PAINT: PET-Adjusted Intensity Modulated Radiation Therapy and Combination Chemotherapy in Treating Patients With Stage II-IV Non-small Cell Lung Cancer

• Sponsor: Albert Einstein College of Medicine (Other)
• Overall Status: Completed
• CT.gov ID: NCT02073968
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 35
• Locations: 2
• Arm: 1
• Actual Duration (Months): 88
• Patients Per Site: 17.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This phase II trial studies how well intensity modulated radiation therapy adjusted by positron emission tomography (PET) scanning together with combination chemotherapy works in treating patients with stage II-IV non-small cell lung cancer (NSCLC). Radiation therapy uses high energy x rays to kill tumor cells. In intensity-modulated radiotherapy, multiple beam angles and dozens of beam segments are used to deliver highly conformal radiation therapy. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving PET-adjusted IMRT together with combination chemotherapy may kill more tumor cells.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Malignant Neoplasm in the Brain; Recurrent Non-Small Cell Lung Carcinoma; Stage IIA Non-Small Cell Lung Carcinoma; Stage IIB Non-Small Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer	Drug: Carboplatin; Procedure: Computed Tomography; Radiation: Intensity-Modulated Radiation Therapy; Drug: Paclitaxel; Procedure: Positron Emission Tomography; Radiation: Proton Beam Radiation Therapy	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To estimate the efficacy (based on post-treatment PET findings) of dose-painted intensity-modulated radiotherapy (IMRT) with concurrent chemotherapy for locally-advanced non-small cell lung cancer (LA-NSCLC).

SECONDARY OBJECTIVES:

1. To estimate the efficacy (based on clinical endpoints including locoregional control [LRC], disease-free survival [DFS], and overall survival [OS]) of dose-painted IMRT with concurrent chemotherapy for LA-NSCLC.

2. To evaluate the safety of dose-painted IMRT with concurrent and adjuvant chemotherapy for LA-NSCLC.

3. To evaluate the utility of post-treatment PET/computed tomography (CT) imaging as a predictor of clinical outcomes following treatment with this novel approach.

4. To explore, in a preliminary manner, whether metabolomic markers in the blood and urine prior to and during the course of treatment are associated with treatment response, clinical endpoints, and treatment-related adverse events such as radiation pneumonitis.

OUTLINE:

RADIATION THERAPY: Patients undergo PET-adjusted IMRT or proton beam radiation therapy five days a week for 5 weeks.

CONCURRENT CHEMOTHERAPY: Patients receive carboplatin intravenously (IV) over 3 hours and paclitaxel IV over 1 hour once weekly for 5 weeks beginning week 1 of thoracic radiotherapy.

CONSOLIDATION CHEMOTHERAPY: Beginning approximately 4-6 weeks after the completion of all radiation therapy and when esophagitis and chemotherapy-induced neuropathy are grade 1 or less, absolute neutrophil count (ANC) > 1500, and platelet count > 100,000, patients may receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Treatment may repeat every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity at the discretion of the treating physicians.

After completion of study treatment, patients are followed up at 12-16 weeks, 19 weeks, every 3 months for 2 years, and then every 6 months for a total of 5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 35 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: PET-Adjusted IMRT for NSCLC Trial (PAINT)
• Actual Study Start Date: Jul 1, 2013
• Actual Primary Completion Date: Dec 1, 2017
• Actual Study Completion Date: Nov 1, 2020

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (PET-adjusted IMRT, carboplatin, paclitaxel) RADIOTHERAPY: Patients undergo PET-adjusted IMRT or proton beam radiation therapy five days a week for 5 weeks. CONCURRENT CHEMOTHERAPY: Patients receive carboplatin IV over 3 hours and paclitaxel IV over 1 hour once weekly for 6 weeks beginning week 1 of thoracic radiotherapy. CONSOLIDATION CHEMOTHERAPY: Beginning approximately 4-6 weeks after the completion of all radiation therapy and when esophagitis and chemotherapy-induced neuropathy are grade 1 or less, ANC > 1500, and platelet count > 100,000, patients may receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Treatment may repeat every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity at the discretion of the treating physicians.

Drug: Carboplatin; Given IV; Other Names: Blastocarb Carboplat Carboplatin Hexal Carboplatino Carbosin Carbosol Carbotec CBDCA Displata Ercar JM-8 Nealorin Novoplatinum Paraplat Paraplatin Paraplatin AQ Paraplatine Platinwas Ribocarbo ; Procedure: Computed Tomography; Undergo PET-adjusted IMRT; Other Names: CAT CAT Scan Computerized Axial Tomography Computerized Tomography CT CT SCAN tomography ; Radiation: Intensity-Modulated Radiation Therapy; Undergo PET-adjusted IMRT; Other Names: IMRT Intensity Modulated RT Intensity-Modulated Radiotherapy ; Drug: Paclitaxel; Given IV; Other Names: Anzatax Asotax Bristaxol Praxel Taxol Taxol Konzentrat ; Procedure: Positron Emission Tomography; Undergo PET-adjusted IMRT; Other Names: Medical Imaging, Positron Emission Tomography PET PET SCAN Positron Emission Tomography Scan Positron-Emission Tomography proton magnetic resonance spectroscopic imaging ; Radiation: Proton Beam Radiation Therapy; Undergo proton beam radiation therapy

Outcome Measures

Primary Outcome Measures

1. Metabolic Response of All Pulmonary Lesions and Thoracic Lymph Nodes [Up to 16 weeks after completion of radiation therapy]

   Favorable response will be defined as having maximum SUV less than 6.0 on post-treatment PET/CT.

Secondary Outcome Measures

1. Incidence of Grade >= 2 Radiation-induced Lung Toxicity, Scored Using Common Terminology Criteria for Adverse Events (CTCAE), Version (v.) 4 [Up to 5 years]

   The safety parameters will be presented as frequency and percentages.

2. Incidence of Grade >= 3 Treatment-related Toxicity, Scored Using CTCAE, v. 4 [Up to 5 years]

   The safety parameters will be presented as frequency and percentages.

3. Locoregional Progression-free Survival Assessed Using the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria [From study registration to date of local or regional disease progression or death, censored at the date of data collection, assessed up to 5 years]

   Kaplan-Meier survival plots will be produced. The survival probabilities will be presented. Log-rank testing will be used to compare the survival probabilities between categorical predictors. A Cox regression model will be used to estimate the hazard rates for progression free survival among the predictor variables.

4. Lung Cancer Cause-specific Survival [From study registration to death directly from lung cancer, censored at the date of data collection, assessed up to 5 years]

   A patient will be considered to have died from lung cancer if he or she had evidence of disease progression at any site and no direct evidence of other cause of death. Kaplan-Meier survival plots will be produced.

5. Overall Survival [From study registration to death, censored at the date of data collection, assessed up to 5 years]

   Kaplan-Meier survival plots will be produced. The survival probabilities will be presented. Log-rank testing will be used to compare the survival probabilities between categorical predictors. A Cox regression model will be used to estimate the hazard rates for overall survival among the predictor variables.

6. Progression-free Survival Assessed Using the RECIST Criteria [From study registration to date of disease progression or death, censored at the date of data collection, assessed up to 5 years]

   Kaplan-Meier survival plots will be produced. The survival probabilities will be presented. Log-rank testing will be used to compare the survival probabilities between categorical predictors. A Cox regression model will be used to estimate the hazard rates for progression free survival among the predictor variables.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Pathologically proven (either histologic or cytologic) diagnosis of NSCLC with any of the following stages (according to the American Joint Committee on Cancer [AJCC]

Staging Manual, 7th edition):

• Stage IIIA or IIIB

• Stage II NSCLC with medical contraindication to curative surgical resection

• Stage IV disease with solitary brain metastasis that has been treated radically (eg: with surgical resection or stereotactic radiosurgery) and thoracic disease that would be classified as stage II-III

• Appropriate diagnostic/staging workup, including:

• Complete history and physical examination

• Whole body PET/computed tomography (CT) scan within 42 days prior to study entry demonstrating hypermetabolic pulmonary lesion(s) and/or thoracic lymph node(s), with a maximum standardized uptake volume (SUV) > 6 for at least one lesion; if PET/CT was obtained more than 42 days prior to study entry and is not repeated, CT scan of the chest within 28 days prior to study entry demonstrating stable disease is required

• Magnetic resonance imaging (MRI) of the brain or CT scan of the head with contrast within 42 days prior to study entry

• Biopsy confirmation of suspected metastatic disease identified by PET/CT is recommended

• Pulmonary function tests (PFTs) within 6 weeks of study entry are highly recommended but not required

• No prior chemotherapy or thoracic radiotherapy for lung cancer

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

• Absolute neutrophil count (ANC) >= 1,500 cells/ul

• Platelets >= 100,000 cells/ul

• Hemoglobin >= 9.0 g/dl (Note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 9.0 g/dl is acceptable)

• Total bilirubin < 3.0 times the institutional upper limit of normal (ULN)

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3.0 x the ULN

• Serum creatinine =< 1.5 x ULN or calculated creatinine clearance >= 50 ml/min (by Cockroft-Gault formula)

• Women of childbearing potential must:

• Have a negative serum or urine pregnancy test within 72 hours prior to the start of study therapy

• Agree to utilize an adequate method of contraception throughout treatment and for at least 4 weeks after study therapy is completed

• Be advised of the importance of avoiding pregnancy during trial participation and the potential risks of an unintentional pregnancy

• All patients must sign study specific informed consent prior to study entry

Exclusion Criteria:

• Pleural or pericardial effusion

• A patient with pleural effusion may be enrolled the effusion is sampled by thoracentesis and cytology is negative or the effusion is seen on axial imaging but not on chest x-ray and deemed too small to tap under CT or ultrasound guidance

• Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness

• Women who

• Are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 4 weeks after cessation of study therapy

• Have a positive pregnancy test at baseline

• Are pregnant or breastfeeding

• Poorly controlled diabetes (defined as fasting glucose level > 200 mg/dL) despite attempts to improve glucose control by fasting duration and adjustment of medications; patients with diabetes will preferably be scheduled for PET/CT imaging in the morning, and instructions for fasting and use of medications will be provided in consultation with the patients' primary physicians

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Albert Einstein College of Medicine	Bronx	New York	United States	10461
2	Montefiore Medical Center - Moses Campus	Bronx	New York	United States	10467-2490

Sponsors and Collaborators

• Albert Einstein College of Medicine
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Nitin Ohri, Albert Einstein College of Medicine

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 16, 2017

More Information

Publications

None provided.

• Responsible Party: Nitin Ohri, Principal Investigator, Albert Einstein College of Medicine
• ClinicalTrials.gov Identifier: NCT02073968
• Other Study ID Numbers: 2013-252; NCI-2014-00216; 2013-252; P30CA013330
• First Posted: Feb 28, 2014
• Last Update Posted: Jan 27, 2022
• Last Verified: Jan 1, 2022

• Studies a U.S. FDA-regulated Device Product: Yes
• Additional relevant MeSH terms: Carcinoma; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Neoplasms; Paclitaxel; Carboplatin; Albumin-Bound Paclitaxel

Study Results

Participant Flow

Arm/Group Title	Treatment (PET-adjusted IMRT, Carboplatin, Paclitaxel)
Arm/Group Description	RADIOTHERAPY: Patients undergo PET-adjusted IMRT five days a week for 5 weeks. CONCURRENT CHEMOTHERAPY: Patients receive carboplatin paclitaxel weekly for 5 weeks during thoracic radiotherapy. OPTIONAL CONSOLIDATION CHEMOTHERAPY: Beginning approximately 4-6 weeks after the completion of radiotherapy, subjects may receive up to 3 cycles of consolidation carboplatin and paclitaxel.
Period Title: Overall Study
STARTED	35
COMPLETED	35
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment (PET-adjusted IMRT, Carboplatin, Paclitaxel)
Arm/Group Description	RADIOTHERAPY: Patients undergo PET-adjusted IMRT five days a week for 5 weeks. CONCURRENT CHEMOTHERAPY: Patients receive carboplatin IV over 3 hours and paclitaxel IV over 1 hour once weekly for 6 weeks beginning week 1 of thoracic radiotherapy. CONSOLIDATION CHEMOTHERAPY: Beginning approximately 4-6 weeks after the completion of all radiation therapy and when esophagitis and chemotherapy-induced neuropathy are grade 1 or less, ANC > 1500, and platelet count > 100,000, patients may receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Treatment may repeat every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity at the discretion of the treating physicians. Carboplatin: Given IV Intensity-Modulated Radiation Therapy: Undergo PET-adjusted IMRT Paclitaxel: Given IV Positron Emission Tomography: Undergo PET-adjusted IMRT
Overall Participants	35
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	68
Sex: Female, Male (Count of Participants)
Female	16 45.7%
Male	19 54.3%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (participants) [Number]
United States	35 100%

Outcome Measures

1. Primary Outcome

Title	Metabolic Response of All Pulmonary Lesions and Thoracic Lymph Nodes
Description	Favorable response will be defined as having maximum SUV less than 6.0 on post-treatment PET/CT.
Time Frame	Up to 16 weeks after completion of radiation therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (PET-adjusted IMRT, Carboplatin, Paclitaxel)
Arm/Group Description	RADIOTHERAPY: Patients undergo PET-adjusted IMRT or proton beam radiation therapy five days a week for 5 weeks. CONCURRENT CHEMOTHERAPY: Patients receive carboplatin IV over 3 hours and paclitaxel IV over 1 hour once weekly for 6 weeks beginning week 1 of thoracic radiotherapy. CONSOLIDATION CHEMOTHERAPY: Beginning approximately 4-6 weeks after the completion of all radiation therapy patients may receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Treatment may repeat every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity at the discretion of the treating physicians. Carboplatin: Given IV Intensity-Modulated Radiation Therapy: Undergo PET-adjusted IMRT Paclitaxel: Given IV Positron Emission Tomography: Undergo PET-adjusted IMRT
Measure Participants	30
Count of Participants [Participants]	24 68.6%

2. Secondary Outcome

Title	Incidence of Grade >= 2 Radiation-induced Lung Toxicity, Scored Using Common Terminology Criteria for Adverse Events (CTCAE), Version (v.) 4
Description	The safety parameters will be presented as frequency and percentages.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Incidence of Grade >= 3 Treatment-related Toxicity, Scored Using CTCAE, v. 4
Description	The safety parameters will be presented as frequency and percentages.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Locoregional Progression-free Survival Assessed Using the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria
Description	Kaplan-Meier survival plots will be produced. The survival probabilities will be presented. Log-rank testing will be used to compare the survival probabilities between categorical predictors. A Cox regression model will be used to estimate the hazard rates for progression free survival among the predictor variables.
Time Frame	From study registration to date of local or regional disease progression or death, censored at the date of data collection, assessed up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Lung Cancer Cause-specific Survival
Description	A patient will be considered to have died from lung cancer if he or she had evidence of disease progression at any site and no direct evidence of other cause of death. Kaplan-Meier survival plots will be produced.
Time Frame	From study registration to death directly from lung cancer, censored at the date of data collection, assessed up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Overall Survival
Description	Kaplan-Meier survival plots will be produced. The survival probabilities will be presented. Log-rank testing will be used to compare the survival probabilities between categorical predictors. A Cox regression model will be used to estimate the hazard rates for overall survival among the predictor variables.
Time Frame	From study registration to death, censored at the date of data collection, assessed up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Progression-free Survival Assessed Using the RECIST Criteria
Description	Kaplan-Meier survival plots will be produced. The survival probabilities will be presented. Log-rank testing will be used to compare the survival probabilities between categorical predictors. A Cox regression model will be used to estimate the hazard rates for progression free survival among the predictor variables.
Time Frame	From study registration to date of disease progression or death, censored at the date of data collection, assessed up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Median follow-up time is 5.5 months for the entire cohort and 23.8 months for surviving patients.
Adverse Event Reporting Description	Adverse events were scored using Common Terminology Criteria for Adverse Events version 4.0 at each study visit. Adverse events occurring within 90 days of radiation therapy completion were categorized as acute toxicities, and subsequent adverse events were categorized as late toxicities.
Arm/Group Title	Treatment (PET-adjusted IMRT, Carboplatin, Paclitaxel)
Arm/Group Description	RADIOTHERAPY: Patients undergo PET-adjusted IMRT or proton beam radiation therapy five days a week for 5 weeks. CONCURRENT CHEMOTHERAPY: Patients receive carboplatin IV over 3 hours and paclitaxel IV over 1 hour once weekly for 6 weeks beginning week 1 of thoracic radiotherapy. CONSOLIDATION CHEMOTHERAPY: Beginning approximately 4-6 weeks after the completion of all radiation therapy, patients may receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Treatment may repeat every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity at the discretion of the treating physicians. Carboplatin: Given IV Intensity-Modulated Radiation Therapy: Undergo PET-adjusted IMRT Paclitaxel: Given IV Positron Emission Tomography: Undergo PET-adjusted IMRT
All Cause Mortality
	Treatment (PET-adjusted IMRT, Carboplatin, Paclitaxel)
	Affected / at Risk (%)	# Events
Total	11/35 (31.4%)
Serious Adverse Events
	Treatment (PET-adjusted IMRT, Carboplatin, Paclitaxel)
	Affected / at Risk (%)	# Events
Total	15/35 (42.9%)
Gastrointestinal disorders
Dysphagia	2/35 (5.7%)	2
Nausea	2/35 (5.7%)	2
General disorders
Fatigue	2/35 (5.7%)	2
Metabolism and nutrition disorders
Dehydration	4/35 (11.4%)	4
Respiratory, thoracic and mediastinal disorders
Pneumonitis	2/35 (5.7%)	2
Cough	1/35 (2.9%)	1
Skin and subcutaneous tissue disorders
Dermatitis	2/35 (5.7%)	2
Other (Not Including Serious) Adverse Events
	Treatment (PET-adjusted IMRT, Carboplatin, Paclitaxel)
	Affected / at Risk (%)	# Events
Total	35/35 (100%)
Gastrointestinal disorders
Anorexia	14/35 (40%)	14
Constipation	8/35 (22.9%)	8
Dysphagia	24/35 (68.6%)	24
Respiratory, thoracic and mediastinal disorders
Cough	25/35 (71.4%)	25
Skin and subcutaneous tissue disorders
Dermatitis	19/35 (54.3%)	19

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.