization as needed by regulatory authorities in each country. Histologically or cytologically confirmed diagnosis of malignant paraganglioma or pheochromocytoma and either evidence of metastases or unresectability. 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. Measurable disease defined as that which can be measured in at least one dimension with a minimum size of 10 mm by CT scan. The patient must also have at least three baseline radiographic studies obtained in the previous twelve 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 twelve 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 (SRS) by Somatostatin Receptor Scintigraphy. Either 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 a SRS study be required. if an SRS is required, it will be performed greater than or equal to 24 hours after a previous injection of subcutaneous octreotide). Patients may not have had prior octreotide, long acting release (LAR)-octreotide, lanreotide or a therapeutic radiolabeled somatostatin analog (PRRT) Eastern Cooperative Oncology Group (ECOG) 0-2. Life expectancy of greater than 12 weeks. Patients must have prothrombin time (PT)/international normalized ratio (INR)/partial thromboplastin time (PTT) within 2 x the upper limit Patients may have had prior radiation therapy. A minimum of 42 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. Previous surgery: Previous major surgery is permitted provided that it was performed at least 28 days prior to patient registration. Laboratory requirements [parameter limits]: Absolute granulocyte count (AGC) greater than 1.5 x 109/L; platelet count greater than100 x 109/L; serum bilirubin less than 1.5 x upper limit of normal (ULN); serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 2.5 x ULN; serum amylase less than1.5 x ULN; serum lipase less than 1.5 x ULN; serum calcium less than 3 mmol/L; serum creatinine less than 1.5 x ULN 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); 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). 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 radiolabelled specific somatostatin receptor (SSTR) analog, and/or tumor debulking less than 14 days prior to the start of study therapy (lanreotide). Treatment with metaiodobenzylguanidine (MIBG) therapy less than 90 days prior to the start of study therapy (lanreotide). History of hepatic arterial embolization or hepatic arterial chemoembolization less than 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 (e.g. Sir-spheres) less than 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) and/or hypertension (defined as inability to maintain blood pressure levels below systolic 140 mm Hg and/or diastolic 90 mm Hg on at least three antihypertensive medications, within last 28 days prior to screening). Renal impairment (glomerular filtration rate less than 30 ml/min/1.73m2) and/or liver impairment (serum total bilirubin greater than 1.5 x ULN, or greater than 2.5 x ULN if liver metastases) 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). Any malignancies except: Basal cell carcinoma of the skin 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 phaeochromocytomas and paragangliomas (PPGL) malignancy) Any serious medical condition that could jeopardize the safety of the patient and/or the efficacy assessments of the study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Research Nurse Navigator
Phone
212-342-5162
Email
cancerclinicaltrials@cumc.columbia.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Antonio Fojo, MD, PhD
Phone
212-305-9422
Email
atf2116@cumc.columbia.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Antonio Fojo, MD, PhD
Organizational Affiliation
Columbia University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Columbia University Irving Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Antonio Fojo, MD, PhD
Phone
212-305-9422
Email
atf2116@cumc.columbia.edu
First Name & Middle Initial & Last Name & Degree
Antonio Fojo, MD, PhD
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bahar Laderian, MD
Phone
216-904-0811
Email
laderib@ccf.org
First Name & Middle Initial & Last Name & Degree
Bahar Laderian, MD

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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LAnreotide in Metastatic Pheochromocytoma / PARAganglioma (LAMPARA)

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