Maintenance Chemotherapy Versus Consolidative Stereotactic Body Radiation Therapy (SBRT) Plus Maintenance Chemotherapy for Stage IV Non-Small Cell Lung Cancer (NSCLC): A Randomized Phase II Trial

• ClinicalTrials.gov Identifier: NCT02045446
• Recruitment Status: Active, not recruiting
• First Posted: January 24, 2014
• Last Update Posted: August 13, 2020
• Sponsor: University of Texas Southwestern Medical Center
• Information provided by (Responsible Party): University of Texas Southwestern Medical Center

Study Description

Brief Summary:

The core hypothesis to be tested is that the use of consolidative SBRT followed by maintenance chemotherapy in patients with less than or equal to 6 metastatic sites (primary + 5) will improve progression free survival (PFS) compared to maintenance chemotherapy alone.

Condition or disease	Intervention/treatment	Phase
Stage IV Non-Small Cell Lung Cancer	Radiation: Stereotactic Body Radiation Therapy; Drug: Maintenance chemotherapy	Phase 2

Detailed Description:

This protocol is a randomized phase II trial of maintenance chemotherapy versus consolidative Stereotactic Body Radiation Therapy (SBRT) plus maintenance chemotherapy for patients with Stage IV non-small cell lung cancer (NSCLC).

Prior to accrual on the trial, patients with Stage IV NSCLC will be treated with standard first-line chemotherapy. Patients who achieve a partial response or stable disease by imaging criteria with fewer than or equal to six sites of oligometastatic disease will be randomized to maintenance chemotherapy or consolidative SBRT to all sites of disease (followed by maintenance chemotherapy at the medical oncologist's discretion). Choices of first line and maintenance chemotherapy will be determined by the medical oncologist based on clinical appropriateness.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 29 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Maintenance Chemotherapy Versus Consolidative Stereotactic Body Radiation Therapy (SBRT) Plus Maintenance Chemotherapy for Stage IV Non-Small Cell Lung Cancer (NSCLC): A Randomized Phase II Trial
• Actual Study Start Date: February 2014
• Estimated Primary Completion Date: January 2023
• Estimated Study Completion Date: January 2023

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Maintenance chemotherapy; FDA approved drugs for the study population: Bevacizumab, Docetaxel, Erlotinib, Gemcitabine, Pemetrexed	Drug: Maintenance chemotherapy; Maintenance chemotherapy
Experimental: Stereotactic Body Radiation Therapy; consolidative Stereotactic Body Radiation Therapy (SBRT) plus maintenance chemotherapy	Radiation: Stereotactic Body Radiation Therapy; Other Name: SBRT; Drug: Maintenance chemotherapy; Maintenance chemotherapy

Outcome Measures

Primary Outcome Measures :

1. Progression free survival [ Time Frame: 5 years ]
   Evaluate the effect of SBRT with or without maintenance chemotherapy versus maintenance chemotherapy alone on progression free survival

Secondary Outcome Measures :

1. Actuarial rate in-field local control [ Time Frame: 5 years ]
   To describe the actuarial rate in-field local control and rate of out-of-field disease progression
2. Toxicities [ Time Frame: 2 years ]
   To evaluate the safety of SBRT with metastatic NSCLC after prior chemotherapy
3. Overall survival [ Time Frame: 5 years ]
   To evaluate overall survival after SBRT followed by maintenance chemotherapy in comparison to maintenance chemotherapy alone.
4. Duration of maintenance chemotherapy [ Time Frame: 5 years ]
   To evaluate the duration of maintenance chemotherapy and time to initiation of third line systemic agent (chemotherapy or biologic agent)

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 99 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Patients must have biopsy proven metastatic NSCLC (Stage IV).
2. Patients must have received first line chemotherapy, from 4-6 cycles, and achieved stable disease or a partial response.
3. Patients receiving first-line erlotinib, gefitinib, or crizotinib for EGFR mutant-positive or EML4-ALK positive NSCLC will be excluded.
4. Age ≥ 18 years
5. Patients must have measurable disease at baseline.

6. Patients can have up to only 6 discrete active extracranial lesions (≤3 in the liver and ≤3 in the lung) identified by PET scan and also seen on correlative plain film, CT scan, or MRI within 8 weeks prior to the initiation of SBRT.

   1. For patients who have received prior radiotherapy to the primary site in the lung, residual PET activity is difficult to interpret and will not be considered a site of active disease if the CT appearance is stable or improved over an interval of at least three months
   2. Patients who previously received radiotherapy to the primary site will be ineligible if there is CT evidence of disease progression within the past 3 months.
   3. Patients with previously un-irradiated primary sites will be potentially eligible, but special considerations apply.
   4. Up to 2 contiguous vertebral metastases will be considered a single site of disease.
7. Patients must have a KPS >60
8. AST, ALT & Alkaline phosphates must be ≤ 2.5X the upper limit of normal. Total bilirubin must be within the limit of normal.
9. Patients should have adequate bone marrow function as defined by peripheral granulocyte count of ≥1500/mm³.
10. Patients should have adequate renal function (serum creatinine ≤1.5 times the ULN).
11. Females of childbearing potential should have a negative pregnancy test.
12. Patients who would be receiving SBRT for lung tumors who are known or suspected by the treating radiation oncologist to have compromised lung function must have a documented forced expiratory volume in 1 second (FEV1) ≥ 1L.
13. Patients must provide verbal and written informed consent to participate in the study.
14. Total bilirubin: within normal institutional limits

Exclusion Criteria:

1. Patients who previously received radiotherapy to the primary site with CT evidence of disease progression at the primary site within 3 months following the initial radiotherapy.
2. Patients with either untreated brain metastases or brain metastases treated within the past three months are ineligible
3. Patients with serious, uncontrolled, concurrent infection(s).
4. Significant weight loss (>10%) in the prior 3 months.
5. Because the tolerance dose of SBRT to the gastrointestinal tract is not established, patients with metastatic disease invading the esophagus, stomach, intestines, or mesenteric lymph nodes will not be eligible.
6. Patients with cutaneous metastasis of NSCLC.
7. Treatment for other carcinomas within the last five years, except cured non-melanoma skin and treated in-situ cancers.
8. Patients with more than 6 discrete extra-cranial lesions.
9. Participation in any investigational drug study within 4 weeks preceding the start of study treatment.
10. Unwillingness to participate or inability to comply with the protocol for the duration of the study.
11. Patients who are pregnant. Patients with reproductive capability will need to use adequate contraception during the time of participation in the study

Contacts and Locations

Locations

United States, Texas

UT Southwestern Medical Center

Dallas, Texas, United States, 75235

Sponsors and Collaborators

University of Texas Southwestern Medical Center

Investigators

• Principal Investigator: Puneeth Iyengar, MD; UTSW

  Study Documents (Full-Text)

Documents provided by University of Texas Southwestern Medical Center:

Study Protocol and Statistical Analysis Plan  [PDF] October 10, 2019

Informed Consent Form  [PDF] March 9, 2016

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Iyengar P, Wardak Z, Gerber DE, Tumati V, Ahn C, Hughes RS, Dowell JE, Cheedella N, Nedzi L, Westover KD, Pulipparacharuvil S, Choy H, Timmerman RD. Consolidative Radiotherapy for Limited Metastatic Non-Small-Cell Lung Cancer: A Phase 2 Randomized Clinical Trial. JAMA Oncol. 2018 Jan 11;4(1):e173501. doi: 10.1001/jamaoncol.2017.3501. Epub 2018 Jan 11.

• Responsible Party: University of Texas Southwestern Medical Center
• ClinicalTrials.gov Identifier: NCT02045446
• Other Study ID Numbers: STU 092013-070
• First Posted: January 24, 2014
• Last Update Posted: August 13, 2020
• Last Verified: July 2020

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms