SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT01534897

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

Re-differentiation of Radioiodine-Refractory BRAF V600E-mutant Papillary Thyroid Carcinoma With GSK2118436

Radioactive iodine therapy is often part of the standard treatment for Papillary Thyroid Carcinoma (PTC) patients. However, in many patients, tumors develop a resistance or no longer respond to radioactive iodine therapy (iodine-refractory). Several lines of evidence suggest that blocking the BRAF gene may help to re-sensitize the tumors to radioactive iodine. BRAF is a protein that plays a central role in the growth and survival of cancer cells in some types of PTC. The investigational drug GSK2118436 may work by blocking the BRAF protein in cancer cells lines and tumors that have a mutated BRAF gene. In this research study, the investigators are looking to see if GSK2118436 can re-sensitize iodine-refractory PTC to radioactive iodine therapy. The investigators are also looking at the safety of adding GSK2118436 to radioactive iodine therapy.

NCT01534897 Papillary Thyroid Carcinoma
MeSH: Carcinoma Thyroid Diseases Thyroid Neoplasms Thyroid Cancer, Papillary
HPO: Abnormality of the thyroid gland Carcinoma Neoplasm of the thyroid gland Thyroid adenoma Thyroid carcinoma Thyroid follicular adenoma

1 Interventions

Name: GSK2118436

Description: 150mg twice per day orally for 28 days (42 days if Iodine-131 scan on Day 25 shows new uptake)

Type: Drug

GSK2118436


Primary Outcomes

Description: Number of patients with radioiodine-refractory metastatic BRAF V600E-mutant PTC who have increased radioiodine uptake in their disease sites while on dabrafenib. Radioiodine uptake is assessed by whole body scan and areas of interest are identified by nuclear medicine physicians.

Measure: Increased Radioiodine Uptake

Time: 25 days after start of Dabrafenib (GSK2118436)

Secondary Outcomes

Description: To evaluate the safety and tolerability, as determined by adverse event and serious adverse event reporting, of GSK2118436 in combination with whole body iodine scans (all patients) and treatment doses of radioactive iodine (patients whose tumors demonstrate significant iodine uptake).

Measure: Safety Analysis as Number of Participants With Adverse Events

Time: 2 years

Description: To evaluate clinical benefit as measured by objective response rate per modified RECIST 1.1, which assesses changes in size of measurable tumors. (per RECIST, a partial response (PR) = at least 30% decrease in size of tumor; progressive disease (PD) = at least 20% increase in size of tumor; stable disease (SD) = neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD).

Measure: Clinical Benefit as Measured by Change in Tumor Size

Time: 2 years

Description: To determine the feasibility of: (a) administering GSK2118436 for 28 days in patients with BRAF V600E-mutant PTC, prior to whole body iodine scanning (all patients); and (b) administering GSK2118436 for an additional 14 days, prior to administering treatment doses of radioactive iodine (patients whose tumors demonstrate significant iodine uptake after 28 days of treatment).

Measure: Number of Participants Who Complete the Study With Minimal Delays and no Dose Reductions

Time: 2 years

Description: To evaluate clinical benefit as measured by change in serum tumor marker, thyroglobulin. Rising thyroglobulin is generally indicative of tumor growth.

Measure: Clinical Benefit as Measured by Change in Thyroglobulin Level

Time: 3 months after radioiodine therapy

Purpose: Treatment

Single Group Assignment


There is one SNP

SNPs


1 V600E

Re-differentiation of Radioiodine-Refractory BRAF V600E-mutant Papillary Thyroid Carcinoma With GSK2118436. --- V600E ---

Re-differentiation of Radioiodine-Refractory BRAF V600E-mutant Papillary Thyroid Carcinoma With GSK2118436 Radioactive iodine therapy is often part of the standard treatment for Papillary Thyroid Carcinoma (PTC) patients. --- V600E ---

Number of patients with radioiodine-refractory metastatic BRAF V600E-mutant PTC who have increased radioiodine uptake in their disease sites while on dabrafenib. --- V600E ---

To determine the feasibility of: (a) administering GSK2118436 for 28 days in patients with BRAF V600E-mutant PTC, prior to whole body iodine scanning (all patients); and (b) administering GSK2118436 for an additional 14 days, prior to administering treatment doses of radioactive iodine (patients whose tumors demonstrate significant iodine uptake after 28 days of treatment).. Clinical Benefit as Measured by Change in Thyroglobulin Level. --- V600E ---

Rising thyroglobulin is generally indicative of tumor growth.. Inclusion Criteria: - Histologically confirmed papillary thyroid carcinoma, including its variants, such as tall cell PTC or poorly differentiated thyroid carcinoma, that is metastatic or unresectable AND harbors a BRAF V600E mutation - Evaluable disease, as defined by at least one lesion that can be accurately measured in at least one dimension on CT scan or ultrasound, if present in the neck - Radioiodine-refractory disease - Life expectancy > 6 months - Able to swallow and retain oral medication - Normal organ and marrow function Exclusion Criteria: - Pregnant or breastfeeding - Previous treatment with a specific BRAF or MEK inhibitor - Receiving any other study agents - Known brain metastases - History of allergic reactions attributed to compounds of similar chemical or biologic composition to GSK2118436, bovine TSH, mannitol or iodine - Active gastrointestinal disease or other condition that will interfere significantly with the absorption of drugs - History of known glucose-6-phosphate dehyrogenase (G6PD) deficiency - Corrected QT interval >/= 480 msecs; history of acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting within the past 24 weeks; Class II, III, or IV heart failure, abnormal cardiac valve morphology; or history of known cardiac arrhythmias - Taking herbal remedies - Subjects with significant symptoms from their thyroid cancer, or have a large burden of rapidly progressive iodine-refractory PTC who are in need of other systemic therapy, as judged by their treating physician - Uncontrolled current illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension or psychiatric illness/social situations that would limit compliance with study requirements - History of a different malignancy unless disease-free for at least 5 years and deemed to be at low risk for recurrence - HIV-positive on combination antiretroviral therapy Inclusion Criteria: - Histologically confirmed papillary thyroid carcinoma, including its variants, such as tall cell PTC or poorly differentiated thyroid carcinoma, that is metastatic or unresectable AND harbors a BRAF V600E mutation - Evaluable disease, as defined by at least one lesion that can be accurately measured in at least one dimension on CT scan or ultrasound, if present in the neck - Radioiodine-refractory disease - Life expectancy > 6 months - Able to swallow and retain oral medication - Normal organ and marrow function Exclusion Criteria: - Pregnant or breastfeeding - Previous treatment with a specific BRAF or MEK inhibitor - Receiving any other study agents - Known brain metastases - History of allergic reactions attributed to compounds of similar chemical or biologic composition to GSK2118436, bovine TSH, mannitol or iodine - Active gastrointestinal disease or other condition that will interfere significantly with the absorption of drugs - History of known glucose-6-phosphate dehyrogenase (G6PD) deficiency - Corrected QT interval >/= 480 msecs; history of acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting within the past 24 weeks; Class II, III, or IV heart failure, abnormal cardiac valve morphology; or history of known cardiac arrhythmias - Taking herbal remedies - Subjects with significant symptoms from their thyroid cancer, or have a large burden of rapidly progressive iodine-refractory PTC who are in need of other systemic therapy, as judged by their treating physician - Uncontrolled current illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension or psychiatric illness/social situations that would limit compliance with study requirements - History of a different malignancy unless disease-free for at least 5 years and deemed to be at low risk for recurrence - HIV-positive on combination antiretroviral therapy Papillary Thyroid Carcinoma Carcinoma Thyroid Diseases Thyroid Neoplasms Thyroid Cancer, Papillary You will take GSK2118436 capsules by mouth for 28 straight days. --- V600E ---

Rising thyroglobulin is generally indicative of tumor growth.. Inclusion Criteria: - Histologically confirmed papillary thyroid carcinoma, including its variants, such as tall cell PTC or poorly differentiated thyroid carcinoma, that is metastatic or unresectable AND harbors a BRAF V600E mutation - Evaluable disease, as defined by at least one lesion that can be accurately measured in at least one dimension on CT scan or ultrasound, if present in the neck - Radioiodine-refractory disease - Life expectancy > 6 months - Able to swallow and retain oral medication - Normal organ and marrow function Exclusion Criteria: - Pregnant or breastfeeding - Previous treatment with a specific BRAF or MEK inhibitor - Receiving any other study agents - Known brain metastases - History of allergic reactions attributed to compounds of similar chemical or biologic composition to GSK2118436, bovine TSH, mannitol or iodine - Active gastrointestinal disease or other condition that will interfere significantly with the absorption of drugs - History of known glucose-6-phosphate dehyrogenase (G6PD) deficiency - Corrected QT interval >/= 480 msecs; history of acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting within the past 24 weeks; Class II, III, or IV heart failure, abnormal cardiac valve morphology; or history of known cardiac arrhythmias - Taking herbal remedies - Subjects with significant symptoms from their thyroid cancer, or have a large burden of rapidly progressive iodine-refractory PTC who are in need of other systemic therapy, as judged by their treating physician - Uncontrolled current illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension or psychiatric illness/social situations that would limit compliance with study requirements - History of a different malignancy unless disease-free for at least 5 years and deemed to be at low risk for recurrence - HIV-positive on combination antiretroviral therapy Inclusion Criteria: - Histologically confirmed papillary thyroid carcinoma, including its variants, such as tall cell PTC or poorly differentiated thyroid carcinoma, that is metastatic or unresectable AND harbors a BRAF V600E mutation - Evaluable disease, as defined by at least one lesion that can be accurately measured in at least one dimension on CT scan or ultrasound, if present in the neck - Radioiodine-refractory disease - Life expectancy > 6 months - Able to swallow and retain oral medication - Normal organ and marrow function Exclusion Criteria: - Pregnant or breastfeeding - Previous treatment with a specific BRAF or MEK inhibitor - Receiving any other study agents - Known brain metastases - History of allergic reactions attributed to compounds of similar chemical or biologic composition to GSK2118436, bovine TSH, mannitol or iodine - Active gastrointestinal disease or other condition that will interfere significantly with the absorption of drugs - History of known glucose-6-phosphate dehyrogenase (G6PD) deficiency - Corrected QT interval >/= 480 msecs; history of acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting within the past 24 weeks; Class II, III, or IV heart failure, abnormal cardiac valve morphology; or history of known cardiac arrhythmias - Taking herbal remedies - Subjects with significant symptoms from their thyroid cancer, or have a large burden of rapidly progressive iodine-refractory PTC who are in need of other systemic therapy, as judged by their treating physician - Uncontrolled current illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension or psychiatric illness/social situations that would limit compliance with study requirements - History of a different malignancy unless disease-free for at least 5 years and deemed to be at low risk for recurrence - HIV-positive on combination antiretroviral therapy Papillary Thyroid Carcinoma Carcinoma Thyroid Diseases Thyroid Neoplasms Thyroid Cancer, Papillary You will take GSK2118436 capsules by mouth for 28 straight days. --- V600E --- --- V600E ---



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
Carcinoma
Genes 11
PTEN CDKN1B APC MLH1 MSH2 FGFR3 KIT DKC1 RSPO1 STK11 NLRP1
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