Neoplasms

All Conditions

Rare Diseases

Neuroendocrine Tumors

Pheochromocytoma

Paraganglioma

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Neuroendocrine Tumor

Paragangliomas 1

Neuroepithelioma

All Drugs and Chemicals

Micronutrients

Anti-Infective Agents

Amino Acids

Endothelial Growth Factors

Mitogens

Iodine

Cadexomer iodine

Tyrosine

Vandetanib (100, 200 or 300 mg once daily) in combination with 131I-mIBG radiation therapy (activity to be prescribed to deliver whole body absorbed dose of 0.5 Gy) on day 1 of each 12-weekly cycle.

Patients will receive up to 4 cycles of vandetanib in combination with 131I-mIBG.

100 mg, 200 mg or 300 mg taken once a day during each 12-weekly cycle

Vandetanib

Activity will be prescribed to deliver whole body absorbed dose of 0.5 Gy (+/-10%)

131I-mIBG

Christina Thirlwell

The phase I trial aims to determine the recommended phase II dose (RP2D) of vandetanib in combination with standard radiation therapy, 131I-mIBG, in patients with advanced phaeochromocytoma (phaeo) and paraganglioma (PG) by assessing the safety and tolerability of the combination treatment.

VIBRaNT is a registered phase I trial in patients with locally advanced or metastatic phaeochromocytoma or paraganglioma, not amenable to surgical resection.

Patients will receive vandetanib (an inhibitor of VEGF, EGFR and RET tyrosine kinase) in combination with standard radiation therapy Iodine-131 labelled Meta-iodobenzylguanidine (131I-mIBG).

Vandetanib and 131I-mIBG will be given in 12-weekly cycles: 131I-miBG will be given on day 1 of each cycle and vandetanib will started on day 1 of each cycle and continue to be taken once every day. The phase I trial aims to determine with recommended phase II dose of vandetanib (either 100, 200 or 300 mg once daily) - the dose of vandetanib that patients will receive will depend on the dose under investigation at the time of patient registration.

The vandetanib dose will be determined by the Modified Continual Reassessment Method (mCRM) - a toxicity model which described the probability of a toxicity occurring at each dose level, which is based on clinical judgement and any available toxicity data.

Phase I Trial of Vandetanib Combined With 131I-mIBG to Treat Patients With Advanced Phaeochromocytoma and Paraganglioma

A Phase I Trial of Vandetanib Combined With 131I-mIBG Radiotherapy in Patients With Neuroendocrine Tumours, Advanced Phaeochromocytoma and Paraganglioma

Detailed adverse event monitoring will be conducted according to CTCAE v4.03. Dose Limiting Toxicity (DLT) is defined as any adverse event or laboratory abnormality detailed in the trial protocol, that is considered to be highly probable or probable trial treatment related and commencing anytime during the DLT evaluation period (from start of cycle 1 to cycle 1 week 12). Adverse Events include: Haematological, Clinical Chemistry, Cardiovascular, Gastrointestinal, Skin.

Response will be assessed according to RECIST v1.1. Confirmation of complete or partial response is not required. Stable disease will be considered the best response only is a second assessment has been carried out which confirmed stable disease at least 4 weeks after trial entry. Assessment will be determined using CT scans and 123I-mIBG scans performed at baseline, then every 3 months after start of treatment until disease progression (up to 3 years from registration)

Will include all grade 1-5 adverse events.

Progression-free survival will be calculated from the date of trial entry to the date of documented disease progression, or death from any cause. Where progression is suspected and subsequently confirmed by scans, the date of documented suspected progression will be used.

Cancer Research UK

AstraZeneca

University College, London

Respiratory Tract (Lung and Bronchial) Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

Gemcitabine

Carboplatin

Docetaxel

Cisplatin

Erlotinib Hydrochloride

Tubulin Modulators

Antimitotic Agents

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Antimetabolites

Erlotinib (Tarceva)150 mg /day

Patients will receive treatment until disease progression or unacceptable toxicity.

For all practical effects a treatment cycle will be defined as three weeks of continuous treatment with erlotinib

4 cycles of Chemotherapy:

Cisplatin / Gemcitabine; Cisplatin /Docetaxel; Carboplatin / Gemcitabine; Carboplatin / Docetaxel.

- Cisplatin plus docetaxel: cisplatin 75 mg/m2 i.v. day 1 and docetaxel 75 mg/m2 i.v.

day 1. Repeat cycles every 3 weeks.

- Cisplatin plus gemcitabine: Cisplatin 75 mg/m2 i.v. on day 1 and gemcitabine 1250 mg/m2 on days 1 and 8. Repeat cycles every 3 weeks.

In the case of patients not eligible for treatment with cisplatin, cisplatin can be replaced by carboplatin. The schedules will be the following:

Docetaxel 75 mg/m2 day 1 and carboplatin AUC = 6 day 1, every 21 days.

Gemcitabine 1000 mg/m2 days 1 and 8 and carboplatin AUC = 5 day 1, every 21 days.

Patients in the chemotherapy arm will receive the treatment until disease progression or unacceptable toxicity occurs, or until a maximum of 4 treatment cycles are given.

150 mg/day Patients will receive treatment until disease progression or unacceptable toxicity.

For all practical effects a treatment cycle will be defined as three weeks of continuous treatment with erlotinib

Erlotinib

Gemcitabine 1000 mg/m2 days 1 and 8 and Carboplatin AUC = 5 day 1, every 21 days.

Docetaxel (75 mg/m2) /carboplatin (AUC=6); Gemcitabine (1000 mg/m2; day 1 and 8) / Carboplatin (AUC=5)

Patients in the chemotherapy arm will receive the treatment until disease progression or unacceptable toxicity occurs, or until a maximum of 4 treatment cycles are given.

Cisplatin (75 mg/m2) / Gemcitabine (1250 mg/m2; day 1 and 8) Patients in the chemotherapy arm will receive the treatment until disease progression or unacceptable toxicity occurs, or until a maximum of 4 treatment cycles are given.

Gemcitabin

Cisplatin (75 mg/m2) / Docetaxel (75 mg/m2) Patients in the chemotherapy arm will receive the treatment until disease progression or unacceptable toxicity occurs, or until a maximum of 4 treatment cycles are given.

Rafael Rosell i Costa, MD

Luis Paz-Ares, MD

A Phase III, multicenter, open-label, randomized trial of Erlotinib (Tarceva®) versus chemotherapy in patients with advanced NSCLC with mutations in the Tyrosine Kinase (TK) domain of the EGFR.

This is a multicenter, phase III, randomized, open-label clinical trial.

146 patients with a diagnosis of advanced (stage IIIB and stage IV), non-squamous-cell, non-small-cell pulmonary carcinoma not treated previously for their disease with chemotherapy who present mutation in the tyrosine kinase domain of the epidermal growth factor receptor, EGFR will be recluted.

The primary objective is to compare the progression-free survival in both treatment arms of the study (conventional chemotherapy vs. erlotinib) in patients with non-squamous-cell, non-small-cell lung cancer (NSCLC) in advanced stage (stages IIIB and stage IV) who have not received previous chemotherapy for their disease and who present mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR).

Phase III Study (Tarceva®) vs Chemotherapy to Treat Advanced Non-Small Cell Lung Cancer in Patients With Mutations in the TK Domain of EGFR

Phase III, Multicenter, Open-label, Randomized Trial of Tarceva® vs Chemotherapy in Patients With Advanced NSCLC With Mutations in the TK Domain of the EGFR

The time from enrollment in the study to tumor progression or death from any cause (whichever occurs first)

The objective response rate is defined as the percentage of patients who attain complete response (CR) or partial response (PR); response will be evaluated following RECIST criteria.

Proportion of patients who are still alive one year after enrollment in the study.

Overall survival will be assessed from the date of enrollment in the study until the date of death from any cause. Patients lost to follow-up will be censured on the date of the last follow-up visit.

Occurrence and severity of adverse events, with severity determined by NCI CTCAE v3.0 criteria

Changes in the scores obtained with the LCSS validated questionnaire throughout the course of the study will be analyzed to assess change in the patient's quality of life.

The study of mutations in serum (serum DNA)

Spanish Lung Cancer Group

Symptoms and General Pathology

Recurrence

Dasatinib

Erlotinib in combination with Dasatinib

Eric B. Haura, MD

This is a single site phase I dose escalation trial of the epidermal growth factor receptor inhibitor Erlotinib with the SRC tyrosine kinase inhibitor Dasatinib in patients with previously treated advanced stage (Stage IIIB/IV disease) Non-Small Cell Lung Cancer (NSCLC). The treatment regimen consists of Erlotinib tablets starting Day 1 and Dasatinib tablets starting Day 9 for a 28-day cycle. If there are no Dose Limiting Toxicities (DLTs), dose escalation continues. The recommended phase II dose for this combined treatment will be defined and patients will be treated at the recommended phase II dose to confirm tolerability.

This is a single site Phase I dose escalation trial of the epidermal growth factor receptor inhibitor Erlotinib with the SRC tyrosine kinase inhibitor Dasatinib in patients with previously treated advanced stage (Stage IIIB/IV disease) Non-Small Cell Lung Cancer (NSCLC). The screening evaluation will consist of a medical history including dates/description of your initial NSCLC diagnosis and documentation of any previous treatment. There will also be a physical examination including vital signs, height, weight, Eastern Cooperative Oncology Group (ECOG)performance status, blood draws for Complete Blood Count (CBC) and Complete Metabolic Panel (CMP) tests, neurological examination, a pregnancy test for female patients of childbearing potential, and (if applicable) any observable tumor measurements all within 14 days before study enrollment. A screening Electrocardiogram (EKG) as well as clinical testing to evaluate all known sites of malignant lesions, including Computed Tomography (CTs) of the chest and upper abdomen, the adrenal glands; ultrasound; or radionuclide scans of the bones; and/or other radiographic studies should be performed within 30 days prior to enrollment.

The treatment regimen consists of Erlotinib tablets starting Day 1 and Dasatinib tablets starting Day 9 for a 28-day cycle. If there are no DLTs, dose escalation continues. Patients continuing on therapy past two cycles will be seen by the treating physician every 4 weeks and will have complete History and Physical (H\&P), CBC, and CMP. Tumor measurement and response assessment will occur every 6-8 weeks. Dasatinib and Erlotinib will be continued until progression of disease, unacceptable toxicity, or patient request.

The recommended phase II dose for this combined treatment will be defined and patients will be treated at the recommended phase II dose to confirm tolerability.

Phase I Dasatinib/Erlotinib in Recurrent Non-small Cell Lung Cancer (NSCLC)

Phase I Trial Evaluating the Epidermal Growth Factor Receptor Inhibitor Erlotinib in Combination With the SRC Kinase Inhibitor Dasatinib for Patients With Recurrent Non-small Cell Lung Cancer (NSCLC)

Determine the safety and tolerability of erlotinib in combination with dasatinib in patients with advanced NSCLC

Determine the MTD of erlotinib in combination with dasatinib and the phase II dose

Characterize the pharmacokinetics of the erlotinib/dasatinib combination

Assess serum angiogenic markers as pharmacodynamic markers of treatment

Estimate the objective response rate (CR and partial response PR). Partial Response is defined as at least a 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference the baseline sum LD. Complete Response is defined as disappearance of all target lesions.

Estimate the 6-month progression free survival rate

Bristol-Myers Squibb

H. Lee Moffitt Cancer Center and Research Institute

Skin and Connective Tissue Diseases

Gland and Hormone Related Diseases

Nervous System Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Diseases and Abnormalities at or Before Birth

Neoplasm Metastasis

Breast Neoplasms

Thyroid Neoplasms

Thyroid Diseases

Glioma

Sarcoma

Brain Neoplasms

Wilms Tumor

Thyroid Cancer, Papillary

Central Nervous System Neoplasms

Medulloblastoma

Neuroblastoma

Sarcoma, Ewing

Fibrosarcoma

Nephroma, Mesoblastic

Nervous System Neoplasms

Soft Tissue Sarcoma

Wilms' Tumor

Papillary Thyroid Carcinoma

Ewing Sarcoma

Congenital Mesoblastic Nephroma

Entrectinib

Arm closed for further enrollment

ROS1, ALK non-gene fusion molecular alterations

Oral entrectinib (RXDX-101)

Arm closed for further enrollment

molecular alterations, including gene fusions

Oral entrectinib (RXDX-101)

Arm closed for further enrollment

Oral entrectinib (RXDX-101)

Arm closed for further enrollment

harboring - NTRK1/2/3, ROS1, ALK gene fusions

Oral entrectinib (RXDX-101)

Arm closed for further enrollment

Any participant who otherwise meet all other eligibility criteria

Oral entrectinib (RXDX-101)

gene fusions

Oral entrectinib (RXDX-101)

NTRK 1,2,3 and ROS1 fusions

Oral entrectinib (RXDX-101)

Clinical Trials

This is an open-label, Phase 1/2 multicenter dose escalation study in pediatric patients with relapsed or refractory extracranial solid tumors (Phase 1), with additional expansion cohorts (Phase 2) in patients with primary brain tumors harboring NTRK1/2/3 or ROS1 gene fusions, and extracranial solid tumors harboring NTRK1/2/3 or ROS1 gene fusions.

Study Of Entrectinib (Rxdx-101) in Children and Adolescents With Locally Advanced Or Metastatic Solid Or Primary CNS Tumors And/Or Who Have No Satisfactory Treatment Options

A Phase 1/2, Open-Label, Dose-Escalation And Expansion Study Of Entrectinib (Rxdx-101) In Pediatrics With Locally Advanced Or Metastatic Solid Or Primary CNS Tumors And/Or Who Have No Satisfactory Treatment Options

Assessed by National Cancer Institute Common Terminology for Adverse Events Criteria (NCI CTCAE v4.03)

AE, ECG and Labs assessed by NCI CTCAE v4.03

Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter

Assessed by RECIST v1.1 per the BICR and investigator

Assessed by RANO per the BICR and investigator

Assessed by the Curie scale per the BICR and investigator

Assessed by RECIST v1.1 per the investigator

Hoffmann-La Roche

Blood and Lymph Conditions

Leukemia

Leukemia, Myeloid

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Hematologic Diseases

Myeloproliferative Disorders

Bone Marrow Diseases

Chronic Disease

Disease Attributes

Myeloid Leukemia

Chronic Graft Versus Host Disease

Chronic Myeloid Leukemia

Chronic Myeloproliferative Disorders

Interferons

Peginterferon alfa-2b

Interferon-alpha

Imatinib Mesylate

Interferon alpha-2

Antiviral Agents

STI571 and PEG INTRON

Michele Baccarani, MD

This is a phase II multicenter, open-label study designed to investigate the feasibility (tolerance, compliance and safety) of a combination of the tyrosine kinase inhibitor STI 571 (GLIVEC, Novartis Pharma) with a pegylated \*-Interferon 2b (PEG INTRON). The rationale for testing this combination is that 1) aIFN is curently the first line agent for the treatment of CML, 2) the pegylated formulation of aIFN is more convenient and is better tolerated than the conventional formulation, 3) STI571 is currently the most promising investigational agent for the treatment of CML because it is targeted to the molecular bases of the disease, is effective also in the advanced phases of the disease, and is effective also in the cases who are resistant to aIFN, 4) the mechanisms of action of the two agents are different. Therefore the combination of STI571 and PEGINTRON is likely to provide the best treatment of CML and to be tested very soon in randomized phase III studies of efficacy. So far STI571 and PEGINTRON have been investigated separately. The present study is an exploratory study that has been planned with the aim of evaluating the adverse events and the safety of the combination, so as to identify a safe and tolerable regime that can be tested prospectively for efficacy in a subsequent, randomized phase III study. Based on available knowledge and data, STI571 is more specific and can be more effective than PEGINTRON. Therefore in this exploratory study STI571 is given a priority over PEGINTRON as to dose and dose adaptation. Sixty subjects with chronic phase CML, previously untreated with any one of study drugs, will be enrolled over a 3 months period and will be treated and studied for 12 months. The patients can be pretreated with hydroxyurea , whenever required, hence are treated with STI 571 at a fixed dose (400mg) and with PEG-Intron at doses ranging from 50 to 150 \*g weekly (the first cohort of 20 patients at 50 \*g/w, the second cohort of 20 patients at 100 \*g/w and the third cohort of 20 patients at 150 \*g/w). The response (hematologic, cytogenetic and molecular) to the combination treatment will be evaluated every 3 months, and the pharmacokinetics of study drugs will be studied in a sample of study patients. The duration of the study is 12 months, for a total trial time of 15 months.

STI 571 and \*IFN are the two single most effective agents for the treatment of CML. Their mechanisms of actions are different. Their toxicity is also different, but both spare normal hemopoietic stem cells. STI 571 is well tolerated, while conventional \*IFN is poorly tolerated, especially in the elderly. PEG \*IFNs are going to substitute for conventional \*IFNs because of a better pharmacokinetic and toxicity profile and because require less injections (once a week vs. once a day).Resistance to IFN (6-13) and to STI571 (29-34) occurs in vitro and in vivo, where it increases with time for IFN and is also expected to increase with time for STI571. STI571 and IFN have different mechanisms of action and it has been shown in vitro that the combination of STI571 with alfaIFN is more toxic than either agent alone against Ph positive cells (35-37). Therefore, a combination of STI 571 with a PEG \*IFN is worth testing. A phase II, dose-finding, exploratory study is required to investigate feasibility, toxicity, safety and tolerability of the combination. In CML, PEG INTRON studies are more advanced than PEGASIS studies. These considerations provide the rationale for this phase II study of STI 571 and PEG INTRON in CML.

Study of the Combination of a Tyrosine Kinase Inhibitor (STI571) and a Pegylated Human Recombinant Interferon alfa2b (PEGINTRON)

An Exploratory Phase II Study of the Combination of a Tyrosine Kinase Inhibitor (STI571) and a Pegylated Human Recombinant Interferon alfa2b (PEGINTRON) in the Treatment of Chronic Myeloid Leukemia in Chronic Phase

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase I Trial of Vandetanib Combined With 131I-mIBG to Treat Patients With Advanced Phaeochromocytoma and Paraganglioma	NCT01941849	Phaeochromocyto... Paraganglioma	Vandetanib 131I-mIBG	18 Years -	University College, London
Phase I Trial of Vandetanib Combined With 131I-mIBG to Treat Patients With Advanced Phaeochromocytoma and Paraganglioma	NCT01941849	Phaeochromocyto... Paraganglioma	Vandetanib 131I-mIBG	18 Years -	University College, London
Phase III Study (Tarceva®) vs Chemotherapy to Treat Advanced Non-Small Cell Lung Cancer in Patients With Mutations in the TK Domain of EGFR	NCT00446225	Non-Small Cell ...	Erlotinib Carboplatin Gemcitabin Docetaxel Cisplatin	18 Years -	Spanish Lung Cancer Group
Phase I Dasatinib/Erlotinib in Recurrent Non-small Cell Lung Cancer (NSCLC)	NCT00444015	Non-Small-Cell ...	Erlotinib in co...	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
Study Of Entrectinib (Rxdx-101) in Children and Adolescents With Locally Advanced Or Metastatic Solid Or Primary CNS Tumors And/Or Who Have No Satisfactory Treatment Options	NCT02650401	Solid Tumors CNS Tumors	Entrectinib	0 Years - 18 Years	Hoffmann-La Roche
Study of the Combination of a Tyrosine Kinase Inhibitor (STI571) and a Pegylated Human Recombinant Interferon alfa2b (PEGINTRON)	NCT00511121	Chronic Myeloid...	STI571 and PEG ...	18 Years - 65 Years	University of Bologna
Vandetanib to Treat Women With Ovarian, Fallopian Tube, or Primary Peritoneal Cancer	NCT00445549	Ovarian Neoplas... Fallopian Tube ... Peritoneal Neop...	Vandetanib	18 Years -	National Institutes of Health Clinical Center (CC)
Vandetanib to Treat Women With Ovarian, Fallopian Tube, or Primary Peritoneal Cancer	NCT00445549	Ovarian Neoplas... Fallopian Tube ... Peritoneal Neop...	Vandetanib	18 Years -	National Institutes of Health Clinical Center (CC)
AZD1775 for Advanced Solid Tumors	NCT01748825	Solid Tumors	MK-1775 (AZD177...	18 Years - 120 Years	National Institutes of Health Clinical Center (CC)
Study Of Entrectinib (Rxdx-101) in Children and Adolescents With Locally Advanced Or Metastatic Solid Or Primary CNS Tumors And/Or Who Have No Satisfactory Treatment Options	NCT02650401	Solid Tumors CNS Tumors	Entrectinib	0 Years - 18 Years	Hoffmann-La Roche

Spots Global Cancer Trial Database for tyrosine kinase