Proton Beam Radiation Therapy and Chemotherapy in Treating Patients With Stage III Non-Small Cell Lung Cancer That Can Be Removed By Surgery

• Sponsor: Abramson Cancer Center of the University of Pennsylvania (Other)
• Overall Status: Completed
• CT.gov ID: NCT01076231
• Collaborator: (none)
• Enrollment: 34
• Location: 1
• Arm: 1
• Duration (Months): 100.7
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Stage IIIA Non-small Cell Lung Cancer	Radiation: proton beam radiation therapy; Drug: cisplatin; Drug: etoposide; Procedure: therapeutic conventional surgery	Phase 1/Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. 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:

1. 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

1. 1. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 34 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Feasibility and PhaseI/II Trial of Preoperative Proton Beam Radiotherapy With Concurrent Chemotherapy for Resectable Stage IIIA or Superior Sulcus NSCLC
• Study Start Date: Jan 1, 2010
• Actual Primary Completion Date: Dec 1, 2016
• Actual Study Completion Date: May 24, 2018

Arms and Interventions

Arm

Intervention/Treatment

Experimental: 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.

Radiation: proton beam radiation therapy; Drug: cisplatin; Given IV; Other Names: CACP CDDP CPDD DDP Neoplatin PDD ; Drug: etoposide; Given IV; Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside EPEG epipodophyllotoxin VePesid VP-16 VP-16-213 ; Procedure: therapeutic conventional surgery

Outcome Measures

Primary Outcome Measures

1. Number of Participants Deemed Feasible to Receive Intervention [90 Days]

   Feasibility will be based on multiple radiation planning and treatment parameters. Study will be deemed feasible if all patients are deemed feasible.

2. Dose-limiting Toxicity [90 Days]

   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.

3. Late Toxicity [4.5 Years]

   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.

Secondary Outcome Measures

1. Pathologic CR Rate [90 days]

   Pathologic CR rate is defined as the fraction of patients who undergo surgery and have no evidence of disease based on surgical pathology.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion

• Histologically confirmed diagnosis of NSCLC

• Stage IIIA or Potentially resectable superior sulcus tumors

• No evidence of distant metastatic disease as documented by MRI of the brain and PET/CT

• Patients must have a Karnofsky Performance Status of >= 60

• Patients must be able to provide informed consent

• WBC >= 4000/mm^3

• Platelets >= 100,000 mm^3

• Creatinine =< 1.2 mg/dl (urinary diversion is permitted to improve renal function)

• Patients must have bilirubin =< 1.5 mg/dl

• Women of child-bearing potential as long as she agrees to use a recognized method of birth control (e.g. oral contraceptive, IUD, condoms or other barrier methods etc.); hysterectomy or menopause must be clinically documented

• Negative pregnancy test for women of child-bearing age

Exclusion

• Prior or simultaneous malignancies within the past two years (other than cutaneous squamous or basal cell carcinoma, melanoma in situ or thyroid carcinoma) [For pts that will be on definitive treatment study, otherwise delete for umbrella recurrent protocol]

• Pregnant women, women planning to become pregnant and women that are nursing

• Actively being treated on any other research study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Abramson Cancer Center of The University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• Abramson Cancer Center of the University of Pennsylvania

Investigators

• Principal Investigator: Jacob Shabason, MD, Abramson Cancer Center of the University of Pennsylvania

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Abramson Cancer Center of the University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT01076231
• Other Study ID Numbers: UPCC 25508; NCI-2010-00251
• First Posted: Feb 26, 2010
• Last Update Posted: May 17, 2021
• Last Verified: Apr 1, 2021

• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Etoposide; Etoposide phosphate; Podophyllotoxin

Study Results

Participant Flow

Arm/Group Title	Arm I
Arm/Group Description	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
Period Title: Overall Study
STARTED	34
COMPLETED	0
NOT COMPLETED	34

Baseline Characteristics

Arm/Group Title	Arm I
Arm/Group Description	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
Overall Participants	34
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	15 44.1%
>=65 years	19 55.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.88 (9.73)
Sex: Female, Male (Count of Participants)
Female	16 47.1%
Male	18 52.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	2 5.9%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 5.9%
White	30 88.2%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	34 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Deemed Feasible to Receive Intervention
Description	Feasibility will be based on multiple radiation planning and treatment parameters. Study will be deemed feasible if all patients are deemed feasible.
Time Frame	90 Days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I
Arm/Group Description	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
Measure Participants	21
Count of Participants [Participants]	21 61.8%

2. Primary Outcome

Title	Dose-limiting Toxicity
Description	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.
Time Frame	90 Days

Outcome Measure Data

Analysis Population Description

19 patients underwent surgery

Arm/Group Title	Arm I
Arm/Group Description	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
Measure Participants	19
Count of Participants [Participants]	0 0%

3. Primary Outcome

Title	Late Toxicity
Description	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.
Time Frame	4.5 Years

Outcome Measure Data

Analysis Population Description

19 patients underwent surgery

Arm/Group Title	Arm I
Arm/Group Description	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
Measure Participants	19
Count of Participants [Participants]	0 0%

4. Secondary Outcome

Title	Pathologic CR Rate
Description	Pathologic CR rate is defined as the fraction of patients who undergo surgery and have no evidence of disease based on surgical pathology.
Time Frame	90 days

Outcome Measure Data

Analysis Population Description

19 patients underwent surgery

Arm/Group Title	Arm I
Arm/Group Description	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
Measure Participants	19
Number [complete response rate percentage]	21

Adverse Events

Time Frame	90 days
Arm/Group Title	Arm I
Arm/Group Description	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
All Cause Mortality
	Arm I
	Affected / at Risk (%)	# Events
Total	0/34 (0%)
Serious Adverse Events
	Arm I
	Affected / at Risk (%)	# Events
Total	7/34 (20.6%)
Investigations
Lymphocyte count decreased	1/34 (2.9%)
White blood cell decreased	1/34 (2.9%)
Metabolism and nutrition disorders
	5/34 (14.7%)
Other (Not Including Serious) Adverse Events
	Arm I
	Affected / at Risk (%)	# Events
Total	21/34 (61.8%)
Blood and lymphatic system disorders
Anemia	6/34 (17.6%)
Gastrointestinal disorders
	12/34 (35.3%)
Constipation	9/34 (26.5%)
Dyspepsia	4/34 (11.8%)
Dysphagia	4/34 (11.8%)
Esophageal pain	3/34 (8.8%)
Esophagitis	7/34 (20.6%)
Gastroesophageal reflux disease	4/34 (11.8%)
Nausea	5/34 (14.7%)
General disorders
Fatigue	10/34 (29.4%)
Injury, poisoning and procedural complications
Dermatitis radiation	7/34 (20.6%)
Investigations
Lymphocyte count decreased	6/34 (17.6%)
Platelet count decreased	5/34 (14.7%)
White blood cell decreased	6/34 (17.6%)
Metabolism and nutrition disorders
Anorexia	4/34 (11.8%)
Hyperglycemia	4/34 (11.8%)
Hypocalcemia	3/34 (8.8%)
Hyponatremia	5/34 (14.7%)
Nervous system disorders
Headache	4/34 (11.8%)
Psychiatric disorders
Insomnia	3/34 (8.8%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	4/34 (11.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.