Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Eye Diseases

Infections

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Diseases and Abnormalities at or Before Birth

Rare Diseases

Carcinoma

Glioblastoma

Neuroblastoma

Sarcoma

Lung Neoplasms

Retinoblastoma

Virus Diseases

Wilms Tumor

Medulloblastoma

Sarcoma, Ewing

Carcinoid Tumor

Rhabdomyosarcoma

Rhabdomyosarcoma, Alveolar

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Soft Tissue Sarcoma

Wilms' Tumor

Ewing Sarcoma

Rhabdomyosarcoma Alveolar

Neuroendocrine Tumor

Neuroepithelioma

Dose escalation (starting at 1 × 10\^7 vp/kg), IV (in the vein) over 1 hour in a single administration

Seneca Valley Virus (biological agent)

Rudin Charles, MD, PhD

The primary purpose of the study is to determine if Seneca Valley Virus may be administered safely to patients with certain types of advanced cancer.

This is the first study in man of Seneca Valley Virus, a virus which seeks and kills certain tumors in non-human model systems. Subjects in this trial will be patients with advanced cancer displaying certain specified neuroendocrine features, pathologically; they will have exhausted standard methods of treatment for their tumor. The primary purpose of the trial is to determine if the virus may be administered safely. Additional purposes are to learn about the distribution of the virus in the body, the elimination of the virus from the body, the immune response to the virus and whether the virus might have some beneficial effects upon the tumors which the patients have. The first patients will be treated with low amounts of virus and subsequent patients may receive higher amounts. At the end of the trial, it is intended to select a dose for further study.

Safety Study of Seneca Valley Virus in Patients With Solid Tumors With Neuroendocrine Features

Phase I Dose-Escalation Study of Seneca Valley Virus (SVV-001), a Replication-Competent Picornavirus, in Patients With Advanced Solid Tumors With Neuroendocrine Features

Neotropix

Margaret Valnoski, President

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Docetaxel

Mitogens

Lapatinib

Tubulin Modulators

Antimitotic Agents

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

dose level Lapatinib (OD) Docetaxel (q3wks) Systematic Growth factor Minus 0 1250 mg 75 mg/m2 + systematic growth factor support

0, 1250mg 75 mg/m2 No

+1 1500mg 75mg/m2 No

Minus +1\* 1500mg 75mg/m2 + systematic growth factor support

+2 1250mg 100mg/m2 No

Minus +2\* + systematic growth factor support

+3 1500mg 100mg/m2 No

Minus +3\* + systematic growth factor support

Apart within the minus dose levels, G-CSF support should be added only as rescue strategy if severe neutropenia occurred during the first cycle of studied dose.Patients will receive 4 cycles of the association. In case of benefit of the treatment, they should continue the treatment with lapatinib until progression.\* patients will be included at level "minus X" only if 2 DLT out of 6 patients based on febrile neutropenia occurred at level "X"

escalation dose from 1250 to 1500 mg in association with docetaxel

lapatinib

escalation dose from 75 mg/m2 to 100 mg/m2 in association with lapatinib

docetaxel

Nicolas Isambert, MD

The objective of this phase I/ II study is therefore to assess the safety and efficacy of lapatinib in combination with docetaxel in patients with advanced cancer. Only patients in first line treatment for metastatic disease should be included in the present study. It is proposed to start with a phase I part evaluating the safety of lapatinib 1250 mg with docetaxel 75 mg/m² without systematic support of growth factors, starting after the completion and data from the 1000 mg lapatinib +75 mg/m² docetaxel dose level in the EORTC (Bonnefoi) study.The objective of the phase II part will confirm the safety and evaluate efficacy of lapatinib in combination with docetaxel.

Docetaxel is a major drug in the treatment of metastatic breast cancer. In HER2 negative tumor, the first line treatment is based on docetaxel containing regimen: docetaxel alone, docetaxel + anthracycline or docetaxel + capecitabine. The efficacy of docetaxel in combination with trastuzumab has been demonstrated in first line metastatic breast cancer overexpressing erbB2 receptor. The response rate (RR) and the time to progression (TTP) observed were even higher than those obtained with paclitaxel +trastuzumab. Docetaxel is more and more used in first line metastatic setting, becoming the first Taxane used in this setting.As trastuzumab may raise safety/tolerability concerns, and as its interest in trastuzumab refractory patients may be limited, there is a need to find new drugs to combine with docetaxel in breast cancer, and to address the specific interaction/safety profile of this combination.The association of lapatinib and docetaxel will be the key combination in metastatic breast cancer development for GSK.The conclusion of a phase I trial EGF 10021 trial conducted in the US which assessed the combination of lapatinib and docetaxel showed that the acceptable optimal tolerated regimen (OTR) of docetaxel (75 mg/m²) was obtained in combination with lapatinib 1250 mg with systematic growth factor support.Data from an ongoing EGF100161 phase I study evaluating the OTR of lapatinib + docetaxel + trastuzumab shows that the association of lapatinib 1250 mg with docetaxel 75mg/m² is haematological toxic and has recently been amended to evaluate lapatinib 1250 mg with docetaxel 75 mg/m² with systematic growth factor support.A phase I/II EORTC study evaluating docetaxel plus lapatinib in neoadjuvant breast cancer patients has just started. The phase I part of this study will evaluate several lapatinib and docetaxel dose levels before conducting phase II.

The phase I part will enrol patients (in cohorts of 3 or 6) to determine in a step-wise approach, the OTR of lapatinib and docetaxel. Patients should not be entered at a higher dose level until all patients in the previous cohort complete the first cycle of treatment, this first cycle is used to determine OTR. Dose modification of lapatinib will be based on any observed toxicity in the treatment period. The OTR will be defined as the dose level at which £ 1 of 6 patients experiences the DLT (dose limiting toxicity).If no DLT is observed in the first 3 patients at a particular dose level during the first cycle (3 week treatment period), recruitment will start at the next dose levelIf 1/3 patients experiences a DLT at a particular dose level, additional 3 patients will be enrolled at that dose level to a total of 6 patients if no DLT occurred againIf 1/6 patients experiences a DLT at a particular dose level, recruitment will start at the next dose levelIf ³ 2/6 patients experiences the same DLT at a particular dose level, the dose level is not considered to be tolerableIf ³ 2/6 patients experiences two distinct DLT at a particular dose level, additional 3 patients will be enrolled at that dose level to a total of 9 patients. If one of the previously described DLT occurred again among the new enrolled patients, the dose level is not considered to be tolerableA total of 12 patients will be treated at the OTR.The OTR is defined as the dose level at which no more than 1 of 6 patients experiences a DLT.The DLT for this study is defined during cycle 1 for the dose escalation step as:· any grade 3-4 non hematological toxicity as defined by the Common Toxicity Criteria, version 3 (with the exclusion of alopecia, nausea, vomiting, diarrhea, infusion related that can be rapidly controlled with appropriate measures)· an absolute neutrophil count (ANC) \< 0.5x109 /L lasting for \> = 7 day· febrile neutropenia defined as ANC \< 1.0 x109 /L and fever at least 38.5°C· thrombocytopenia \< 25, 000/µl or thrombocytopenic bleeding requiring transfusion· grade 3 or higher left ventricular cardiac dysfunction or a ≥ 20% decrease from baseline in left ventricular ejection fraction (LVEF) that is also below the institution's lower limit of normal (LLN), and confirmed by a repeat evaluation 1 to 2 weeks following the first evaluation.

Lapatinib in Combination With Docetaxel in Patients With HER-2 Positive Advanced or Metastatic Breast Cancer

A Multicenter Open-label, Phase I/II Dose Escalation Study of Oral Lapatinib in Combination With Docetaxel in Patients With HER-2 Positive Advanced or Metastatic Breast Cancer

GlaxoSmithKline

Sanofi

Centre Georges Francois Leclerc

Blood and Lymph Conditions

Immune System Diseases

Symptoms and General Pathology

Leukemia

Lymphoma, Large B-Cell, Diffuse

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma

Leukemia, Lymphocytic, Chronic, B-Cell

Lymphoma, Mantle-Cell

Lymphoma, Follicular

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hematologic Diseases

Lymphoma, B-Cell

Lymphoma, Non-Hodgkin

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Diffuse Large B-Cell Lymphoma

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Chronic Graft Versus Host Disease

Lymphosarcoma

Chronic Lymphocytic Leukemia

Mantle Cell Lymphoma

Follicular Lymphoma

Acute Graft Versus Host Disease

B-cell Lymphoma

Tin Fluorides

During accelerated dose titration in Group 1, participant will receive duvortuxizumab starting at 0.5 nanogram per kilogram (ng/kg) for biweekly dosing. Dose will be increased by half logarithmic steps in subsequent Dose Level (DL). After safety stopping criteria are met, Dose Escalation (DE) in Group 1 will transition to 3+3 design, and will continue until the Maximum tolerated Dose (MTD) is defined. DE in Groups 2 and 3 will follow 3+3 design, begin after initial dose level in Group 1 is deemed safe and recommended phase 2 doses (RP2D) for Part 1 of study can be decided. Duvortuxizumab at a starting dose of 50 ng/kg weekly will also be investigated in Group 1 and will follow 3+3 study design continue until the MTD or Maximum administered dose (MAD) is reached. Disease-specific dose escalation in Group 2 and 3 will not be initiated until dose in Group 1 is determined safe.

Participants with Diffuse-Large B-Cell Lymphoma (DLBCL) will receive intravenous infusion of duvortuxizumab at the recommended Phase 2 dose (RP2D) either with or without a priming dose.

Participants with Follicular Cell Lymphoma (FL) will receive intravenous infusion of duvortuxizumab at the recommended Phase 2 dose (RP2D) either with or without a priming dose.

Participants with Mantle Cell Lymphoma (MCL) will receive intravenous infusion of duvortuxizumab at the recommended Phase 2 dose (RP2D) either with or without a priming dose.

Participants with Chronic Lymphocytic Leukemia (CLL) will receive intravenous infusion of duvortuxizumab at the recommended Phase 2 dose (RP2D) either with or without a priming dose.

Participants with Acute Lymphoblastic Leukemia (ALL) will receive intravenous infusion of duvortuxizumab at the recommended Phase 2 dose (RP2D) either with or without a priming dose.

Participants currently enrolled in the study will continue to receive duvortuxizumab every 14 days (biweekly dosing) in each 28 -day cycle as an intravenous infusion. In the priming dose regimen, a priming dose will be administered on Day 1 followed by full doses on Day 8 and Day 22, of a 35-day Cycle 1, and then every 14 days in each subsequent 28-day cycle. The cohorts will be opened where participants will receive duvortuxizumab every 7 days (for investigating weekly dosing schedule) in each 28-day cycle as an intravenous infusion. In the priming dose regimen, a priming dose will be administered on Day 1 followed by full doses on Day 8, Day 15, Day 22, and Day 28 of a 35-day Cycle 1, and then every 7 days in each subsequent 28-day cycle.

Part 1 (Dose Escalation): Duvortuxizumab

Participants will receive intravenous infusion of duvortuxizumab at the recommended Phase 2 dose (RP2D) defined in Part 1 for their disease type either with or without a priming dose.

Part 2 (Dose Expansion): Duvortuxizumab

Janssen Research & Development, LLC Clinical Trial

The purpose of this study is to evaluate the safety, tolerability, dose-limiting toxicities (any harmful effect of a drug) (DLT), maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D) and preliminary clinical activity of duvortuxizumab when administered intravenously to participants with relapsed or refractory B-cell malignancies \[diffuse-large B cell lymphoma (DLBCL), follicular lymphoma (FL), mantle-cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), and acute lymphoblastic leukemia (ALL)\].

This first in human study consists of 2 parts: a) The dose escalation part and b) The dose expansion part. This is an openlabel (all participants know the identity of the intervention), multicenter (more than one study site) study to evaluate the safety, establish a recommended Phase 2 dose (RP2D), and to determine the preliminary efficacy of duvortuxizumab in participants with relapsed or refractory B cell malignancies. The dose escalation part of the trial (Part 1) will be comprised of 3 different patient groups based on disease indication: Group 1 (DLBCL, FL, MCL); Group 2 (CLL); Group 3 (ALL). The duvortuxizumab dosing will be done on biweekly and weekly basis. Duvortuxizumab weekly escalating dosing will be investigated. Dose escalation will begin with Group 1 and will initially follow an accelerated dose titration design, followed by a traditional 3+3 design. At each dose escalation level the treatment of the second participant should be initiated after at least 72 hours of observation after the start of the first duvortuxizumab dose of the first participant. Dose escalation in Groups 2 and 3 will follow a 3+3 design and will begin after the initial dose level in Group 1 is deemed safe. Participants \[Group 1 (DLBCL, FL, MCL), Group 2 (CLL) Group 3 (ALL)\] are enrolled into cohorts of increasing dose levels of duvortuxizumab administered in 28 day treatment cycles. Up to 3 RP2Ds may be determined in Part 1 (one RP2D for Group 1, one RP2D for Group 2, and one RP2D for Group 3). In the cohort expansion part of the trial (Part 2), participants with relapsed or refractory B cell malignancies (DLBCL, FL, MCL, CLL and ALL) will be enrolled according to tumor type in up to 5 cohorts and receive duvortuxizumab at the RP2D determined in Part 1 for their disease type. The study consists of 3 periods: Screening period (up to 28 days prior to the first dose of study drug); Treatment period \[first dose of study drug until the End of Treatment Visit (within 30 days after the last dose)\]; and follow up period \[End of Treatment Visit and continue until death, lost to follow up, consent withdrawal, or study end (as determined by the sponsor), whichever occurs first\]. Number of participants who achieve an overall response in each Dose Expansion cohort will be evaluated primarily. Participants' safety will be monitored throughout the study.

A Dose Escalation Study of Duvortuxizumab in Participants With Relapsed or Refractory B-cell Malignancies

A Phase 1, First-in-Human, Open-Label, Dose Escalation Study of Duvortuxizumab, A Humanized CD19 x CD3 Dual-Affinity Re-Targeting (DART®) Protein in Subjects With Relapsed or Refractory B-cell Malignancies

The RP2D will be determined based on safety, clinical activity, pharmacokinetics, and pharmacodynamics in participants with relapsed or refractory B cell malignancies \[diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL) and acute lymphoblastic leukemia (ALL)\].

The ORR is defined as the percentage of participants who achieve complete response (CR) or partial response (PR) per criteria for response assessment of Non Hodgkin Lymphomas (NHL) or International Workshop on Chronic Lymphocytic Leukemia (IWCLL), or complete response (CR), complete response with partial hematologic recovery (CRp), or complete response with incomplete recovery of counts (CRi) per response criteria for acute lymphoblastic leukemia (ALL).

The AUC tau is the area under the serum concentration versus time curve during a dose interval time period (tau).

The Cmax is the maximum observed serum concentration of duvortuxizumab.

The t(1/2) is defined as 0.693/Lambda (z)

The CL is a quantitative measure of the rate at which a drug substance is removed from the body.

The Vss is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of duvortuxizumab at steady state.

Plasma levels of antibodies to duvortuxizumab for evaluation of potential immunogenicity.

The DoR is defined as the time from the first observed response (CR or PR) to documented disease progression or death due to any cause.

The PFS is defined as the time from date of the first dose of study drug to documented disease progression or death due to any cause.

The CR is defined as a best response of CR according to the Criteria for Response Assessment of Non-Hodgkin Lymphomas (NHL), International Workshop on Chronic Lymphocytic Leukemia (CLL) or Response Criteria for acute lymphoblastic leukemia (ALL).

Overall survival is defined as the duration from the date of the first dose of the study drug to the date of death for DLBCL, FL, MCL, CLL, and ALL.

An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

Relapse free survival (RFS) is defined as time from the date of the first dose of the study drug to relapse from CR, progressive disease, or death due to any cause for ALL.

Janssen Research & Development, LLC

Digestive System Diseases

Gland and Hormone Related Diseases

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Gastrointestinal Agents

Gemcitabine

Capecitabine

Pancrelipase

Pancreatin

Vandetanib 100mg/day plus Gemcitabine plus CapecitabineDose

Vandetanib 300mg/day plus Gemcitabine plus CapectiabineDose

Vandetanib

Clinical Sciences & Operations

The purpose of this study is to define th Maximum Tolerated Dose (MTD) and the recommended dose (RD) of ZD6474 in combination with a fixed standard dose of gemcitabine and capecitabine

Dose Escalation Study With Zactima and Chemotherapy in Metastatic Pancreas Carcinoma

Dose Escalation Study of the Combination of ZD6474, Gemcitabine and Capecitabine in Locally Advanced Unresectable or Metastatic Pancreatic Adenocarcinoma

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Safety Study of Seneca Valley Virus in Patients With Solid Tumors With Neuroendocrine Features	NCT00314925	Carcinoid Neuroendocrine	Seneca Valley V...	18 Years -	Neotropix
Lapatinib in Combination With Docetaxel in Patients With HER-2 Positive Advanced or Metastatic Breast Cancer	NCT01044485	Metastatic Brea...	lapatinib docetaxel	18 Years -	Centre Georges Francois Leclerc
A Dose Escalation Study of Duvortuxizumab in Participants With Relapsed or Refractory B-cell Malignancies	NCT02454270	Leukemia, Lymph... Lymphoma, Large... Lymphoma, Folli... Lymphoma, Mantl... Precursor Cell ...	Part 1 (Dose Es... Part 2 (Dose Ex...	18 Years -	Janssen Research & Development, LLC
Safety Study of Seneca Valley Virus in Patients With Solid Tumors With Neuroendocrine Features	NCT00314925	Carcinoid Neuroendocrine	Seneca Valley V...	18 Years -	Neotropix
Dose Escalation Study With Zactima and Chemotherapy in Metastatic Pancreas Carcinoma	NCT00681798	Pancreatic Canc...	Vandetanib	18 Years -	Sanofi
Lapatinib in Combination With Docetaxel in Patients With HER-2 Positive Advanced or Metastatic Breast Cancer	NCT01044485	Metastatic Brea...	lapatinib docetaxel	18 Years -	Centre Georges Francois Leclerc

Spots Global Cancer Trial Database for dose escalation study