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| Name | Class |
|---|---|
| Chinese Academy of Medical Sciences | OTHER |
| Peking University Cancer Hospital & Institute | OTHER |
| Hebei Fourth Hospital | UNKNOWN |
| Jiangsu Cancer Institute & Hospital |
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The purpose of this study is to determine whether the treatment of locally advanced esophageal squamous cell carcinoma (ESCC)with cetuximab in combination with paclitaxel, cisplatin and radiation improve clinical outcomes.
Esophageal cancer is the sixth leading cause of cancer death worldwide.
Over the past 2 decades, well-designed clinical trials have documented the clinical benefits of combination of chemotherapy and radiation for localized esophageal cancer, either as primary therapy or in neoadjuvant setting.
Paclitaxel, a radiation sensitizer, has important single-agent activity in esophageal cancer. Paclitaxel-based chemoradiation has been the framework for the recent Radiation Therapy Oncology Group (RTOG) trials of nonoperative management of esophageal cancer.
Accumulating clinical evidence suggests that epidermal growth factor receptor (EGFR) represents a viable target in the treatment of esophageal cancer. EGFR expression is associated with poor prognosis. Cetuximab, a monoclonal antibody, binds specifically to EGFR on both normal and tumor cells and competitively inhibits the binding of EGF and other ligands, such as transforming growth factor (TGF)-α.
Preclinical models have suggested synergy between cetuximab, paclitaxel, cisplatin and radiation. For patients with locally advanced head and neck cancer, the combination of cetuximab and radiation has demonstrated both response and survival benefit.
With all these, the investigators hypothesize that treatment of locally advanced esophageal squamous cell carcinoma (ESCC)with cetuximab in combination with paclitaxel, cisplatin and radiation may further improve clinical outcomes. This trial results will be important as it may support further studies for setting the new treatment standard for ESCC.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| cetuximab, concurrent chemo-radiotherapy | Experimental | Cetuximab, injection, loading dose400 mg/m^2,(Day1 in Week1) followed by 250 mg/m^2(Day1, every week for Weeks 2-8) Paclitaxel, injection,45 mg/m^2 (Day 1, every week for Weeks 2-8) Cisplatin, injection,20 mg/m^2 (Day 1, every week for Weeks 2-8) radiation therapy, 59.4 Gy, 1.8 Gy/33 fractions,1 fraction daily, Days 1-5 every week for Weeks 2-7, and Days 1-3 for Week 8 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| cetuximab (Erbitux) | Drug | Cetuximab,injection,loading dose400 mg/m^2,(Day1 in Week1) followed by 250 mg/m^2(Day1, every week for Weeks 2-8) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Overall Response Rate (RR) | The overall response rate was defined as the numbers of patients with a complete response (CR) or partial response (PR). CR was defined as no target lesion at follow-up computed tomography scan and barium swallow examination 3-6 weeks after completion of chemo-radiation. PR was defined at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | 1 to 3 month after therapy |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Toxicity | All patients were regularly monitored for possible adverse events, which were graded according to National Cancer Institute Common Toxicity Criteria version 3.0. | Every week during treatment and 1 month after therapy |
| Participants With Overall Survival (OS) at 1 Year |
Not provided
Inclusion Criteria:
Inpatients or outpatients, ≥ 18 years of age
Histologically confirmed primary (non-recurrent) ESCC fulfilling one of the following criteria (AJCC Staging System)
Evidence of unidimensional measurable disease as per Response Evaluation Criteria in Solid Tumours (RECIST).
ECOG Performance status of 0-1
Effective contraception for both male and female patients if the risk of conception exists
Adequate bone marrow reserves: neutrophil (ANC) count ≥ 1500 /mm^3, platelet count ≥ 100,000 /mm^3, hemoglobin ≥ 9 g/dl
Adequate renal function: serum creatinine ≤ 1.5 mg/dl and/or calculated creatinine clearance ≥ 60 ml/min
Adequate hepatic function: bilirubin level ≤ 1.5 x ULN, ASAT & ALST ≤ 1.5 x ULN
Tumor tissue available for KRAS biomarker test
Signed written informed consent prior to study entry
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jin Ming Yu, PH.D, M.D | Shandong Cancer Hospital and Institute | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Radiation Oncology, Shandong Cancer Hospital and Institute | Jinan | Shandong | 250117 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 11208820 | Result | Urba SG, Orringer MB, Turrisi A, Iannettoni M, Forastiere A, Strawderman M. Randomized trial of preoperative chemoradiation versus surgery alone in patients with locoregional esophageal carcinoma. J Clin Oncol. 2001 Jan 15;19(2):305-13. doi: 10.1200/JCO.2001.19.2.305. | |
| 9869669 | Result | Kelsen DP, Ginsberg R, Pajak TF, Sheahan DG, Gunderson L, Mortimer J, Estes N, Haller DG, Ajani J, Kocha W, Minsky BD, Roth JA. Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer. N Engl J Med. 1998 Dec 31;339(27):1979-84. doi: 10.1056/NEJM199812313392704. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Cetuximab, Concurrent Chemo-radiotherapy | Cetuximab, injection, loading dose400 mg/m^2,(Day1 in Week1) followed by 250 mg/m^2(Day1, every week for Weeks 2-8) Paclitaxel, injection,45 mg/m^2 (Day 1, every week for Weeks 2-8) Cisplatin, injection,20 mg/m^2 (Day 1, every week for Weeks 2-8) radiation therapy, 59.4 Gy, 1.8 Gy/33 fractions,1 fraction daily, Days 1-5 every week for Weeks 2-7, and Days 1-3 for Week 8 |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Cetuximab, Concurrent Chemo-radiotherapy | Cetuximab, injection, loading dose400 mg/m^2,(Day1 in Week1) followed by 250 mg/m^2(Day1, every week for Weeks 2-8) Paclitaxel, injection,45 mg/m^2 (Day 1, every week for Weeks 2-8) Cisplatin, injection,20 mg/m^2 (Day 1, every week for Weeks 2-8) radiation therapy, 59.4 Gy, 1.8 Gy/33 fractions,1 fraction daily, Days 1-5 every week for Weeks 2-7, and Days 1-3 for Week 8 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Overall Response Rate (RR) | The overall response rate was defined as the numbers of patients with a complete response (CR) or partial response (PR). CR was defined as no target lesion at follow-up computed tomography scan and barium swallow examination 3-6 weeks after completion of chemo-radiation. PR was defined at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | Posted | Number | participants | 1 to 3 month after therapy |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cetuximab, Concurrent Chemo-radiotherapy | Cetuximab, injection, loading dose400 mg/m^2,(Day1 in Week1) followed by 250 mg/m^2(Day1, every week for Weeks 2-8) Paclitaxel, injection,45 mg/m^2 (Day 1, every week for Weeks 2-8) Cisplatin, injection,20 mg/m^2 (Day 1, every week for Weeks 2-8) radiation therapy, 59.4 Gy, 1.8 Gy/33 fractions,1 fraction daily, Days 1-5 every week for Weeks 2-7, and Days 1-3 for Week 8 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| esophago-tracheal fistula | Injury, poisoning and procedural complications | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hepatic Functional Lesion | Hepatobiliary disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jinming Yu | Shandong Cancer Hospital and Institute | 86-531-87984729 | jn7984729@public.jn.sd.cn |
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| ID | Term |
|---|---|
| D004938 | Esophageal Neoplasms |
| ID | Term |
|---|---|
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D000068818 | Cetuximab |
| D017239 | Paclitaxel |
| D002945 | Cisplatin |
| D011827 | Radiation |
| D020266 | Radiotherapy, Conformal |
| D050397 | Radiotherapy, Intensity-Modulated |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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| OTHER |
| RenJi Hospital | OTHER |
| Zhengzhou University | OTHER |
| West China Hospital | OTHER |
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|
| Paclitaxel | Drug | Paclitaxel,injection,loading dose 45 mg/m^2,(Day1 in every week for Weeks 2-8) |
|
| Cisplatin | Drug | Cisplatin,injection,loading dose 20 mg/m^2,(Day1 in every week for Weeks 2-8) |
|
| Radiation | Radiation | Radiation, External beam therapy, total 59.4 Gy , 33 fractions, 1.8 Gy per fraction.(Day 1-Day 5 in every week 2-week 8). |
|
|
| 1 year from the date of diagnosis |
| Participants With Overall Survival (OS) at 3 Year | 3 year from the date of diagnosis |
| Participants With Progression Free Survival (PFS) | Recurrence or metastasis from the date of diagnosis |
| Number of Participants With K-ras Gene Mutation | DNA was extracted from tumor specimens.Screened for the presence of KRAS codon 12 and 13 mutations using a PCR clamping and melting curve technique. PCR amplification of the wild-type KRAS sequence was suppressed in this process by the incorporation in the reaction mix of a locked nucleic-acid oligomer16 spanning codons 12 and 13 of the KRAS gene. Post-PCR hybridization and melting curve analysis using fluorescently tagged oligonucleotides incorporated in the original PCR reaction permitted the identification and discrimination of distinct KRAS codon 12 and 13 missense mutations. | 07/29/2010-09/30/2010 |
| 9219702 | Result | Bosset JF, Gignoux M, Triboulet JP, Tiret E, Mantion G, Elias D, Lozach P, Ollier JC, Pavy JJ, Mercier M, Sahmoud T. Chemoradiotherapy followed by surgery compared with surgery alone in squamous-cell cancer of the esophagus. N Engl J Med. 1997 Jul 17;337(3):161-7. doi: 10.1056/NEJM199707173370304. |
| 8672151 | Result | Walsh TN, Noonan N, Hollywood D, Kelly A, Keeling N, Hennessy TP. A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med. 1996 Aug 15;335(7):462-7. doi: 10.1056/NEJM199608153350702. |
| 1584260 | Result | Herskovic A, Martz K, al-Sarraf M, Leichman L, Brindle J, Vaitkevicius V, Cooper J, Byhardt R, Davis L, Emami B. Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. N Engl J Med. 1992 Jun 11;326(24):1593-8. doi: 10.1056/NEJM199206113262403. |
| 15142632 | Result | Raben D, Helfrich B, Bunn PA Jr. Targeted therapies for non-small-cell lung cancer: biology, rationale, and preclinical results from a radiation oncology perspective. Int J Radiat Oncol Biol Phys. 2004;59(2 Suppl):27-38. doi: 10.1016/j.ijrobp.2004.01.054. |
| 14967461 | Result | Langer CJ. Emerging role of epidermal growth factor receptor inhibition in therapy for advanced malignancy: focus on NSCLC. Int J Radiat Oncol Biol Phys. 2004 Mar 1;58(3):991-1002. doi: 10.1016/j.ijrobp.2003.09.099. |
| 16467544 | Result | Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, Jones CU, Sur R, Raben D, Jassem J, Ove R, Kies MS, Baselga J, Youssoufian H, Amellal N, Rowinsky EK, Ang KK. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006 Feb 9;354(6):567-78. doi: 10.1056/NEJMoa053422. |
| Participants |
|
| Age Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| Secondary | Number of Participants With Toxicity | All patients were regularly monitored for possible adverse events, which were graded according to National Cancer Institute Common Toxicity Criteria version 3.0. | Posted | Number | participants | Every week during treatment and 1 month after therapy |
|
|
|
| Secondary | Participants With Overall Survival (OS) at 1 Year | Not Posted | Aug 2011 | Number | participants | 1 year from the date of diagnosis |
| Secondary | Participants With Overall Survival (OS) at 3 Year | Not Posted | Aug 2013 | Number | participants | 3 year from the date of diagnosis |
| Secondary | Participants With Progression Free Survival (PFS) | Not Posted | Aug 2013 | Number | participants | Recurrence or metastasis from the date of diagnosis |
| Secondary | Number of Participants With K-ras Gene Mutation | DNA was extracted from tumor specimens.Screened for the presence of KRAS codon 12 and 13 mutations using a PCR clamping and melting curve technique. PCR amplification of the wild-type KRAS sequence was suppressed in this process by the incorporation in the reaction mix of a locked nucleic-acid oligomer16 spanning codons 12 and 13 of the KRAS gene. Post-PCR hybridization and melting curve analysis using fluorescently tagged oligonucleotides incorporated in the original PCR reaction permitted the identification and discrimination of distinct KRAS codon 12 and 13 missense mutations. | Posted | Number | participants | 07/29/2010-09/30/2010 |
|
|
|
| 2 |
| 55 |
| 38 |
| 55 |
| Pneumonia | Infections and infestations | Systematic Assessment |
|
| Granulocytopenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Skin Eruption | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| granlopenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| radiodematitis | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| mucositis | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| radioacitvity esophagitis | Injury, poisoning and procedural complications | Systematic Assessment |
|
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| D006258 |
| Head and Neck Neoplasms |
| D004066 | Digestive System Diseases |
| D004935 | Esophageal Diseases |
| D005767 | Gastrointestinal Diseases |
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017672 | Nitrogen Compounds |
| D017671 | Platinum Compounds |
| D055585 | Physical Phenomena |
| D011881 | Radiotherapy, Computer-Assisted |
| D011878 | Radiotherapy |
| D013812 | Therapeutics |