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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2010-00251 |
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RATIONALE: Specialized radiation therapy, such as proton beam radiation therapy, that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue in patients with non-small cell lung cancer. Drugs used in chemotherapy, such as cisplatin and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving proton beam radiation therapy together with combination chemotherapy may kill more tumor cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of proton beam radiation therapy when given together with cisplatin and etoposide and to see how well it works in treating patients with stage III non-small cell lung cancer that can be removed by surgery.
PRIMARY OBJECTIVES:
I. To assess feasibility. (Phase I) II. To determine dose-limiting toxicity and maximum tolerated dose. (Phase I) III. To determine the pathologic CR rate. (Phase II)
SECONDARY OBJECTIVES:
I. To assess late complications from irradiation using proton beam therapy in place of conventional photon beam therapy. (Phase II) II. To assess acute side effects from irradiation using proton beam therapy in place of conventional photon beam therapy. (Phase II) III. To compare the dose distribution to tumor and surrounding normal structures using DVH's (Dose Volume Histograms) generated from the proton plan used to treat the patient and the photon plan generated for comparison purposes. (Phase II) IV. To determine progression-free survival (Phase II) and late toxicity.
OUTLINE: This is a phase I, dose-escalation study of proton beam radiation therapy followed by a phase II study.
Patients undergo proton beam radiotherapy over 5.5-7.5 weeks. Patients receive concurrent chemotherapy comprising cisplatin IV on days 1, 8, 29, and 36 and etoposide IV on days 1-5 and days 29-33.Treatment continues in the absence of disease progression or unacceptable toxicity.
Beginning 4-6 weeks after completion of chemoradiotherapy, patients may undergo surgical resection or additional chemoradiotherapy.
After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 3 years.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm I | Experimental | Patients undergo proton beam radiotherapy over 5.5-7.5 weeks. Patients receive concurrent chemotherapy comprising cisplatin IV on days 1, 8, 29, and 36 and etoposide IV on days 1-5 and days 29-33.Treatment continues in the absence of disease progression or unacceptable toxicity. Beginning 4-6 weeks after completion of chemoradiotherapy, patients may undergo surgical resection or additional chemoradiotherapy. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| proton beam radiation therapy | Radiation |
| ||
| cisplatin |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Deemed Feasible to Receive Intervention | Feasibility will be based on multiple radiation planning and treatment parameters. Study will be deemed feasible if all patients are deemed feasible. | 90 Days |
| Dose-limiting Toxicity | DLT is defined as post-operative mortality (within 30 days of surgery) or any grade 3 or higher pneumonitis or any other grade 4 or higher toxicity which occurs during chemoradiation or within 90 days following the end of treatment, whichever is longer. | 90 Days |
| Late Toxicity | Late toxicity is defined as any grade 3 or higher pneumonitis or any grade 4 or higher toxicity which occurs more than 90 days after surgery or completion of treatment. | 4.5 Years |
| Measure | Description | Time Frame |
|---|---|---|
| Pathologic CR Rate | Pathologic CR rate is defined as the fraction of patients who undergo surgery and have no evidence of disease based on surgical pathology. | 90 days |
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Inclusion
Exclusion
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| Name | Affiliation | Role |
|---|---|---|
| Jacob Shabason, MD | Abramson Cancer Center at Penn Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Abramson Cancer Center of The University of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37201756 | Derived | Simone CB 2nd, Yegya-Raman N, Manjunath S, Verma V, Shabason JE, Xu L, Cengel KA, Levin WP, Berman AT, Christodouleas JP, Aggarwal C, Cohen RB, Langer CJ, Pechet TT, Singhal S, Kucharczuk JC, Rengan R, Feigenberg SJ. Prospective Feasibility and Phase 1/2 Trial of Preoperative Proton Beam Therapy With Concurrent Chemotherapy for Resectable Stage IIIA or Superior Sulcus Non-Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys. 2023 Nov 1;117(3):683-689. doi: 10.1016/j.ijrobp.2023.05.016. Epub 2023 May 17. No abstract available. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm I | Patients undergo proton beam radiotherapy over 5.5-7.5 weeks. Patients receive concurrent chemotherapy comprising cisplatin IV on days 1, 8, 29, and 36 and etoposide IV on days 1-5 and days 29-33.Treatment continues in the absence of disease progression or unacceptable toxicity. Beginning 4-6 weeks after completion of chemoradiotherapy, patients may undergo surgical resection or additional chemoradiotherapy. proton beam radiation therapy cisplatin: Given IV etoposide: Given IV therapeutic conventional surgery |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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Given IV |
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| etoposide | Drug | Given IV |
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| therapeutic conventional surgery | Procedure |
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| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm I | Patients undergo proton beam radiotherapy over 5.5-7.5 weeks. Patients receive concurrent chemotherapy comprising cisplatin IV on days 1, 8, 29, and 36 and etoposide IV on days 1-5 and days 29-33.Treatment continues in the absence of disease progression or unacceptable toxicity. Beginning 4-6 weeks after completion of chemoradiotherapy, patients may undergo surgical resection or additional chemoradiotherapy. proton beam radiation therapy cisplatin: Given IV etoposide: Given IV therapeutic conventional surgery |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||||
| Region of Enrollment | Number | participants |
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| 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 Deemed Feasible to Receive Intervention | Feasibility will be based on multiple radiation planning and treatment parameters. Study will be deemed feasible if all patients are deemed feasible. | Posted | Count of Participants | Participants | 90 Days |
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| Primary | Dose-limiting Toxicity | DLT is defined as post-operative mortality (within 30 days of surgery) or any grade 3 or higher pneumonitis or any other grade 4 or higher toxicity which occurs during chemoradiation or within 90 days following the end of treatment, whichever is longer. | 19 patients underwent surgery | Posted | Count of Participants | Participants | 90 Days |
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| Primary | Late Toxicity | Late toxicity is defined as any grade 3 or higher pneumonitis or any grade 4 or higher toxicity which occurs more than 90 days after surgery or completion of treatment. | 19 patients underwent surgery | Posted | Count of Participants | Participants | 4.5 Years |
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| Secondary | Pathologic CR Rate | Pathologic CR rate is defined as the fraction of patients who undergo surgery and have no evidence of disease based on surgical pathology. | 19 patients underwent surgery | Posted | Number | complete response rate percentage | 90 days |
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90 days
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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 | Arm I | Patients undergo proton beam radiotherapy over 5.5-7.5 weeks. Patients receive concurrent chemotherapy comprising cisplatin IV on days 1, 8, 29, and 36 and etoposide IV on days 1-5 and days 29-33.Treatment continues in the absence of disease progression or unacceptable toxicity. Beginning 4-6 weeks after completion of chemoradiotherapy, patients may undergo surgical resection or additional chemoradiotherapy. proton beam radiation therapy cisplatin: Given IV etoposide: Given IV therapeutic conventional surgery | 0 | 34 | 7 | 34 | 21 | 34 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Metabolism and nutrition disorders | Non-systematic Assessment |
| |||
| Lymphocyte count decreased | Investigations | Non-systematic Assessment |
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| White blood cell decreased | Investigations | Non-systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gastrointestinal disorders | Non-systematic Assessment |
| |||
| Anemia | Blood and lymphatic system disorders | Non-systematic Assessment |
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| Anorexia | Metabolism and nutrition disorders | Non-systematic Assessment |
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| Constipation | Gastrointestinal disorders | Non-systematic Assessment |
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| Dermatitis radiation | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | Non-systematic Assessment |
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| Dysphagia | Gastrointestinal disorders | Non-systematic Assessment |
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| Dyspnea | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Esophageal pain | Gastrointestinal disorders | Non-systematic Assessment |
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| Esophagitis | Gastrointestinal disorders | Non-systematic Assessment |
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| Fatigue | General disorders | Non-systematic Assessment |
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| Gastroesophageal reflux disease | Gastrointestinal disorders | Non-systematic Assessment |
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| Headache | Nervous system disorders | Non-systematic Assessment |
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| Hyperglycemia | Metabolism and nutrition disorders | Non-systematic Assessment |
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| Hypocalcemia | Metabolism and nutrition disorders | Non-systematic Assessment |
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| Hyponatremia | Metabolism and nutrition disorders | Non-systematic Assessment |
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| Insomnia | Psychiatric disorders | Non-systematic Assessment |
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| Lymphocyte count decreased | Investigations | Non-systematic Assessment |
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| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
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| Platelet count decreased | Investigations | Non-systematic Assessment |
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| White blood cell decreased | Investigations | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Jacob Shabason | University of Pennsylvania | 215-662-3998 | susan.mazzoni@uphs.upenn.edu |
| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| D061766 | Proton Therapy |
| D002945 | Cisplatin |
| D005047 | Etoposide |
| D011034 | Podophyllotoxin |
| ID | Term |
|---|---|
| D063193 | Heavy Ion Radiotherapy |
| D011878 | Radiotherapy |
| D013812 | Therapeutics |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017672 | Nitrogen Compounds |
| D017671 | Platinum Compounds |
| D013764 | Tetrahydronaphthalenes |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| D005960 | Glucosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D017705 | Lignans |
| D001593 | Benzyl Compounds |
| D001555 | Benzene Derivatives |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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