Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Albumin-Bound Paclitaxel

Carboplatin

AEG35156 will be given as a 2-hour intravenous infusion once weekly with a 2-hour loading dose given daily in the 2 days immediately prior to Day 1 (on Days -2 and -1) only in Cycle 1.

AEG35156

Robert M Jotte, MD

Jacques Jolivet, MD, FACP

This is an open-label multicenter, phase 1-2 study. Following determination of the recommended AEG35156 dose in combination with carboplatin and paclitaxel in the initial Phase 1 part of this study, additional patients will be enrolled in the Phase 2 part of the study to assess the activity of the combination in advanced non small cell lung cancer.

Apoptotic induction in cancer cells is a sought after therapeutic goal. Most successful anticancer agents activate apoptosis pathways in the cancers they treat. Apoptotic pathways in cells appear to converge on a single family of enzymes, the caspases, which are proteases that dismantle the cell in an orderly, non-inflammatory fashion, resulting in cell death. The X-linked Inhibitor of Apoptosis (XIAP) is the only known cellular inhibitor of caspases, its over expression thereby blocking the principal means of apoptosis. A wide range of evidence indicates that cellular overexpression of members of the IAP family is a fundamental means by which many cancer cells evade death, even in the presence of strong extrinsic (death receptor-mediated) and intrinsic (mitochondria-mediated) apoptotic cues. The inhibition of cellular XIAP activity, specifically in cancer cells under stress and primed for apoptosis by chemotherapeutic agents, is viewed as a powerful means of tipping the balance towards cell death. In particular, XIAP down regulation has been shown to enhance taxane cytotoxicity preclinically. AEG35156 is a second generation antisense which targets XIAP mRNA to lower XIAP levels and the apoptotic threshold of cancer cells, enhancing their sensitivity to intrinsic death and chemotherapy. AEG35156 may thus enhance the anticancer activity of carboplatin and paclitaxel in patients with advanced non small cell lung cancer

A Phase 1-2 XIAP Antisense AEG35156 With Carboplatin and Paclitaxel in Patients With Advanced Non-Small Cell Lung Cancer

A Phase 1-2, Multicenter, Open-Label Study of the X-Linked Inhibitor of Apoptosis (XIAP) Antisense AEG35156 Given in Combination With Carboplatin and Paclitaxel in Patients With Advanced Non-Small Cell Lung Cancer

Aegera Therapeutics

Jacques Jolivet, MD, Senior VP Clinical

Pharmaceutical Solutions

Jacques Jolivet, MD

This study is designed to find the maximum tolerated dose, safety and toxicity profile, and to identify any dose limiting toxicities of AEG35156 administered in 2-hour infusions to patients with advanced cancers.

This is a Phase I study, single-arm, open-label, dose escalation study to establish the recommended dose and activity of AEG35156 administered as a 2-hour daily infusion over 3 days initially followed by weekly 2-hour intravenous infusions in patients with advanced cancers. Subjects eligible for study entry must have proven advanced or metastatic cancer refactory to conventional treatment or for which no conventional therapy exists. The starting dose will be a fixed dose of 60 mg/day with escalation by steps of 50 to 100% in successive cohorts. Approximately of 30 patients will be entered in the study to determine the maximum tolerated dose.

Study of XIAP Antisense for Advanced Cancers

A Phase I Trial of AEG35156 Administered by 2-Hour Intravenous Infusion in Patients With Advanced Cancers

Blood and Lymph Conditions

Rare Diseases

Leukemia

Leukemia, Myelomonocytic, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Leukemia, Myeloid

Acute Graft Versus Host Disease

2 days loading dose followed by weekly 2hr infusion

XIAP antisense

The purpose of this study is to determine if the drug, called AEG35156, can be safely given to AML patients and whether it effectively reduces levels of a protein (XIAP) to increase the sensitivity of cancer cells to chemotherapy (ara-C and idarubicin) in patients with refractory or relapsed AML.

This is a phase I/II, single-arm, open-label, study to establish the recommended dose and activity of AEG35156 administered as a daily x3 two-hour infusion prior to reinduction chemotherapy with idarubicin and ara-C followed by weekly two-hour AEG35156 infusions. Subjects eligible for study entry must have confirmed diagnosis of AML in first relapse after an initial CR that lasted less than 6 months or primary refractory AML. Fixed dose of idarubicin and ara-C will be given, plus one of eight doses of AEG35156: 12, 24, 48, 75, 110, 165, 250 and 350mg/m2. A maximum of 54 patients will be treated in cohorts of size 3, starting at 12mg/m2, and not skipping any untried dose level when escalating. Following dose escalation, approximately 20 patients will be treated at the best acceptable dose as determined by the method of Thall and Cook (2004).

Study of XIAP Antisense Given With Chemotherapy for Refractory/Relapsed AML

An Open-Label Phase I/II Study of XIAP Antisense AEG35156 Administered to Patients With Refractory/Relapsed AML in Combination With Chemotherapy

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Immune System Diseases

Skin and Connective Tissue Diseases

Prostatic Neoplasms

Lymphoma

Melanoma

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Lymphosarcoma

Neuroendocrine Tumor

Neuroepithelioma

PNT2258 is composed of PNT100, a 24-mer oligonucleotide, the active drug substance encapsulated in a liposome.

Patients will receive PNT2258 as an intravenous infusion once daily for 5 consecutive days (Days 1-5) of every 21-day cycle (3 weeks). The treatment cycle repeats every 3 weeks for up to 6 cycles in the absence of disease progression, unacceptable toxicity, or patient withdrawal from the study.

PNT2258

Anthony W Tolcher, MD, FRCP(C)

This study is sponsored by Sierra Oncology, Inc. formerly ProNAi Therapeutics, Inc. The purpose of this research study is to evaluate the safety of the investigational drug PNT2258 in patients with advance tumors and see how it acts in the body.

This study is an open-label, single-arm, Phase 1 dose-escalation study of PNT2258 in patients with advanced solid tumors for which no standard therapy exists. Patients will receive PNT2258 as an intravenous infusion once daily for 5 consecutive days (Days 1-5) of every 21-day cycle (3 weeks). At first, patients will be treated in single patient cohorts following an accelerated titration design and evaluated for toxicities. After the accelerated portion ends, patients will be treated in cohorts of at least 3 patients at each dose level and evaluated for treatment-related toxicities.

A Study of PNT2258 in Patients With Advanced Solid Tumors

A Phase 1 Study of PNT2258 in Patients With Advanced Solid Tumors

Safety and tolerability of PNT2258 and the determination of dose-limiting toxicities (DLTs) and the recommended Phase 2 dose

Sierra Oncology LLC - a GSK company

Symptoms and General Pathology

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Oblimersen

Oblimerson sodium, G3139

This non-randomized study will test the safety and effectiveness of Genasense in patients with CLL.

This study is a two-part phase I-II study. Part 1 will determine the MTD of Genasense in patients with CLL. This dose will then be tested in a non-randomized, multi-center, Phase II sequential clinical trial of Genasense used alone for treatment of patients with advanced CLL.

Pharmacokinetics of Genasense and kinetics of Bcl-2 down regulation and re-expression in CLL cells will be followed in selected patients.

Phase I/II Study of Genasense in Patients With Chronic Lymphocytic Leukemia

Phase I-II Multicenter Study of Genasense (Bcl-2 Antisense Oligonucleotide) in Patients With Advanced Chronic Lymphocytic Leukemia

Genta Incorporated

Antirheumatic Agents

Fludarabine

Fludarabine phosphate

Rituximab

Antineoplastic Agents, Immunological

Immunologic Factors

28-day cycles; Cycle 1: oblimersen by continuous IV infusion 1.5 mg/kg/d for 7 consecutive days, completing on Day 8; rituximab by IV infusion on Day 4 (125 mg/m2) and Day 6 (250 mg/m2); fludarabine 25 mg/m2 by IV infusion for 3 days, starting on Day 6. Subsequent cycles: oblimersen 3 mg/kg/d, completing on Day 8; rituximab 375 mg/m2 on Day 5; fludarabine 25 mg/m2 for 3 days starting the same day as rituximab

Oblimersen-rituximab-fludarabine

The treatment combination of Rituxan® (rituximab) and fludarabine has previously been reported to produce a high percentage of responses with less toxicity than other combination treatments. However, some leukemia subjects continue to have leukemia despite treatment with these standard anticancer drug therapies, or they may work for only a short period of time. In some subjects, when the leukemia does not respond well to therapy the leukemia cells may be over-producing one or more proteins. One of these proteins is called Bcl-2. Bcl-2 is a protein that appears to protect cancer cells from being killed and thus lengthens the life of the cancer cells. Genasense® (oblimersen sodium) is a compound that blocks production of the Bcl-2 protein. By first lowering levels of Bcl-2, it is possible that chemotherapy drugs may work more effectively as a cancer treatment. Genasense® may also directly kill CLL cells. This study will test whether treating subjects with Genasense®, fludarabine and rituximab is safe and effective.

Genasense® (Oblimersen Sodium), Fludarabine, and Rituximab in Subjects With Chronic Lymphocytic Leukemia

A Pilot Study of Genasense® (G3139, Oblimersen Sodium, Bcl-2 Antisense Oligonucleotide), Fludarabine and Rituximab in Previously Treated Subjects With Chronic Lymphocytic Leukemia

Breast Neoplasms

Breast Diseases

AEG35156 will be given as a 2-hour intravenous infusion once weekly only on weeks when paclitaxel is administered, with a 2-hour loading dose given daily in the 2 days immediately prior to Day 1 (on Days -2 and -1) only in Cycle 1.

David M Loesch, MD

This is an open-label multicenter, phase 1-2 study. Following determination of the recommended AEG35156 dose in combination with weekly paclitaxel in the initial Phase 1 part of this study, additional patients will be enrolled in the Phase 2 part of the study to assess the activity of the combination in advanced breast cancer.

Breast cancer is the most common cancer in women in the United States, the second most common cause of cancer death, and the main cause of death in women ages 45 to 55. In 2006, 212,920 American women will be diagnosed with breast cancer, and 40,970 will die from this disease.\[1\]. Fewer than 10 percent of women present with metastatic disease at the time of diagnosis. However, the majority of women who relapse after initial definitive therapy for early stage or locally advanced disease will do so with disseminated metastatic disease rather than an isolated local recurrence. Treatment for metastatic disease is palliative in intent and will usually involve hormone therapy and/or chemotherapy with or without trastuzumab. Active chemotherapy agents include anthracyclines, taxanes, vinorelbine, alkylating agents and antimetabolites. Taxanes have become the cornerstone of first-line treatment for metastatic breast cancer. Weekly doses of paclitaxel can be administered continuously for several weeks with a remarkable lack of myelosuppression \[2\]. Weekly paclitaxel (80 mg/m2) was directly compared to every three-week therapy (175 mg/m2) in 585 women with metastatic breast cancer. Weekly therapy was associated with a significantly higher response rate (40 versus 28 percent) and longer TTP (nine versus five months), but similar overall survival and worse neurotoxicity \[3\]. Since patients with metastatic breast cancer are unlikely to be cured of their disease \[4\], they should be considered candidates for a clinical trial.

A Phase 1-2, XIAP Antisense AEG35156 With Weekly Paclitaxel in Patients With Advanced Breast Cancer

A Phase 1-2, Multicenter, Open-Label Study of the X-Linked Inhibitor of Apoptosis (XIAP) Antisense AEG35156 Given in Combination With Weekly Paclitaxel in Patients With Advanced Breast Cancer

Jacques Jolivet, VP Clinical

Digestive System Diseases

Carcinoma, Hepatocellular

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Hematinics

Liver Extracts

Sorafenib

Protein Kinase Inhibitors

Enzyme Inhibitors

MTL-CEBPA administered weekly, twice weekly or thrice weekly over 3 weeks followed by 1 week of rest defining a 28-day cycle.

MTL-CEBPA is administered weekly or twice weekly in combination with sorafenib over 3 weeks followed by 1 week of rest defining a 28-day cycle.

MTL-CEBPA is administered weekly or twice weekly for 2 cycles (28-day cycle) followed by 2 cycles of sorafenib

MTL-CEBPA

Sorafenib 200mg

Dr Debashis Sarker, MBChB, MRCP

Professor Nagy Habib, FRCS

MNA-3521-011 study is a multi-centre, open-label, first-in-human, phase 1a/b clinical study dose/dose frequency escalation followed by a cohort expansion part. MTL-CEBPA is administered as monotherapy or in combination with sorafenib to patients with advanced hepatocellular carcinoma and cirrhosis of the liver. All participants will be considered unsuitable for liver tumour resection and/or is refractory to radiotherapy and other loco-regional therapies.

MTL-CEBPA consists of a double stranded RNA formulated into a SMARTICLES® liposomal nanoparticle and is designed to activate the CEBPA gene.

First-in-Human Safety, Tolerability and Antitumour Activity Study of MTL-CEBPA in Patients With Advanced Liver Cancer

A First-in-Human, Multi-centre, Open-label, Phase 1a/b Clinical Study With RNA Oligonucleotide Drug MTL-CEBPA to Investigate Its Safety, Tolerability, and Antitumour Activity in Patients With Advanced Liver Cancer

Frequency of adverse events graded according to NCI CTCAE v5.0

Increase or decrease in tumour measurement using Response Evaluation Criteria in Solid Tumours (RECIST) reports

Frequency of treatment-related adverse events graded according to NCI CTCAE v5.0

Mina Alpha Limited

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase 1-2 XIAP Antisense AEG35156 With Carboplatin and Paclitaxel in Patients With Advanced Non-Small Cell Lung Cancer	NCT00558922	Carcinoma, Non-...	AEG35156	18 Years -	Aegera Therapeutics
A Phase 1-2 XIAP Antisense AEG35156 With Carboplatin and Paclitaxel in Patients With Advanced Non-Small Cell Lung Cancer	NCT00558922	Carcinoma, Non-...	AEG35156	18 Years -	Aegera Therapeutics
A Phase 1-2 XIAP Antisense AEG35156 With Carboplatin and Paclitaxel in Patients With Advanced Non-Small Cell Lung Cancer	NCT00558922	Carcinoma, Non-...	AEG35156	18 Years -	Aegera Therapeutics
Study of XIAP Antisense for Advanced Cancers	NCT00385775	Advanced Cancer	AEG35156	18 Years -	Aegera Therapeutics
Study of XIAP Antisense Given With Chemotherapy for Refractory/Relapsed AML	NCT00363974	Leukemia, Myelo...	XIAP antisense	18 Years -	Aegera Therapeutics
A Study of PNT2258 in Patients With Advanced Solid Tumors	NCT01191775	Cancer Lymphoma Prostate Cancer Melanoma	PNT2258	18 Years -	Sierra Oncology LLC - a GSK company
Phase I/II Study of Genasense in Patients With Chronic Lymphocytic Leukemia	NCT00021749	Chronic Lymphoc... CLL	Oblimerson sodi...	18 Years -	Genta Incorporated
Genasense® (Oblimersen Sodium), Fludarabine, and Rituximab in Subjects With Chronic Lymphocytic Leukemia	NCT00078234	Chronic Lymphoc...	Oblimersen-ritu...	18 Years -	Genta Incorporated
A Phase 1-2, XIAP Antisense AEG35156 With Weekly Paclitaxel in Patients With Advanced Breast Cancer	NCT00558545	Human Mammary C...	AEG35156	18 Years -	Aegera Therapeutics
First-in-Human Safety, Tolerability and Antitumour Activity Study of MTL-CEBPA in Patients With Advanced Liver Cancer	NCT02716012	Hepatocellular ... Liver Cancer	MTL-CEBPA Sorafenib 200mg	16 Years -	Mina Alpha Limited
A Study of PNT2258 in Patients With Advanced Solid Tumors	NCT01191775	Cancer Lymphoma Prostate Cancer Melanoma	PNT2258	18 Years -	Sierra Oncology LLC - a GSK company
Phase I/II Study of Genasense in Patients With Chronic Lymphocytic Leukemia	NCT00021749	Chronic Lymphoc... CLL	Oblimerson sodi...	18 Years -	Genta Incorporated
Study of XIAP Antisense for Advanced Cancers	NCT00385775	Advanced Cancer	AEG35156	18 Years -	Aegera Therapeutics

Spots Global Cancer Trial Database for oligonucleotide