SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT02088645

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

177Lu-PP-F11N for Receptor Targeted Therapy and Imaging (Theranostics) of Metastatic Medullary Thyroid Cancer - a Pilot and a Phase I Study.

The purpose of this study is to determine the use of 177Lu-PP-F11N for imaging and therapy of patients with advanced medullary thyroid carcinoma (MTC). 177Lu-PP-F11N is a gastrin analogon, binding to cholecystokinin-2 receptors. This receptors show an overexpression on more than 90 % of medullary thyroid carcinomas. In the pilot (phase 0) study investigators will correlate the tumour detection rate with the surgery and histology (proof of concept study). Furthermore, kidney protection and dosimetry studies will be performed in order to determine the kidney protection protocol and starting activity for the dose escalation study in the following, dose escalation (phase I) study. In the phase I study investigators will determinate the maximum tolerated dose of 177Lu-PP-F11N in patients with MTC. Furthermore, correlation with tumour radiation dose and treatment response as well as organ radiation doses and maximal tolerated dose will be performed in order to allow prospective individual patient tailored therapy planning.

NCT02088645 Thyroid Cancer, Medullary
MeSH: Thyroid Diseases Thyroid Neoplasms Carcinoma, Neuroendocrine
HPO: Abnormality of the thyroid gland Neoplasm of the thyroid gland Thyroid adenoma Thyroid carcinoma Thyroid follicular adenoma

1 Interventions

Name: 177Lu-PP-F11N

Type: Drug

Phase 0: One arm; Phase I: One arm


Primary Outcomes

Description: Phase 0 study: Evaluation of the scintigraphic visualisation of metastases after test injection, verification of 177Lu-PP-F11N uptake in metastases and correlation with surgery/histology if possible (poof of principle study).

Measure: Phase 0: Scintigraphic visualisation rate

Time: up to 4 weeks

Description: Phase I study: Determination of the maximum tolerated dose (MTD)

Measure: Phase I: Maximum tolerated dose

Time: Up to 9 months

Secondary Outcomes

Description: Evaluation of the kidney radiation dose and the tumour-to-kidney radiation dose ratios with and without kidney protection (Physiogel). Composite measure.

Measure: Phase 0: Tumour-to-kidney radiation doses

Time: 8 and 16 weeks

Description: Calculation of tumour and organ radiation doses.

Measure: Phase 0: Radiation doses

Time: 8 and 16 weeks

Description: Evaluation of in vivo stability of 177Lu-PP-F11N.

Measure: Phase 0: In vivo stability

Time: 8 and 16 weeks

Description: Measurement of the metabolites of 177Lu-PP-F11N with and without Physiogel infusion.

Measure: Phase 0: Metabolites

Time: 8 and 16 weeks

Description: Evaluation of side reactions of 177Lu-PP-F11N.

Measure: Phase I: Side reactions

Time: 8, 16 and 24 weeks

Description: Evaluation of biochemical response (decrease of calcitonin and calculation of calcitonin doubling time).

Measure: Phase 1: Biochemical response

Time: For the duration of 24 months.

Description: Evaluation of morphological therapy response (RECIST criteria).

Measure: Phase I: Morphological response

Time: 0, 3 and 12 months

Description: Determination of the tumour detection rate and correlation with surgery/histology, if possible.

Measure: Phase I: Tumour detection rate

Time: 8, 16 and 24 weeks

Description: Calculation of organ radiation doses after therapy and correlation with the determined MTD (composite measure).

Measure: Phase I: Organ radiation doses

Time: 8, 16 and 24 weeks

Description: Determination of overall survival of patients after therapy.

Measure: Phase 1: Overall survival

Time: Up to 5 years

Description: Evaluation of in vivo stability of 177Lu-PP-F11N.

Measure: Phase 1: In vivo stability

Time: 8, 16 und 24 weeks

Description: Measurement of the metabolites of 177Lu-PP-F11N.

Measure: Phase 1: Metabolites

Time: 8, 16 and 24 weeks

Purpose: Treatment

Single Group Assignment


There is one SNP

SNPs


1 F11N

177Lu-PP-F11N for Receptor Targeted Therapy and Imaging (Theranostics) of Metastatic Medullary Thyroid Cancer - a Pilot and a Phase I Study.. 177Lu-PP-F11N for Receptor Targeted Therapy and Imaging of Metastatic Thyroid Cancer. --- F11N ---

177Lu-PP-F11N for Receptor Targeted Therapy and Imaging (Theranostics) of Metastatic Medullary Thyroid Cancer - a Pilot and a Phase I Study.. 177Lu-PP-F11N for Receptor Targeted Therapy and Imaging of Metastatic Thyroid Cancer. --- F11N --- --- F11N ---

The purpose of this study is to determine the use of 177Lu-PP-F11N for imaging and therapy of patients with advanced medullary thyroid carcinoma (MTC). --- F11N ---

177Lu-PP-F11N is a gastrin analogon, binding to cholecystokinin-2 receptors. --- F11N ---

In the phase I study investigators will determinate the maximum tolerated dose of 177Lu-PP-F11N in patients with MTC. --- F11N ---

Phase 0 study: Evaluation of the scintigraphic visualisation of metastases after test injection, verification of 177Lu-PP-F11N uptake in metastases and correlation with surgery/histology if possible (poof of principle study).. Phase I: Maximum tolerated dose. --- F11N ---

Evaluation of in vivo stability of 177Lu-PP-F11N.. Phase 0: Metabolites. --- F11N ---

Measurement of the metabolites of 177Lu-PP-F11N with and without Physiogel infusion.. Phase I: Side reactions. --- F11N ---

Evaluation of side reactions of 177Lu-PP-F11N.. Phase 1: Biochemical response. --- F11N ---

Evaluation of in vivo stability of 177Lu-PP-F11N.. Phase 1: Metabolites. --- F11N ---

Measurement of the metabolites of 177Lu-PP-F11N.. Inclusion Criteria: Phase 0 study - Advanced MTC with elevated levels of calcitonin (> 100 pg/ml) and/or calcitonin-doubling time < 24 months before or after total thyroidectomy - Age > 18 years - Informed consent Phase I study - Diagnostic, contrast medium enhanced CT scan neck/thorax/abdomen, not older than 4 weeks - Advanced MTC with elevated levels of calcitonin (> 100 pg/ml) and/or calcitonin-doubling time < 24 months before or after total thyroidectomy- Age > 18 Years - Informed consent - Curative surgical therapy not possible Exclusion Criteria: Phase 0 study - Medication with Vandetanib 3 weeks before the study and during the study - Renal failure (calculated glomerular filtration rate (GFR) < 60 ml/min per 1.73 m2 body surface). --- F11N ---



HPO Nodes


HPO:
Abnormality of the thyroid gland
Genes 327
CDKN1A PCSK1 SOX3 CDKN1B GABRD TPO CDKN2B CDKN2C UBR1 IL12A TMEM67 IL12RB1 TREX1 PDE4D ZBTB20 PLVAP TRH STUB1 WDR4 SPIB TRHR MCM8 DNAJC19 MARS USP9X ENPP1 HLA-DRB1 PIEZO1 SLC26A4 ACP5 IQSEC2 GAS1 INSR MC2R GATA1 GATA6 CDH23 IRF5 RPS20 SRY TSC1 TSC2 GCH1 EXT2 TSHB TSHR KEAP1 EYA1 PTCH1 RREB1 PTEN BCOR ADA HNF4A ADAR TRIP13 GDNF ALX4 DDOST STAR HESX1 STAT1 PHF21A STAT3 TBC1D24 HIRA MEN1 NSDHL IFIH1 DACT1 BMP4 MALT1 SAA1 BMPR1A ARL6IP6 KISS1R SALL1 ALMS1 BRAF PROKR2 CLPB CLCNKB PIK3C2A PAX8 HPD PIK3CA FDX2 SGPL1 GLI2 GLI3 JAG1 KCNJ10 RNASEH2C SCN4A UFD1 BUB1 ARNT2 BUB1B VPS13A HRAS DCAF17 C1QBP MLH1 C1S ALG8 FGF8 AKT1 KIAA0556 BCL10 FGFR1 PLCG2 CDC73 GNAS SEMA4A HSD17B3 FOXH1 NODAL EIF2AK3 KDM6A TNFSF15 TRAPPC9 SEC23B TBX1 SDHB SDHC SDHD CDON FOXI1 GP1BB PMM2 TBX2 FOXP3 DUOXA2 FOXE1 PMS1 NPHS1 RNASEH2B KRAS CACNA1C RAG1 RAG2 FLII CACNA1S TCF4 SEMA3C HNF1B DMXL2 PMS2 FBLN5 ADAMTSL1 B3GLCT DEAF1 FMR1 NRAS LHX4 COMT SASH1 SLC25A4 GNE TCOF1 CLIP2 NRTN RNASEH2A WFS1 GPR35 NTRK1 RRM2B POLG EFEMP2 POLR1C WRN IYD KCNAB2 GLIS3 POMC APC SHH AIRE BAZ1B POU1F1 BIRC3 DUOX2 POU2AF1 CASP10 DNM1L CP TWNK NLRP1 CASR POU3F4 SAMHD1 MSH2 CHD7 MSH3 TDGF1 LHX3 AIP IDH1 MINPP1 IDH2 TXNRD2 RET RBM28 APOE RFC2 XRCC4 SIX1 SIX3 GTF2IRD1 ECE1 SKI DLL1 FAS FASLG TF EXOSC2 DICER1 JMJD1C ABCC6 LEP OPA1 LEPR MSTO1 EDN3 EDNRB POLR3A ZIC2 DNAH1 FAN1 TG SLC5A5 TTC7A MST1 RMRP TGFBR2 GPR161 LIFR POLR1D TGIF1 MSH6 RASGRP1 MLXIPL LIG4 SEMA3D LIMK1 KLLN KMT2D MLH3 OTX2 GTF2I MMEL1 THRA THRB SLC12A3 SEC24C LMNA COX1 COX2 COX3 IGH ARVCF WDR11 DCLRE1C SUGCT SLC16A2 NKX2-1 RCBTB1 CCBE1 FANCI BTNL2 PPP1R15B MRAP ND1 SETBP1 ND4 ND5 ND6 PTRH2 PRKAR1A LRP4 FLCN STEAP3 NKX2-5 ROBO1 PRKCD FOXP1 TRNF HABP2 TRNH FUCA1 ELN TRNL1 TRNL2 RERE CTNS GREM1 TRNN LRBA CTNNB1 KCNJ18 IGSF1 TRNQ TANGO2 TRNS1 TRNS2 BUB3 POLG2 FUT8 TRNW KAT6B HBB SUFU CEP57 IL2RA EPCAM PRDM16 IL2RG NNT TNPO3 TBL2 DISP1 RAI1 IL7R PROP1 SEMA3E GABRA3 NIN
Neoplasm of the thyroid gland
Genes 61
FOXE1 CDKN1A PMS1 CDKN1B KRAS CDKN2B CDKN2C TGFBR2 MSH6 RASGRP1 SEMA3D SEMA3C BMPR1A PMS2 KLLN MLH3 NRAS LMNA NRTN PIK3CA NTRK1 SLC26A4 JAG1 KCNJ10 WRN HRAS APC MLH1 PRKAR1A FLCN CASP10 PRKCD AKT1 RPS20 HABP2 MSH2 MSH3 CDC73 KEAP1 GREM1 MINPP1 GNAS SEMA4A RET PTEN ECE1 FAS FASLG EPCAM GDNF DICER1 SEC23B EDN3 EDNRB SDHB SDHC SDHD FOXI1 MEN1 FAN1 TG
Thyroid adenoma
Genes 16
PTEN CDKN1A FAS CDKN1B FASLG PRKAR1A CDKN2B CDKN2C PIK3CA CASP10 PRKCD RASGRP1 AKT1 MSH3 CDC73 MEN1
Thyroid carcinoma
Genes 34
FOXE1 HRAS APC PRKAR1A FLCN CASP10 PRKCD RASGRP1 AKT1 BMPR1A HABP2 KLLN CDC73 KEAP1 GREM1 MINPP1 RET NRAS PTEN FAS FASLG PIK3CA DICER1 NTRK1 SEC23B SLC26A4 JAG1 KCNJ10 SDHB SDHC SDHD FOXI1 TG WRN
Thyroid follicular adenoma