Gland and Hormone Related Diseases

All Conditions

Neoplasms

Thyroid Diseases

Carcinoma

Thyroid Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Endocrine System Diseases

Endocrine Gland Neoplasms

Head and Neck Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Doxorubicin

Liposomal doxorubicin

Cisplatin

liposomal doxorubicin(PLD) 35 mg/m2,iv,d1, plus cisplatin 75 mg/m2,drip,d1-3, once every 21days, for 6 cycles, to progression or intolerance.

intravenous infusion of liposomal doxorubicin 35 mg/m2, d1,once every 21days, for 6 cycles.

cisplatin 75 mg/m2, drip, total dose should be carried out on d1-3; once every 21days, for 6 cycles.

jiandong nie, doctor

haiyan yang, doctor

minghua ge, doctor

This is a prospective, multicenter, open label Phase II Clinical Trial. 30 advanced poorly differentiated thyroid carcinoma patients who were histopathologically confirmed inoperable were enrolled in this study.

Subjects will receive the treatment regimen as follow:

intravenous infusion of liposomal doxorubicin 35 mg/m2, d1; cisplatin 75 mg/m2, drip, total dose should be carried out on d1-3; once every 21days, for 6 cycles. Stop the treatment if the patients have progressed or intolerated to the toxicity. The primary endpoint is disease control rate(DCR), the secondary endpoint is overall survival (OS), progression-free survival (PFS), safety and quality of life assessment(QoL).

PLD Combined With Cisplatin in the Treatment of Advanced Poorly Differentiated Thyroid Carcinoma

A Prospective, Multicenter, Open Label Phase Ⅱ Clinical Trial of Doxorubicin Hydrochloride Liposome Injection Combined With Cisplatin in the Treatment of Advanced Poorly Differentiated Thyroid Carcinoma

Evaluate the adverse reaction rate of drugs assessed by number and severity of adverse events in the treatment of advanced thyroid poorly differentiated carcinoma.

Evaluate the QoL according to Functional Assessment of Cancer Therapy.

CSPC ZhongQi Pharmaceutical Technology Co., Ltd.

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Thyroid Cancer, Papillary

Leukemia-Lymphoma, Adult T-Cell

Adenocarcinoma

Adenocarcinoma, Papillary

Papillary Thyroid Carcinoma

Adult T-cell Leukemia/lymphoma

Micronutrients

Anti-Infective Agents

Dabrafenib

Iodine

Cadexomer iodine

Protein Kinase Inhibitors

Enzyme Inhibitors

Intervention: GSK2118436 (dabrafenib) 150mg by mouth twice per day for 28 days, continued to day 42 if the Day 25 Iodine-131 scan shows new uptake. Patients with new Iodine-131 uptake on Day 25 who continue dabrafenib to day 42 receive a treatment dose (150 mCi) of Iodine-131 on Day 37.

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

GSK2118436

Stephen M Rothenberg, MD, PhD

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.

You will take GSK2118436 capsules by mouth for 28 straight days. If your Day 28 whole body radioactive iodine scan demonstrates significant uptake of iodine, you will take GSK2118436 for an additional 14 days (Days 29-42). You will be given a drug diary to record when you take GSK2118436. This diary will also contain instructions on how to take GSK2118436.

Prior to Day 1

* Optional fine needle aspirate (pre-treatment) Day 1
* Vital signs
* Routine blood tests (2 tablespoons)
* Research blood sample for Circulating Tumor Cells (CTCs). (4 teaspoons of blood)
* Optional research blood sample for CTCs 4-6 hours after the first dose of GSK2118436

Day 2:

* Optional research blood sample for CTCs 4-6 hours after the first dose of GSK2118436 Day 3-5: Research blood sample for CTCs Days 8 and 15
* Vital signs
* Routine blood tests (2 tablespoons)
* Research blood sample for CTCs. (4 teaspoons of blood)
* Optional fine needle aspirate (Day 15 only) Low Iodine Diet: You will begin a low iodine diet on Day 15, in preparation for Day 23 when you will receive radioactive iodine (131I). The study team will provide you with instructions on this diet. The low iodine diet will be continued until the whole body scan is complete. For those participants who will receive a therapeutic dose of radioactive iodine on Day 37, the low iodine diet will be continued until the Day 42 whole body scan is complete.

Days 21 and 22: The drug thyrogen will be administered as in injection into your buttocks on Days 21 and 22 in preparation for your whole body radioactive iodine scan on Day 28. Thyrogen is used as a diagnostic tool to help determine the status of your cancer and is approved for use in thyroid cancer patients.

Day 23: To prepare for the whole body radioactive iodine scan, you will be asked to swallow a capsule of radioactive iodine which will be absorbed by any remaining thyroid cells in your body. Radioactive iodine is approved for use in thyroid cancer patients. You will then be asked to return for the scan on Day 28.You will be asked to sign a separate consent for the radioactive iodine.

Days 1-28:

* Optional repeat fine needle aspirate Day 28
* Whole body radioactive iodine scan to assess your thyroid cancer

If your Day 28 whole body radioactive iodine scan demonstrates significant uptake of iodine, you will have the following tests done within 24 hours:

* Vital signs
* Routine blood tests (2 tablespoons)
* Research blood sample for CTCs. (4 teaspoons of blood)
* An injection of a therapeutic dose of radioactive iodine will be administered. If your Day 28 whole body radioactive iodine scan does not demonstrate significant uptake of iodine, you will be removed from the research study. You will have a 3 month follow up appointment as outlined below.

If your Day 28 whole body radioactive iodine scan demonstrates significant uptake of iodine, you will continue treatment with GSK2118436 and have the following study visits:

Days 35 and 36: The drug thyrogen will be administered as in injection into your buttocks on Days 35 and 36 in preparation for your whole body radioactive iodine scan on Day 42.

Day 37: You will be given a therapeutic dose of radioactive iodine. You will be given a separate consent form to sign for your radioactive iodine treatment. You will then be asked to return for the whole body radioactive iodine scan on Day 42.

Day 39:

* Vital signs
* Routine blood tests (1 tablespoon)

Day 42:

* Whole body radioactive iodine scan
* Research blood sample for CTCs. (4 teaspoons of blood)

After the final dose of the study drug: All participants will have a follow up visit 3 months after you stop the study drug. You will have the following tests at this visit:

* Routine blood tests (2 tablespoons)
* Research blood sample for CTCs. (4 teaspoons of blood)
* An assessment of your tumor by CT scan or PET/CT scan of your neck, chest, abdomen and pelvis.
* Those participants who had a therapeutic dose of radioactive iodine on Day 37 will have a whole body radioactive iodine scan.
* Optional fine needle aspirate

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

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.

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).

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).

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).

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

GlaxoSmithKline

Massachusetts General Hospital

Attending Physician

Intervention: GSK2118436 (dabrafenib) 150mg by mouth twice per day for 28 days, continued to day 42 if the Day 25 Iodine-131 scan shows new uptake. Patients with new Iodine-131 uptake on Day 25 who continue dabrafenib to day 42 receive a treatment dose (150 mCi) of Iodine-131 on Day 37.

GSK2118436: 150mg twice per day orally for 28 days (42 days if Iodine-131 scan on Day 25 shows new uptake)

<=18 years

Between 18 and 65 years

>=65 years

Age, Customized

Sex: Female, Male

United States

Region of Enrollment

Type of tumor

Prior radioiodine treatments per patient

Prior surgeries per patient (not including initial thyroidectomy)

Prior external-beam radiotherapy

Prior chemotherapy

Prior targeted therapy

Dr. Lori J. Wirth

Increased Radioiodine Uptake

All patients completed dabrafenib without dose modification.

Safety Analysis as Number of Participants With Adverse Events

Clinical Benefit as Measured by Change in Tumor Size

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

Clinical Benefit as Measured by Change in Thyroglobulin Level

Note: This is a single arm feasibility study.

Intervention: GSK2118436 (dabrafenib) 150mg by mouth twice per day for 28 days, continued to day 42 if the Day 25 Iodine-131 scan shows new uptake. Patients with new Iodine-131 uptake on Day 25 who continue dabrafenib to day 42 receive a treatment dose (150 mCi) of Iodine-131 on Day 37.

GSK2118436: 150mg twice per day orally for 28 days (42 days if Iodine-131 scan on Day 25 shows new uptake)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
PLD Combined With Cisplatin in the Treatment of Advanced Poorly Differentiated Thyroid Carcinoma	NCT03387943	Poorly Differen...	PLD Cisplatin	18 Years - 70 Years	CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Re-differentiation of Radioiodine-Refractory BRAF V600E-mutant Papillary Thyroid Carcinoma With GSK2118436	NCT01534897	Papillary Thyro...	GSK2118436	18 Years -	Massachusetts General Hospital
PLD Combined With Cisplatin in the Treatment of Advanced Poorly Differentiated Thyroid Carcinoma	NCT03387943	Poorly Differen...	PLD Cisplatin	18 Years - 70 Years	CSPC ZhongQi Pharmaceutical Technology Co., Ltd.

Spots Global Cancer Trial Database for poorly differentiated thyroid carcinoma