Ga-68-DOTATOC -PET in the Management of Pituitary Tumours

Title: Gallium (GA) -68-DOTATOC -PET (positron emission tomography) in the management of pituitary tumours Medical product: Ga-68-DOTATOC in PET/computer tomography (CT) Route of administration: Intravenously Diseases of interest: Pituitary tumours Aim: To study the detection of pituitary tumours with Ga-68-DOTATOC -PET (Ga-PET) and to correlate the tracer expression to somatostatin receptor (sst) occurrence Study design: Prospective non-randomised case-control study with open design with GA-PET before and after pituitary surgery in patients with pituitary tumours Study population: patients with acromegaly (n=10), Cushing's' disease of pituitary origin (n=10), TSH (thyreotropin) producing tumours (TSHomas) (n=5) and non-functioning pituitary adenomas (NFPA) (n=20) Number of patients: 45 Inclusion criteria: Adult man or woman (over 18 years) and naïve, unoperated pituitary tumour with growth hormone (GH) or adrenocorticotrophic hormone (ACTH)) or TSH production or NFPA without treatment with somatostatin analogues (SSA) or dopamine agonists.

Exclusion criteria: Patient who may not attend to the protocol according to the investigators opinion. Pregnancy or lactating. Isolated prolactin producing tumours. Overproduction of gonadotropins. Carcinoids ie ectopic corticotrophin realising factor (CRF) production. Known or suspected allergy to the trial product or related products.

Controls: Adult patients with Thyroid associated ophthalmopathy (TAO) before iv steroid infusion (part of another study see this protocol)- Study variables: Tumour detection, Tracer uptake as Standardised uptake value (SUV) max (SUVmax), SUV hotspot and SUV mean in regions of interests (ROIs) Time schedule: Recruitment of patients 2015-2017. Study termination 3 years later

Study Overview

• Status: Terminated
• Conditions: Pituitary Tumours
• Intervention / Treatment: Drug: Gallium-68 DOTATOC PET

Detailed Description

Background The most common cause to pituitary insufficiency is the pituitary adenoma (PA). PA may be divided into hormone producing PAs and non-functioning PAs (NFPA). Normal pituitary tissue, as well as tissues from PAs, expresses somatostatin receptors (sst). Five subtypes of sst receptors has been characterized.

Magnetic resonance tomography (MRI) presents anatomy, while in vivo diagnostics with somatostatin receptor scintigraphy (SRS) or position emission tomography (PET) reflect the functional properties of the tissue. The SRS have earlier been evaluated for diagnostics of pituitary diseases and has low discriminative ability to differ tumor tissue from normal pituitary tissue even though some secretory tumors and NFPA are seen. The superiority of the PET in diagnostics compared to the SRS is based on higher spatial resolution and a higher tumor to background ratio. Therefore it is of large interest to study Gallium 68 DOTATOC (Ga-PET) i small tumours that exhibit sst, such as in the pituitary, where high resolution is essential to discriminate from normal tissue and to evaluated residual tumor tissue postoperatively.

Aim with the project

To evaluate Ga-PET in the management of pituitary tumors and to seek the answer to the following questions:

1. Is the method of value in primary diagnostics in PAs? Does Ga-PET contribute with more functional information than that given from an conventional MRI?
2. Is the method of value in the follow-up, the detection of residual tumor tissue, and increase the possibility to differ scar tissue from true tumor?
3. Can relapses of PA be detected earlier with Ga-PET than with conventional MRI?
4. Are some of the sub-groups easier to detect that others??
5. Can the pathological-anatomical findings and the immunochemical expression of sst be correlated to the PET findings?
6. Can the treatment with somatostatin analogues be designed from the PET investigation and the sst analysis?

Method The aim is to recruit 10 patients with acromegaly (GH-producing PA), 10 patients with Cushing's disease (ACTH-producing PA), 5 patients with TSH-producing PA (TSHoma) and 20 patients with NFPA and to do Ga-PET before and after the pituitary surgery. In the Cushing patients, the TSHomas and in NFPA Ga-PET will also be dome after 3 years postoperatively to detect recurrences. At surgery, pituitary tissue is taken to investigate hormonal expression, sst and for further molecular genetic studies. At all PET occasions blood specimens from the patients are collected for future analyses. They will be kept in a freezer.

If difficulties to separate the Ga-Pet up-take in tumors from normal pituitary tissue the tumor expression may be enhanced by a somatostatin injection before Ga-PET that suppresses normal tissue.

The pituitary PET of pituitary tumours patients will be compared with the pituitary of patients with thyroid associated tumours performing PET according to the similar protocol in Another study

Significance This study is a pilot study. Ga-PET has not been used in pituitary tumors but there is known from studies in patients with gastrointestinal neuroendocrine tumors that the pituitary is seen on GA-PET. This is a "proof of concept". It addresses some of the clinical problems in the management of pituitary tumors. If the questions addressed in this study will be answered in advantage for PET, PET may be a routine investigation and the patients may avoid invasive procedures and repeated MRI. In addition, the patients may have better information regarding cure or not. If not, the treatment may be tailored from the sst receptor expression. This is of great importance for the patients and for the health care system.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 3

Contacts and Locations

Study Locations

• Sweden
  • Göteborg, Sweden, SE-413 45
    • Center of Endocrinology and Metabolism, Sahlgrenska university Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Naïve, unoperated pituitary tumour with GH or ACTH or TSH production or NFPA without treatment with somatostatin analogues or dopamine agonists.

Exclusion Criteria:

• Patient who may not attend to the protocol according to the investigators opinion.
• Pregnancy or lactating
• Isolated prolactin producing tumours
• Overproduction of gonadotrophins
• Carcinoids ie ectopic CRF production
• Known or suspected allergy to the trial product or related products.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ga-68 DOTATOC PET in pituitary adenomas; To give Ga-68 DOTATOC in pituitary patients doing PET/CT They are compared with Ga-68 DOTATOC PET performed in another study on patients with no pituitary disease.	Drug: Gallium-68 DOTATOC PET; The intervention is to administer Ga-68 DOTATOC in pituitary patients doing PET/CT; Other Names: Ga-PET

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SUV max in GA-68 DOTATOC in pituitary tumours in comparison to normal pituitary	Maximum Standardized Uptake Value	Baseline
SUV max in GA-68 DOTATOC in pituitary tumours in comparison to normal pituitary	Maximum Standardized Uptake Value	measured at 6 months +/- 2 weeks from baseline
SUV max in GA-68 DOTATOC in pituitary tumours in comparison to normal pituitary	Maximum Standardized Uptake Value	measured at 36 months +/- 2 weeks from baseline

Secondary Outcome Measures

Outcome Measure	Time Frame
Ga-PET uptake in correlation to sst expression in pituitary tumours, measured as SUVmax which is then used to establish statistical relationship with a cell membrane-based sst-immunohistochemistry (IHC) score"	Baseline
Ga-PET uptake in correlation to sst expression in pituitary tumours, measured as SUVmax which is then used to establish statistical relationship with a cell membrane-based sst-immunohistochemistry (IHC) score"	measured at 6 months +/- 2 weeks from baseline
Ga-PET uptake in correlation to sst expression in pituitary tumours, measured as SUVmax which is then used to establish statistical relationship with a cell membrane-based sst-immunohistochemistry (IHC) score"	measured at 36 months +/- 2 weeks from baseline
Adverse event registration in association to Ga-68 PET	Baseline
Adverse event registration in association to Ga-68 PET	measured at 6 months +/- 2 weeks from baseline
Adverse event registration in association to Ga-68 PET	measured at 36 months +/- 2 weeks from baseline
Detection of tumour recurrence with Ga-PET	measured at 6 months +/- 2 weeks from baseline
Detection of tumour recurrence with Ga-PET	measured at 36 months +/- 2 weeks from baseline

Other Outcome Measures

Outcome Measure	Time Frame
Dynamic measurements of Ga-68 Dotatoc in the pituitary [include the dynamic measure of SUVmax, blood flow,	Baseline
Dynamic measurements of Ga-68 Dotatoc in the pituitary [include the dynamic measure of SUVmax, blood flow,	measured at 6 months +/- 2 weeks from baseline
Dynamic measurements of Ga-68 Dotatoc in the pituitary [include the dynamic measure of SUVmax, blood flow,	measured at 36 months +/- 2 weeks from baseline

Collaborators and Investigators

• Sponsor: Göteborg University
• Collaborators: Uppsala University; Sahlgrenska University Hospital, Sweden
• Investigators: Principal Investigator: Helena Filipsson Nyström, Ass Prof, Center of Endocrinology and Metabolism, Dep of Endorinology, Sahlgrenska University Hospital, Göteborg, Sweden

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Actual): January 13, 2022
• Study Completion (Actual): January 13, 2022

Study Registration Dates

• First Submitted: January 19, 2015
• First Submitted That Met QC Criteria: April 14, 2015
• First Posted (Estimate): April 17, 2015

Study Record Updates

• Last Update Posted (Actual): March 31, 2022
• Last Update Submitted That Met QC Criteria: March 15, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Acromegaly; pituitary; Cushing; pituitary adenomas; Ga-PET; TSHomas
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Endocrine Gland Neoplasms; Hypothalamic Diseases; Hypothalamic Neoplasms; Supratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Pituitary Neoplasms; Pituitary Diseases; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Edotreotide
• Other Study ID Numbers: Ga-PET version 8 (141017); 2010-020482-24 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No