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

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.

Study Overview

• Status: Completed
• Conditions: Stage IV Non-Small Cell Lung Cancer
• Intervention / Treatment: Radiation: Stereotactic Body Radiation Therapy; Drug: Maintenance chemotherapy

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 Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75235
      • UT Southwestern Medical Center

Participation Criteria

Eligibility Criteria

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

Description

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, 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 diagnostic CT or PET/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 (section 4.3.2).
   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. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

    11.1 A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

    • Has not undergone a hysterectomy or bilateral oophorectomy; or
    • Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
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.

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 untreated brain metastases Patients with serious, uncontrolled, concurrent infection(s).
3. Significant weight loss (>10%) in the prior 3 months.
4. 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.
5. Patients with cutaneous metastasis of NSCLC.
6. Patients with more than 6 discrete extra-cranial lesions.
7. Participation in any investigational drug study within 4 weeks preceding the start of study treatment.
8. Unwillingness to participate or inability to comply with the protocol for the duration of the study.
9. Patients who are pregnant. Patients with reproductive capability will need to use adequate contraception during the time of participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: SBRT; Drug: Maintenance chemotherapy; Maintenance chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	Evaluate the effect of SBRT with maintenance chemotherapy versus maintenance chemotherapy alone on progression free survival. Time to the development of new lesions, progression of existing lesions, or death, whichever came first, represented the primary end point of progression-free survival. All evaluations of disease response used RECIST (v1.1) criteria, in which progressive disease is defined as "At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm."	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicities	To evaluate the safety of SBRT with metastatic NSCLC after prior chemotherapy	2 years
Overall Survival	To evaluate overall survival after SBRT followed by maintenance chemotherapy in comparison to maintenance chemotherapy alone.	5 years
Duration of Maintenance Chemotherapy	To evaluate the duration of maintenance chemotherapy and time to initiation of third line systemic agent (chemotherapy or biologic agent)	5 years
In-field Local Control Versus Out-of-field Disease Progression	Number of occurances of in-field local control and rate of out-of-field disease progression	5 years

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Investigators: Principal Investigator: Puneeth Iyengar, MD, UTSW

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2014
• Primary Completion (Actual): February 17, 2022
• Study Completion (Actual): May 2, 2022

Study Registration Dates

• First Submitted: January 14, 2014
• First Submitted That Met QC Criteria: January 22, 2014
• First Posted (Estimate): January 24, 2014

Study Record Updates

• Last Update Posted (Actual): May 23, 2023
• Last Update Submitted That Met QC Criteria: April 25, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: STU 092013-070