Neoplasms

Gland and Hormone Related Diseases

All Conditions

Thyroid Neoplasms

Thyroid Diseases

Endocrine System Diseases

Endocrine Gland Neoplasms

Head and Neck Neoplasms

Micronutrients

Anti-Infective Agents

All Drugs and Chemicals

Iodine

Cadexomer iodine

Five times of p53 gene intratumoral injection are given before surgery,then radical surgery will be conducted.

pre-surgery p53 gene treatment: 10exp12 virus particles per 3 days for 5 times

rAd-p53 gene

surgery

p53 gene treatment: 10exp12 virus particles per 3 days for 10 times

p53 gene therapy

p53 gene therapy with concurrent radioactive iodine pre-surgery p53 gene treatment: 10exp12 virus particles per 3 days for 10 times

p53 gene therapy with radioactive iodine

aiqi wang, MD

Jingqiang Zhu, PhD, MD

Jingqiang Zhu, MD,PhD

This is multicenter, open-label, randomized, active-controled, phase IV study of local direct intra-tumor injection of rAd-p53 monotherapy, with concurrent radioactive iodine , or combination with surgery for treatment of advanced malignant thyroid tumors.

Primary objectives of this study is to determine the efficacy profiles of rAd-p53 intra-tumor injection alone, with with concurrent radioactive iodine, or combination with surgery for treatment of advanced malignant thyroid tumors(stage III or IV) including target lesion complete response rate (LCR) and overall target lesion response rate (OLR), response duration (RD), and progress-free survival (PFS).

The secondary objectives of this study is to investigate overall response rate (OPCR) and overall complete response rate (OCR), overall survival (OS), ECOG, and safety of rAd-p53 monotherapy and combined with radioactive iodine,or surgery.

rAd-p53 Gene Therapy for Advanced Malignant Thyroid Tumors

Open-Label, Multi-Center, Randomized, Active-Controlled, Phase 4 Study of rAd-p53 Gene Mono-Therapy, With Concurrent Radioactive Iodine , or Combination With Surgery in Subjects With Advanced Malignant Thyroid Tumors

Shenzhen SiBiono GeneTech Co.,Ltd

Respiratory Tract (Lung and Bronchial) Diseases

Digestive System Diseases

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Lung Neoplasms

Carcinoma

Stomach Neoplasms

Breast Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Lymphoma

Urinary Bladder Neoplasms

Melanoma

Carcinoma, Renal Cell

Kidney Neoplasms

Stomach Cancer

Esophageal Cancer

Ovarian Cancer

Ovarian Epithelial Cancer

Lymphosarcoma

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Antineoplastic Agents

Analgesics

Herbal and Botanical

Immunomodulating Agents

Interleukin-2

Cola

Dose escalation (0.015 mg/kg, 0.04 mg/kg, 0.08 mg/kg, 0.12 mg/kg, 0.14 mg/kg, 0.16 mg/kg), intravenous infusions, two treatment cycle, each cycle with 4 daily on-dose infusion, 10 days rest between cycles.

ALT-801

This is a Phase 1, open-labeled, non-randomized, multi-center, competitive enrollment and dose-escalation study of ALT-801, the study drug. The purpose of this study is to evaluate the safety, determine the maximum-tolerated dose (MTD) and characterize the pharmacokinetic profile of ALT-801 in previously treated patients with progressive metastatic malignancies. ALT-801, a recombinant fusion protein with a interleukin-2 (IL-2) component, has a targeting mechanism that recognizes tumor cells with a specific tumor marker.

Most current cancer treatment strategies involve the use of chemotherapeutic or biological drugs that exhibit variable efficacy and considerable toxicity. The limitations are often the result of the adverse side effects of the therapeutic drug on normal tissues. One approach to control these effects is to target the therapy to the tumor site. Of the identified tumor antigens, the human p53 tumor suppressor protein is overexpressed in a wide range of human malignancies. p53 is an intracellular tumor suppressor protein that acts to arrest the proliferation of cells. When mutated, it loses its ability to suppress abnormal proliferation and exhibits a longer half-life than the wild-type protein, allowing for its accumulation in tumors. In addition, p53 overexpression correlates with tumor transformation and aggression and is associated with lower overall survival rates and resistance to chemotherapeutic intervention in cancer patients. Therefore, p53 appears to be a marker for a considerable number of human malignancies and represents a good target for immunotherapeutics. However, p53 cannot be used as a target for antibodies because it is not displayed independently on the cell surface. Instead, the p53 protein is processed intracellularly into peptide fragments that are then displayed on the cell surface in the context of major histocompatibility complex (MHC). These peptide/MHC complexes are recognized by T-cells via their T-cell receptors (TCRs). Recently it has been confirmed that the peptide fragment is significantly elevated in a wide range of human tumor tissues, particularly in melanoma, renal, lung, breast, colorectal, bladder, ovary, stomach, esophagus, lymphoma, liver, leukemia, and head \& neck cancer. Targeted approaches to concentrate therapeutic cytokines at the tumor sites that express p53 could provide considerable advantages over current treatment.

Interleukin-2 (IL-2) is a well-characterized growth factor for immune effector cells which play critical roles in tumor control and rejection. A recombinant human IL-2 has been approved for treating metastatic melanoma and renal cell carcinoma. However, the major drawback of IL-2 therapy is its severe systemic toxicity. As a result, use of high dose IL-2 is limited to specialized programs with experienced personnel and it is generally offered to patients who are responsive and have excellent organ function. Thus, there is a critical need for innovative strategies that enhance the effects of IL-2 or reduce its toxicity without compromising clinical benefits.

The study drug, ALT-801, is a biologic compound composed of interleukin-2 (IL-2) genetically fused to a humanized soluble T-cell receptor directed against the p53-derived antigen. This study is to evaluate whether directing IL-2 activity using ALT-801 to the patient's tumor sites that overexpress p53 results in clinical benefits.

The study drug will be administered by bolus intravenous infusion in an in-patient hospital setting under the supervision of a qualified physician experienced in the use of anti-cancer agents including high dose IL-2. An intensive care facility and specialists skilled in cardiopulmonary or intensive care medicine must be available. There are two treatment cycles. For each treatment cycle, patients will be admitted to the hospital, remain in the hospital during the study drug infusion period, and be discharged from the hospital the day after the last infusion at the Principal Investigator's discretion. There is a 10-day resting period between the treatment cycles. Tumor assessments will be done at weeks 7 and 11 after starting the study drug.

Safety and Efficacy Study of ALT-801 to Treat Progressive Metastatic Malignancies

Phase I Study of ALT-801 in Patients With Progressive Metastatic Malignancies

Number of serious adverse events per cohort

Number of dose limiting toxicities (DLTs). A DLT is a toxicity that results in patient withdrawal from the study as defined in the protocol.

Number of subjects with a complete response (CR), partial response (PR) or stable disease (SD). CR is defined as disappearance of all tumor lesions selected for measurement. PR is defined as at least 30% decrease in the sum of all tumor lesions selected for measurement. Stable disease is defined as neither sufficient tumor shrinkage to qualify for PR nor sufficient tumor increase to qualify for progressive disease (PD) which is defined as at least 20% increase the sum of the all tumor lesions selected for measurement.

Number of tumor-responsive (interferon-gamma positive (IFNg+)) immune cells in blood post dosing

Altor BioScience

ALT-801 0.015 mg/kg/Dose

ALT-801 0.040 mg/kg/Dose

ALT-801 0.080 mg/kg/Dose

Total

Age, Categorical

Age Continuous

Sex: Female, Male

Race (NIH/OMB)

Hing C. Wong, Chief Clinical Officer

The Safety and Toxicity of ALT-801 in Patients With Progressive Metastatic Malignancies

The Maximum-tolerated Dose (MTD) of ALT-801

Clinical Antitumor Response to ALT-801

ALT-801 Induced Cell-mediated Immune Responses

Immunogenicity of ALT-801

ALT-801 0.040 mg/kg/ Dose

Overall Study

chemotherapy plus p53

chemotherapy

radiotherapy

Longjiang Li, PhD

Longjiang Li, Ph.D., M.D

longjiang Li, M.D., Ph. D.

This is multicenter, open-label, randomized, active-controled, phase IV study of local direct intra-tumor injection of rAd-p53 monotherapy, with concurrent chemotherapy , with concurrent radiotherapy, or combination with surgery for treatment of head and neck malignant tumors in advanced stage .

Primary objectives of this study is to determine the efficacy profiles of rAd-p53 intra-tumor injection alone, with concurrent chemotherapy, with concurrent radiotherapy, or combination with surgery for treatment of head and neck malignant tumors in advanced stage (stage III or IV) including target lesion complete response rate (LCR) and overall target lesion response rate (OLR), response duration (RD), and progress-free survival (PFS).

The secondary objectives of this study is to investigate overall response rate (OPCR) and overall complete response rate (OCR), overall survival (OS), ECOG, and safety of rAd-p53 monotherapy and combined with chemotherapy, radiotherapy or surgery.

p53 Gene Therapy for Head and Neck Malignant Tumors in Advanced Stage

Open-Label, Multi-Center, Randomized, Active-Controlled, Phase 4 Study of rAd-p53 Gene Therapy Combined With Chemotherapy and Radiotherapy in Treament of Head and Neck Cancer in Advanced Stage

p53 gene therapy with concurrent chemotherapy

Intra-tumor injectio of rAd-p53 gene with no concurrent treatment

p53 gene with surgery

p53 gene treatment: 10exp12 virus particles per 3 days for 10 times Chemotherapy: standard chemotherapy

p53 with chemotherapy

qing yu, MD

Longjiang Li, PhD, MD

This is multicenter, open-label, randomized, active-controled, phase IV study of local direct intra-tumor injection of rAd-p53 monotherapy, with concurrent chemotherapy , or combination with surgery for treatment of advanced oral and maxillofacial malignant tumors.

Primary objectives of this study is to determine the efficacy profiles of rAd-p53 intra-tumor injection alone, with concurrent chemotherapy, or combination with surgery for treatment of advanced oral and maxillofacial malignant tumors(stage III or IV) including target lesion complete response rate (LCR) and overall target lesion response rate (OLR), response duration (RD), and progress-free survival (PFS).

The secondary objectives of this study is to investigate overall response rate (OPCR) and overall complete response rate (OCR), overall survival (OS), ECOG, and safety of rAd-p53 monotherapy and combined with chemotherapy,or surgery.

rAd-p53 Gene Therapy for Advanced Oral and Maxillofacial Malignant Tumors

Open-Label, Multi-Center, Randomized, Active-Controlled, Phase 4 Study of rAd-p53 Gene Mono-Therapy, With Concurrent Chemotherapy, or Combination With Surgery in Subjects With Advanced Oral and Maxillofacial Malignant Tumors

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Cisplatin

Intravenous infusions; 2 treatment courses; 2 treatment cycles for each course; 70mg/m2 on day 1 of cycle 1 for each course

Intravenous infusions; cycle 1: day 3 and 5; cycle 2: day 1, 3 and 5; nine day rest period between cycles; seven day recovery period between courses

Stage 1: dose escalation (0.04 mg/kg, 0.06 mg/kg, 0.08 mg/kg)

Stage 2: dose expansion (dose at MTD)

Hing Wong, PhD

This is a Phase Ib/II, open-label, multi-center, competitive enrollment and dose-escalation study of ALT-801 combined with cisplatin. The purpose of this study is to evaluate the safety, determine the Maximum-Tolerated Dose (MTD), and characterize the pharmacokinetic profile of ALT-801 given with cisplatin in patients who are chemotherapy naïve and have metastatic melanoma that is considered surgically incurable. The anti-tumor responses of ALT-801 with cisplatin will also be assessed in this trial.

Most current cancer treatment strategies involve the use of chemotherapeutic or biological drugs that exhibit variable efficacy and considerable toxicity. The limitations are often the result of the adverse side effects of the therapeutic drug on normal tissues. One approach to control these effects is to target the therapy to the tumor site. Of the identified tumor antigens, the human p53 tumor suppressor protein is overexpressed in a wide range of human malignancies. p53 is an intracellular tumor suppressor protein that acts to arrest the proliferation of cells. When mutated, it loses its ability to suppress abnormal proliferation and exhibits a longer half-life than the wild-type protein, allowing for its accumulation in tumors. In addition, p53 overexpression correlates with tumor transformation and aggression and is associated with lower overall survival rates and resistance to chemotherapeutic intervention in cancer patients. Therefore, p53 appears to be a marker for a considerable number of human malignancies and represents a good target for immunotherapeutics. However, p53 cannot be used as a target for antibodies because it is not displayed independently on the cell surface. Instead, the p53 protein is processed intracellularly into peptide fragments that are then displayed on the cell surface in the context of MHC. These peptide/MHC complexes are recognized by T-cells via their T-cell receptors (TCRs). Recently it has been confirmed that a p53 peptide fragment is significantly elevated in a wide range of human tumor tissues, particularly in melanoma, renal, lung, breast, colorectal, and osteosarcoma cancers. As a result, the feasibility of using soluble TCRs to target therapies against tumor cells that overexpress p53 is being investigated.

Interleukin-2 (IL-2) is a well-characterized growth factor for immune effector cells which play critical roles in tumor control and rejection. As a result, recombinant human IL-2 (e.g., Proleukin®, Chiron Novartis) has been approved for treatment of metastatic melanoma and renal cell carcinoma. IL-2 treatment provides significant benefit to a subset of patients with some maintaining durable responses for over ten years post-treatment. However, the major drawbacks of IL-2 therapy are its limited half-life and severe systemic toxicity. Hence, the use of high dose IL-2 is limited to specialized programs with experienced personnel, and it is generally offered to patients who are responsive and have excellent organ function. The low dose IL-2 treatment, while less toxic and more convenient, produces lower response rates and appears to be less effective in treating metastatic tumors. Thus, there is a critical need for innovative strategies that enhance the effects of IL-2 or reduce its toxicity without compromising clinical benefit. Targeted approaches to concentrate therapeutic cytokines, such as IL-2, at the tumor sites that express p53 could provide considerable advantages over current treatment.

The study drug, ALT-801, is a biologic compound composed of interleukin-2 (IL-2) genetically fused to a humanized soluble T-cell receptor directed against the p53-derived peptides expressed on tumor cells. This study is to evaluate whether directing IL-2 activity using ALT-801 to the patient's tumor sites that overexpress p53 results in clinical benefits if the ALT-801 treatment is given with cisplatin.

Platinum-based analogues including cisplatin, alone or in combination with other chemotherapies, have been shown to be active in patients with metastatic melanoma. Additionally, it is known that cisplatin, an alkylating agent known to inhibit DNA synthesis of dividing cells, triggers increased intracellular level of p53. The synergistic effects of cisplatin and ALT-801 treatment may induce cisplatin-mediated increases in p53 peptide display on the tumors and subsequently enhance tumor targeting of ALT-801.

QUILT-2.008: Study of ALT-801 With Cisplatin in Patients With Metastatic Melanoma

Phase Ib/II Study of ALT-801 With Cisplatin in Patients With Metastatic Melanoma

National Cancer Institute (NCI)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
rAd-p53 Gene Therapy for Advanced Malignant Thyroid Tumors	NCT00902122	Advanced Malign...	rAd-p53 gene surgery p53 gene therap... p53 gene therap...	18 Years - 85 Years	Shenzhen SiBiono GeneTech Co.,Ltd
Safety and Efficacy Study of ALT-801 to Treat Progressive Metastatic Malignancies	NCT00496860	Progressive Met...	ALT-801	18 Years -	Altor BioScience
p53 Gene Therapy for Head and Neck Malignant Tumors in Advanced Stage	NCT00894153	Neoplasms	chemotherapy pl... chemotherapy radiotherapy	18 Years - 65 Years	Shenzhen SiBiono GeneTech Co.,Ltd
rAd-p53 Gene Therapy for Advanced Oral and Maxillofacial Malignant Tumors	NCT00902083	Advanced Oral a...	p53 gene with s... surgery p53 with chemot... p53 gene therap...	18 Years - 85 Years	Shenzhen SiBiono GeneTech Co.,Ltd
QUILT-2.008: Study of ALT-801 With Cisplatin in Patients With Metastatic Melanoma	NCT01029873	Metastatic Mela...	Cisplatin ALT-801	18 Years -	Altor BioScience
rAd-p53 Gene Therapy for Advanced Oral and Maxillofacial Malignant Tumors	NCT00902083	Advanced Oral a...	p53 gene with s... surgery p53 with chemot... p53 gene therap...	18 Years - 85 Years	Shenzhen SiBiono GeneTech Co.,Ltd
rAd-p53 Gene Therapy for Advanced Malignant Thyroid Tumors	NCT00902122	Advanced Malign...	rAd-p53 gene surgery p53 gene therap... p53 gene therap...	18 Years - 85 Years	Shenzhen SiBiono GeneTech Co.,Ltd

Spots Global Cancer Trial Database for p53 gene

Every month we try and update this database with for p53 gene cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for p53 gene

Every month we try and update this database with for p53 gene cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for p53 gene cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.