Neoplasms

All Conditions

Diseases and Abnormalities at or Before Birth

Skin and Connective Tissue Diseases

Nutritional and Metabolic Diseases

Rare Diseases

Sarcoma

Ichthyosis, X-Linked

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Soft Tissue Sarcoma

Anti-Infective Agents

All Drugs and Chemicals

Anti-Bacterial Agents

Immunomodulating Agents

Cephalosporins

Antibiotics, Antitubercular

First Generation Cephalosporins

Immunologic Factors

Arm A - University of Florida - External Beam Radiation Therapy (RT) - As outlined in Intervention Description

Arm B - Moffitt Cancer Center - External Beam RT + Autologous Dendritic Cells (DC) Injection - As outlined in Intervention Description

Day 1: Start external beam RT, 25 fractions from days 1-33 administered Monday through Friday only (no conventional external beam RT on days 6, 7, 13, 14, 20, 21, 27, or 28

Days 57-70: Surgery will occur 3-5 weeks after the final dose of external beam RT.

Day 78-91: First post-operative visit

Days 91-365: Clinical follow-up

Beyond day 365, follow-up will be conducted using the standard of care approach applicable to these patients for the determination of disease recurrence, progression and survival.

External Beam Radiation Therapy (RT)

Prior to each injection on Arm B, patients may receive prophylactic doses of a first generation cephalosporin antibiotic per physician discretion.

Following each DC injection, Arm B patients will assess procedure-associated pain on a scale of 0-10. The next Monday following each DC injection, the patient will be called and questioned about such procedure associated toxicities.

Autologous Dendritic Cells

Alberto Chiappori, M.D.

Daniel Indelicato, M.D.

The purpose of this study is to determine if injection of the participant's our own immune related white blood cells (called dendritic cells) into their tumor will strengthen their immune system to fight against their cancer.

Radiation Therapy and Intratumoral Autologous Dendritic Cells in Soft Tissue Sarcomas (STS)

A Phase II Study Evaluating Neoadjuvant Administration of High Dose Radiation Therapy and Intratumoral Autologous Dendritic Cells in Patients With High-risk Soft Tissue Sarcomas

Investigate the ability of an intensified radiation therapy (RT) regimen (namely, conventional RT with a high-dose hypofractionated boost) and Dendritic Cell (DC) administration to induce an enhanced T lymphocyte immune response specific for STS-TAAs. Criteria for immune response evaluation: Individual patients were considered as responders to TAAs if at any time point the response in IFN-γ ELISPOT assay was found higher than 30 spots per 200,000 cells or in proliferation assay higher than 3000 counts/min (CPM) AND the response in IFN-γ ELISPOT or proliferation assays to tumor cell lysates (TCL) or Ad-Surv was found more than 2SD higher than the response to corresponding control lysate or Ad-c at the same time point AND 2SD higher than the response to the same stimuli at a base line (before start of the treatment).

Evaluate the safety of intratumoral injections of DCs in combination with an intensified RT regimen patients with high-grade large STS. Toxicity assessments were performed weekly to include assessments for: constitutional symptoms, fever, fatigue; common radiation side effects; special attention was paid to DC injection and biopsy related toxicity. Only treatment related SAEs and AEs are reported for this measure.

University of Florida

H. Lee Moffitt Cancer Center and Research Institute

All adverse events, regardless of causality.

Active Comparator: External Beam Radiation Therapy (RT)

Experimental: External Beam RT + DC Injection

Total

Age, Continuous

Age, Categorical

Sex: Female, Male

United States

Region of Enrollment

Investigators planned to accrue 21 patients in each arm for a total of 42 participants.

Number of Participants With Enhanced T Lymphocyte Immune Response Specific for Soft Tissue Sarcoma Tumor Associated Antigens(STS-TAAs)

Treatment Emergent SAEs

Treatment Emergent Other AEs

Number of Participants With Treatment Emergent Serious Adverse Events (SAEs) and Adverse Events (AEs)

Overall Study

Digestive System Diseases

Esophageal Neoplasms

Adenocarcinoma

Stomach Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Stomach Diseases

Esophageal Cancer

Stomach Cancer

Antineoplastic Agents

Paclitaxel

Albumin-Bound Paclitaxel

Carboplatin

Fluorouracil

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Immunosuppressive Agents

Vandetanib 100 mg (6 patients) or 200 mg (3 patients) orally daily during the conventional 3D-guided conformal radiation therapy plus chemotherapy with carboplatin (AUC 5) on days 1 and 29, paclitaxel 50 mg/m2 i.v. weekly on days 1, 8, 15, 22, 29; and continuous infusion of 5-fluorouracil at 225 mg/m2 for 96 hours Monday-Friday during the radiation.

Vandetanib 100mg orally escalating to doses of 200 mg daily 7 days a week until completion of radiation therapy

Vandetanib

5-FU 225 mg/m2/day continuous infusion over96 hours during radiation therapy

5 Fluorouracil (FU)

Carboplatin AUC=5 days 1 and 29 during radiation therapy

Paclitaxel 50 mg/m2 days 1, 8, 15, 22, 29 during radiation therapy

External Beam Radiation Therapy(XRT)to a total dose of 4,500 centiGray (cGy) (180 cGy fractions daily) Monday through Friday for five weeks

Igor Astsaturov,, M.D., Ph.D.

The purpose of the study is to determine the most tolerable and safe dose of ZD6474 (Zactima, Vandetanib) when given with standard chemotherapy, radiation therapy and surgery in patients with cancer of the esophagus

Epidermal Growth Factor Receptor (EGFR) is known to be an important prognostic factor for patients with esophageal cancer-overexpression is associated with a worse prognosis. Review of the literature demonstrates presence of EGFR expression in up 90% of cases of esophageal cancer. Additionally, Vascular Endothelial Growth factor (VEGF) is commonly overexpressed in esophageal cancer (especially adenocarcinoma) and is linked to the transition from Barrett's esophagus to invasive adenocarcinoma. Esophageal cancers with overexpression of VEGF are associated with a worse prognosis and poorer response to conventional chemoradiation.

Therefore, we feel it would be valuable to add an inhibitor of EGFR and VEGFR to the therapy of esophageal cancer to increase the rate of pathologic complete response and thus improve overall survival. In current trials of ZD6474 in combination with chemotherapy, the dose has been 300mg. We will perform a phase I trial in which we will dose-escalate ZD6474 to determine if this drug is tolerable in combination with cytotoxic chemotherapy and external beam radiation therapy. This would be the first trial in humans in which f these three modalities would be combined. We will determine the maximum tolerated dose of ZD6474 in this small trial and then hope to perform a larger phase II trial, perhaps in the context of the Radiation Therapy Oncology Group (RTOG).

A Trial of ZD6474, Paclitaxel, Carboplatin, 5-Fluorouracil, and Radiation Therapy Followed by Surgery

Induction Therapy for Locally Advanced, Resectable Cancer of the Esophagus, Gastroesophageal (GE) Junction and Gastric Cancer: A Phase I Trial of ZD6474 (Zactima, Vandetanib), Paclitaxel, Carboplatin, 5-Fluorouracil, and Radiation Therapy Followed by Surgery

To determine the maximum tolerated dose (MTD) of Vandetanib given concurrently with chemotherapy and radiation therapy followed by surgery (esophagectomy)evaluated by the frequency, severity and duration of adverse events that occur during treatment and for four weeks following surgery as measured by serial blood tests, electrocardiograms and physical assessments

To determine the safety and tolerability of Vandetanib when given in combination with chemotherapy and radiation therapy as evaluated by serial blood tests, electrocardiograms, and physical assessments during therapy and for four weeks following surgery

AstraZeneca

Fox Chase Cancer Center

Adverse events evaluated for severity and relationship to therapy using a grading system in which Grade 3 = severe, Grade 4 = life-threatening or disabling and Grade 5 = death

All patients were treated with vandetanib with dose escalation from 100 mg (dose level 1) to 200 mg (dose level 2) orally daily for the duration of radiation therapy

Years

Race (NIH/OMB)

Middle third

Lower third

GE junction

Tumor site type

Esophagus

Gastroesophageal junction

Primary Site of Disease

Study closed due to reaching the stated endpoint of determination of the phase II recommended and tolerated dose of Vandetanib

Igor Astsaturov, MD, PhD, Assistant Professor, Medical Oncology

All patients were treated with Vandetanib 100 mg QD (6 patients) or 200 mg daily (3 patients) orally daily during the conventional 3D-guided conformal radiation therapy plus chemotherapy with carboplatin (AUC 5) on days 1 and 29, paclitaxel 50 mg/m2 i.v. weekly on days 1, 8, 15, 22, 29; and continuous infusion of 5-fluorouracil at 225 mg/m2 for 96 hours Monday-Friday during the radiation.

Maximum Tolerated Dose of Vandetanib

All patients were treated with Vandetanib 100 mg QD (6 patients) or 200 mg QD (3 patients) orally daily during the conventional 3D-guided conformal radiation therapy plus chemotherapy with carboplatin (AUC 5) on days 1 and 29, paclitaxel 50 mg/m2 i.v. weekly on days 1, 8, 15, 22, 29; and continuous infusion of 5-fluorouracil at 225 mg/m2 for 96 hours Monday-Friday during the radiation.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Radiation Therapy and Intratumoral Autologous Dendritic Cells in Soft Tissue Sarcomas (STS)	NCT01347034	Soft Tissue Sar...	External Beam R... Autologous Dend...	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
A Trial of ZD6474, Paclitaxel, Carboplatin, 5-Fluorouracil, and Radiation Therapy Followed by Surgery	NCT01183559	Cancer of the E... Adenocarcinoma ... Cancer of the S...	Vandetanib 5 Fluorouracil ... Carboplatin Paclitaxel External Beam R...	18 Years -	Fox Chase Cancer Center
Radiation Therapy and Intratumoral Autologous Dendritic Cells in Soft Tissue Sarcomas (STS)	NCT01347034	Soft Tissue Sar...	External Beam R... Autologous Dend...	18 Years -	H. Lee Moffitt Cancer Center and Research Institute

Spots Global Cancer Trial Database for external beam radiation therapy (rt)