Diagnostic Imaging for Clear Cell Renal Cell Carcinoma

Main objective of the trial:

The main objective is to investigate whether DaTSCAN with subsequent SPECT can detect elevated DAT levels in at least a lesion identified with CT in patients with clear cell renal cell carcinoma, as assesed by pathologist? DaTSCAN signal will be seen as positive, displaying intensity ≥3ggr higher than the background and correlating anatomically with at least one lesion found with CT. DaTSCAN is used routinely to detect the loss of dopaminergic neurons in the striatum of patients with clinically uncertain Parkinsonian Syndromes. The active substance in DaTSCAN, Ioflupane specifically binds to DAT. By analyzing the focal uptake of Ioflupane (123I) with SPECT / CT the progression of the disease may be clarified. In light of our findings that clear cell renal cancer express significantly elevated levels of DAT, we postulate that DaTSCAN can be used for detection of clear cell renal cell carcinoma.

Protection of trial subjects:

Very few adverse effects are reported for DatSCAN use. In this study we used the same dose and route of administration as is praxis for DaTSCAN when used for diagnostic investigation of Parkinsons disease. Albeit uncommon, pain at the injection site has been previously reported when the solution was injected into a small vain. To minimise the potential for pain at the injection site during administration in this study, a slow intravenous injection (not less than 15 to 20 seconds) via an arm vein was therefore applied. The injections were performed by routined staff at Skåne University Hospital, Department of Clinical Physiology / Nuclear Medicine in Malmö, where usual clinical preparedness for allergic reactions after injection was available.

Background therapy:

Patients underwent appropriate thyroid blocking treatment prior to injection of DaTSCAN, to minimise thyroid uptake of radioactive iodine. In this study, this was achieved by oral administration of 2x 65 mg potassium iodide tablettes on the night before the DaTSCAN investigation and another 2x 65 mg potassium iodine tabletts 1 hour prior to injection of DaTSCAN.

• Ioflupane I123 (Drug), also known as DaTSCAN: 185 MBq ioflupane I123 will be administered at one single occasion to the study subjects A one time dose of DaTSCAN is given via intravenous injection of 185 MBq Ioflupane (I123) . The patient takes potassium iodine tablets prior to the DatSCAN injection to protect the thyroid gland. At the time of the DaTSCAN examination, the patient is injected intravenously at slow rate with 185MBq DaTSCAN solution.

Primary outcomes

• Number of Participants That Display Ioflupane-positivity in Tumors Detected Via CT-scan [Through study completion for each participant, an average of 3 months]: The primary endpoint is to investigate if tumors detected with CT display Ioflupane positivity in patients with verified clear cell renal cell carcinoma (ccRCC). Ioflupane signal was considered positive when intensity was >3 times background signal in anatomic position identified as a lesion by CT-scan

Secondary outcomes

• Number of Participants Diagnosed With Non-ccRCC That Display Ioflupane I123-negativity in Tumors Detected Via CT-scan [Through study completion for each participant, an average of 3 months]: Ioflupane I123 displays no positive signal in lesions identifies by CT in patients with tumors classified as non-clear cell renal cell carcinoma

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* suspected kidney cancer diagnosis
* suspected spread of the cancer
* patient is scheduled for surgery alternatively biopsy of kidney tumor
* patient is 18 years or older
* the patient has given their consent to participate in the study
* female patients of reproductive age displays negative pregnancy test

Exclusion Criteria:

* known or suspected allergy to Ioflupane or sodium acetate or acetic acid or ethanol
* patient suffers from moderate to severe renal impairment and exhibits glomerular filtration rate (GFR) <40
* patient is medicated for Parkinson's disease
* patient is medicated with any of the following medications: amphetamine, benzatropine, buproprion, cocaine, mazindol, methylphenidate, phentermine, sertraline, levodopa, dexamphetamine, lisdexamphetamine, modafinil, moclobemid, venlafaxine
* patient is pregnant
* breastfeeding
* patient suffers from mental inability unwillingness or language difficulties resulting in difficulty in understanding the meaning of taking part in the study

Participant flow

Outcome results

• Number of Participants That Display Ioflupane-positivity in Tumors Detected Via CT-scan (Primary), Count of participants, Participants: Experimental Group 0
• Number of Participants Diagnosed With Non-ccRCC That Display Ioflupane I123-negativity in Tumors Detected Via CT-scan (Secondary), Count of participants, Participants: Experimental Group 1

Adverse events

Time frame: AE were reported consecutively for each patient while included in the trial, from potassium iodide intake to two days after Datscan examination, 4 days in total.

Limitations and caveats: Only 5 out of 10 intended patients were recruited in the study due to "early stopping rule" as defined in the study protocol as: terminate study if 4 patients with, by pathologist verified, ccRCC all display negative ioflupane signal in all lesions.

• Study Protocol and Statistical Analysis Plan (PDF, 2016-12-21)

• Peter Elfving, M.D. PhD, Principal investigator, Region Skane

NIH grants: 2016