Accelerated Hypofractionated Radiation Therapy Immediately Before Surgery in Treating Patients With Malignant Pleural Mesothelioma

• Sponsor: Jonsson Comprehensive Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02672033
• Collaborator: (none)
• Enrollment: 2
• Location: 1
• Arm: 1
• Actual Duration (Months): 34.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This pilot phase 0 trial studies accelerated hypofractionated radiation therapy immediately before surgery in treating patients with malignant pleural mesothelioma (cancer in the thin layer of tissue that covers the lungs and lines the interior wall of the chest cavity). Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Hypofractionated radiation therapy is a type of radiation therapy in which the total prescribed dose of radiation is divided into fewer but larger doses as compared to conventional radiation therapy. Giving accelerated hypofractionated radiation therapy immediately before surgery may improve survival, and may also reduce side effects experienced by patients with pleural mesothelioma.

Condition or Disease	Intervention/Treatment	Phase
Pleural Epithelioid Mesothelioma; Pleural Malignant Mesothelioma	Radiation: Hypofractionated Radiation Therapy; Radiation: Intensity-Modulated Radiation Therapy; Other: Laboratory Biomarker Analysis; Procedure: Therapeutic Conventional Surgery	N/A

Detailed Description

PRIMARY OBJECTIVES:

1. To determine the feasibility and toxicity (both acute and chronic) of accelerated hypofractionated neoadjuvant helical intensity modulated radiation therapy prior to pleurectomy/decortication for malignant pleural mesothelioma.

SECONDARY OBJECTIVES:

1. To determine the pathologic complete response rate (pCR). II. To determine the tumor local control rate (LC). III. To determine the malignant pleural mesothelioma disease specific survival (DSS).

2. To determine the overall survival (OS). V. To assess transforming growth factor beta (TGF-B), interleukin (IL)-1, and IL-6 levels as predictive biomarkers for treatment induced tissue injury.

3. To assess the changes in the postoperative pleural immunological milieu in terms of chemo- and cytokine expression.

OUTLINE:

Patients undergo 5 fractions of accelerated hypofractionated intensity-modulated radiation therapy (IMRT) over 1 week with simultaneous integrated boost to gross disease. Patients then undergo pleurectomy/decortication within 14 days after completion of IMRT.

After completion of study treatment, patients are followed up at 6 weeks, and then every 3 months for 5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Neoadjuvant Accelerated Hypofractionated Radiation Therapy Immediately Prior to Radical Pleurectomy/Decortication for Malignant Pleural Mesothelioma: A Pilot Study
• Actual Study Start Date: Sep 1, 2015
• Actual Primary Completion Date: May 24, 2016
• Actual Study Completion Date: Jul 17, 2018

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (hypofractionated IMRT, pleurectomy/decortication) Patients undergo 5 fractions of accelerated hypofractionated IMRT over 1 week with simultaneous integrated boost to gross disease. Patients then undergo pleurectomy/decortication within 14 days after completion of IMRT.

Radiation: Hypofractionated Radiation Therapy; Undergo accelerated hypofractionated IMRT; Other Names: Hypofractionated Radiotherapy hypofractionation ; Radiation: Intensity-Modulated Radiation Therapy; Undergo accelerated hypofractionated IMRT; Other Names: IMRT Intensity Modulated RT Intensity-Modulated Radiotherapy ; Other: Laboratory Biomarker Analysis; Correlative studies; Procedure: Therapeutic Conventional Surgery; Undergo pleurectomy/decortication

Outcome Measures

Primary Outcome Measures

1. Ability to Accrue Sufficient Patients to Draw Conclusions About Endpoints in a Timely and Expedient Manner [Up to 1 year]

   No data displayed because Outcome Measure has zero total participants analyzed.

2. Incidence of Acute and Subacute Toxicity Defined as Grade 4 or 5 Adverse Events as Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 [Up to 3 months]

   No data displayed because Outcome Measure has zero total participants analyzed.

3. Incidence of Chronic Toxicity as Assessed by the NCI CTCAE Version 4.0 [Up to 5 years post-treatment]

   No data displayed because Outcome Measure has zero total participants analyzed.

Secondary Outcome Measures

1. Disease Specific Survival (DSS) [Up to 5 years post-treatment]

   Cumulative incidence approach will be used to estimate DSS. No data displayed because Outcome Measure has zero total participants analyzed.

2. Local Control (LC) [Up to 5 years post-treatment]

   Cumulative incidence approach will be used to estimate the local failure rates. No data displayed because Outcome Measure has zero total participants analyzed.

3. Overall Survival (OS) [Up to 5 years post-treatment]

   No data displayed because Outcome Measure has zero total participants analyzed.

4. Pathologic Complete Response Rate (pCR) [Up to 5 years post-treatment]

   No data displayed because Outcome Measure has zero total participants analyzed.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically confirmed epithelioid predominantly (> 70%) subtype malignant pleural mesothelioma

• Patient must have been evaluated by a University of California Los Angeles (UCLA) thoracic surgeon, and deemed medically and technically suitable for a pleurectomy/decortication procedure

• Karnofsky performance status (KPS) >= 70 or Eastern Cooperative Oncology Group (ECOG) 0-2

• If a woman is of childbearing potential, a negative urine or serum pregnancy test must be documented; women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; or abstinence) for duration of study participation and for up to 4 weeks following the study

Exclusion Criteria:

• Patients who have previously received therapeutic radiation therapy to the chest

• Active systemic, pulmonary, or pericardial infection

• Use of chemotherapy within 4 weeks of the planned start of radiation therapy

• Pregnant women, or women of childbearing potential who are sexually active and not willing/able to use medically acceptable forms of contraception for the entire study period and for up to 4 weeks after the study

• Refusal to sign the informed consent

• Patients who are participating in a concurrent treatment protocol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA / Jonsson Comprehensive Cancer Center	Los Angeles	California	United States	90095

Sponsors and Collaborators

• Jonsson Comprehensive Cancer Center

Investigators

• Principal Investigator: Percy Lee, UCLA / Jonsson Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jonsson Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT02672033
• Other Study ID Numbers: 15-000487; NCI-2015-01736; JCCCID552; 15-000487
• First Posted: Feb 3, 2016
• Last Update Posted: Jul 24, 2020
• Last Verified: May 1, 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Additional relevant MeSH terms: Mesothelioma; Mesothelioma, Malignant

Study Results

Participant Flow

Recruitment Details	From 10/2015 to 04/2018, 2 subjects were consented into the trial.
Pre-assignment Detail	Eligibility screening by the Jonsson Comprehensive Cancer Center Data Safety Monitoring Board. Subjects undergo 5 fractions of hypofractionationated Intensity Modulated Radiation Therapy (IMRT) over 1 week with simultaneous integrated boost to gross disease.Subjects then undergo pleurectomy/decortication within 14 days after completion of IMRT.

Arm/Group Title	Treatment (Hypofractionated IMRT, Pleurectomy/Decortication)
Arm/Group Description	Patients undergo 5 fractions of accelerated hypofractionated IMRT over 1 week with simultaneous integrated boost to gross disease. Patients then undergo pleurectomy/decortication within 14 days after completion of IMRT. Hypofractionated Radiation Therapy: Undergo accelerated hypofractionated IMRT Intensity-Modulated Radiation Therapy: Undergo accelerated hypofractionated IMRT Laboratory Biomarker Analysis: Correlative studies Therapeutic Conventional Surgery: Undergo pleurectomy/decortication
Period Title: Overall Study
STARTED	2
COMPLETED	2
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment (Hypofractionated IMRT, Pleurectomy/Decortication)
Arm/Group Description	Patients undergo 5 fractions of accelerated hypofractionated IMRT over 1 week with simultaneous integrated boost to gross disease. Patients then undergo pleurectomy/decortication within 14 days after completion of IMRT. Hypofractionated Radiation Therapy: Undergo accelerated hypofractionated IMRT Intensity-Modulated Radiation Therapy: Undergo accelerated hypofractionated IMRT Laboratory Biomarker Analysis: Correlative studies Therapeutic Conventional Surgery: Undergo pleurectomy/decortication
Overall Participants	2
Age, Customized (Count of Participants)
63 Years	1 50%
69 Years	1 50%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	2 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	2 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	2 100%

Outcome Measures

1. Primary Outcome

Title	Ability to Accrue Sufficient Patients to Draw Conclusions About Endpoints in a Timely and Expedient Manner
Description	No data displayed because Outcome Measure has zero total participants analyzed.
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

Data was not collected

Arm/Group Title	Treatment (Hypofractionated IMRT, Pleurectomy/Decortication)
Arm/Group Description	Patients undergo 5 fractions of accelerated hypofractionated IMRT over 1 week with simultaneous integrated boost to gross disease. Patients then undergo pleurectomy/decortication within 14 days after completion of IMRT. Hypofractionated Radiation Therapy: Undergo accelerated hypofractionated IMRT Intensity-Modulated Radiation Therapy: Undergo accelerated hypofractionated IMRT Laboratory Biomarker Analysis: Correlative studies Therapeutic Conventional Surgery: Undergo pleurectomy/decortication
Measure Participants	0

2. Primary Outcome

Title	Incidence of Acute and Subacute Toxicity Defined as Grade 4 or 5 Adverse Events as Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
Description	No data displayed because Outcome Measure has zero total participants analyzed.
Time Frame	Up to 3 months

Outcome Measure Data

Analysis Population Description

Data was not collected

Arm/Group Title	Treatment (Hypofractionated IMRT, Pleurectomy/Decortication)
Arm/Group Description	Patients undergo 5 fractions of accelerated hypofractionated IMRT over 1 week with simultaneous integrated boost to gross disease. Patients then undergo pleurectomy/decortication within 14 days after completion of IMRT. Hypofractionated Radiation Therapy: Undergo accelerated hypofractionated IMRT Intensity-Modulated Radiation Therapy: Undergo accelerated hypofractionated IMRT Laboratory Biomarker Analysis: Correlative studies Therapeutic Conventional Surgery: Undergo pleurectomy/decortication
Measure Participants	0

3. Primary Outcome

Title	Incidence of Chronic Toxicity as Assessed by the NCI CTCAE Version 4.0
Description	No data displayed because Outcome Measure has zero total participants analyzed.
Time Frame	Up to 5 years post-treatment

Outcome Measure Data

Analysis Population Description

Data was not collected

Arm/Group Title	Treatment (Hypofractionated IMRT, Pleurectomy/Decortication)
Arm/Group Description	Patients undergo 5 fractions of accelerated hypofractionated IMRT over 1 week with simultaneous integrated boost to gross disease. Patients then undergo pleurectomy/decortication within 14 days after completion of IMRT. Hypofractionated Radiation Therapy: Undergo accelerated hypofractionated IMRT Intensity-Modulated Radiation Therapy: Undergo accelerated hypofractionated IMRT Laboratory Biomarker Analysis: Correlative studies Therapeutic Conventional Surgery: Undergo pleurectomy/decortication
Measure Participants	0

4. Secondary Outcome

Title	Disease Specific Survival (DSS)
Description	Cumulative incidence approach will be used to estimate DSS. No data displayed because Outcome Measure has zero total participants analyzed.
Time Frame	Up to 5 years post-treatment

Outcome Measure Data

Analysis Population Description

No data was collected

Arm/Group Title	Treatment (Hypofractionated IMRT, Pleurectomy/Decortication)
Arm/Group Description	Patients undergo 5 fractions of accelerated hypofractionated IMRT over 1 week with simultaneous integrated boost to gross disease. Patients then undergo pleurectomy/decortication within 14 days after completion of IMRT. Hypofractionated Radiation Therapy: Undergo accelerated hypofractionated IMRT Intensity-Modulated Radiation Therapy: Undergo accelerated hypofractionated IMRT Laboratory Biomarker Analysis: Correlative studies Therapeutic Conventional Surgery: Undergo pleurectomy/decortication
Measure Participants	0

5. Secondary Outcome

Title	Local Control (LC)
Description	Cumulative incidence approach will be used to estimate the local failure rates. No data displayed because Outcome Measure has zero total participants analyzed.
Time Frame	Up to 5 years post-treatment

Outcome Measure Data

Analysis Population Description

No data was collected

Arm/Group Title	Treatment (Hypofractionated IMRT, Pleurectomy/Decortication)
Arm/Group Description	Patients undergo 5 fractions of accelerated hypofractionated IMRT over 1 week with simultaneous integrated boost to gross disease. Patients then undergo pleurectomy/decortication within 14 days after completion of IMRT. Hypofractionated Radiation Therapy: Undergo accelerated hypofractionated IMRT Intensity-Modulated Radiation Therapy: Undergo accelerated hypofractionated IMRT Laboratory Biomarker Analysis: Correlative studies Therapeutic Conventional Surgery: Undergo pleurectomy/decortication
Measure Participants	0

6. Secondary Outcome

Title	Overall Survival (OS)
Description	No data displayed because Outcome Measure has zero total participants analyzed.
Time Frame	Up to 5 years post-treatment

Outcome Measure Data

Analysis Population Description

Data was not collected

Arm/Group Title	Treatment (Hypofractionated IMRT, Pleurectomy/Decortication)
Arm/Group Description	Patients undergo 5 fractions of accelerated hypofractionated IMRT over 1 week with simultaneous integrated boost to gross disease. Patients then undergo pleurectomy/decortication within 14 days after completion of IMRT. Hypofractionated Radiation Therapy: Undergo accelerated hypofractionated IMRT Intensity-Modulated Radiation Therapy: Undergo accelerated hypofractionated IMRT Laboratory Biomarker Analysis: Correlative studies Therapeutic Conventional Surgery: Undergo pleurectomy/decortication
Measure Participants	0

7. Secondary Outcome

Title	Pathologic Complete Response Rate (pCR)
Description	No data displayed because Outcome Measure has zero total participants analyzed.
Time Frame	Up to 5 years post-treatment

Outcome Measure Data

Analysis Population Description

Data was not collected

Arm/Group Title	Treatment (Hypofractionated IMRT, Pleurectomy/Decortication)
Arm/Group Description	Patients undergo 5 fractions of accelerated hypofractionated IMRT over 1 week with simultaneous integrated boost to gross disease. Patients then undergo pleurectomy/decortication within 14 days after completion of IMRT. Hypofractionated Radiation Therapy: Undergo accelerated hypofractionated IMRT Intensity-Modulated Radiation Therapy: Undergo accelerated hypofractionated IMRT Laboratory Biomarker Analysis: Correlative studies Therapeutic Conventional Surgery: Undergo pleurectomy/decortication
Measure Participants	0

Adverse Events

Time Frame	Adverse event data was collected from 10/2015 until 4/2018, 30 months.
Adverse Event Reporting Description	Dose limiting toxicity (DLT) defined as any treatment-related grade 3 or higher toxicity in the following categories: respiratory, upper GI, and cardiac. Also, any other grade 4 or 5 toxicity attributed to the therapy constitutes DLT. All AE's and SAE's, with grade and attribution were submitted to our DSMB as part of our quarterly summary reports. Serious adverse events were also reported individually to the DSMB and, where required, to our UCLA IRB within 2-10 days of awareness.
Arm/Group Title	Treatment (Hypofractionated IMRT, Pleurectomy/Decortication)
Arm/Group Description	Patients undergo 5 fractions of accelerated hypofractionated IMRT over 1 week with simultaneous integrated boost to gross disease. Patients then undergo pleurectomy/decortication within 14 days after completion of IMRT. Hypofractionated Radiation Therapy: Undergo accelerated hypofractionated IMRT Intensity-Modulated Radiation Therapy: Undergo accelerated hypofractionated IMRT Laboratory Biomarker Analysis: Correlative studies Therapeutic Conventional Surgery: Undergo pleurectomy/decortication
All Cause Mortality
	Treatment (Hypofractionated IMRT, Pleurectomy/Decortication)
	Affected / at Risk (%)	# Events
Total	2/2 (100%)
Serious Adverse Events
	Treatment (Hypofractionated IMRT, Pleurectomy/Decortication)
	Affected / at Risk (%)	# Events
Total	2/2 (100%)
Respiratory, thoracic and mediastinal disorders
Death	2/2 (100%)	2
Other (Not Including Serious) Adverse Events
	Treatment (Hypofractionated IMRT, Pleurectomy/Decortication)
	Affected / at Risk (%)	# Events
Total	2/2 (100%)
Gastrointestinal disorders
Nausea	1/2 (50%)	1
Vomiting	1/2 (50%)	1
General disorders
Weakness	1/2 (50%)	1

Limitations/Caveats

Due to the rarity of malignant pleural mesothelioma only two patients were enrolled and treated. There number as insufficient for any analysis.

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.