Stereotactic Body Radiation Therapy (SBRT) in Newly Diagnosed Advanced Staged Lung Adenocarcinoma (Sindas)

NCT ID: NCT02893332

Last Updated: 2021-02-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-15
• Study Completion Date: 2020-08-30

Brief Summary

To tested if the adding of consolidative SBRT to TKI in EGFR mutated patients with less than or equal to 5 metastatic sites (primary + 5) will improve progression free survival (PFS) compared to TKI alone.

Detailed Description

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

Prior to accrual on the trial, patients with Stage IV NSCLC will be tested with positive EGFR mutation. Patients who with fewer than or equal to 5 sites of oligometastatic disease will be randomized toTKI or consolidative SBRT to all sites of disease (followed by TKI at the medical oncologist's discretion). Choices of TKI will be determined by the medical oncologist based on clinical appropriateness.

Conditions

Stage IV EGFR Mutated Non-Small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

TKI without SBRT

Newly diagnosed Patients will be placed on EGFR-TKI, ,Gefitinib 250mg po qd or Tarceva 150mg po qd for their metastatic EGFR-mutant stage IV oligometastatic disease.

The oligometastatic disease will not receive SBRT

Group Type: ACTIVE_COMPARATOR

TKI (Gefitinib or Tarceva )

Intervention Type: DRUG

A first line TKI (Gefitinib 250mg po qd or Tarceva 150mg po qd ) will be administered according to the standard dosing of the drug for metastatic NSCL, no local therapy apply to oligo-metastatic sites.

TKI with SBRT

experimental: Oligometastatic Non-Small Cell Lung Cancer Newly diagnosed patients will be placed on EGFR-TKI, Gefitinib 250mg po qd or Tarceva 150mg po qd, for their metastatic EGFR-mutant stage IV oligometastatic disease. All patients will TKI, Gefitinib 250mg po qd or Tarceva 150mg po qd, and SBRT at the same time.

SBRT to up to 5 sites. The SBRT dose range from 5 Gy per fraction to 8 Gy per fraction. SBRT deliver within 5 fractions.

Group Type: EXPERIMENTAL

Radiation: SBRT

Intervention Type: RADIATION

A first line TKI (Gefitinib 250mg po qd or Tarceva 150mg po qd ) will be administered according to the standard dosing of the drug for metastatic NSCL during a 1-week run-in period after which SBRT will be delivered to the all oligometastatic lesions concurrently with the TKI. The SBRT dose will be , ranging from at 25Gy (5 Gy per fraction) to 40 Gy (8 Gy per fraction).

TKI (Gefitinib or Tarceva )

Intervention Type: DRUG

A first line TKI (Gefitinib 250mg po qd or Tarceva 150mg po qd ) will be administered according to the standard dosing of the drug for metastatic NSCL, no local therapy apply to oligo-metastatic sites.

Interventions

Radiation: SBRT

A first line TKI (Gefitinib 250mg po qd or Tarceva 150mg po qd ) will be administered according to the standard dosing of the drug for metastatic NSCL during a 1-week run-in period after which SBRT will be delivered to the all oligometastatic lesions concurrently with the TKI. The SBRT dose will be , ranging from at 25Gy (5 Gy per fraction) to 40 Gy (8 Gy per fraction).

Intervention Type: RADIATION

TKI (Gefitinib or Tarceva )

A first line TKI (Gefitinib 250mg po qd or Tarceva 150mg po qd ) will be administered according to the standard dosing of the drug for metastatic NSCL, no local therapy apply to oligo-metastatic sites.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Newly diagnosed metastatic lung adenocarcinoma (recurrent or de novo) harboring sensitizing EGFR mutations (L858R, exon 19 deletion, G719A, L861Q, S768I, exon 19 insertions) with oligometastatic disease (≤5 discrete lesions of disease irrespective of location, inclusive of the primary lesion):

• all sites of disease must be amenable to definitive treatment with a local therapy (surgical resection, stereotactic radiosurgery, ablation and conventional radiation therapy) as determined by surgery, interventional radiology and radiation oncology
• all intrathoracic lymph nodes (including hilar, mediastinal, and supraclavicular nodal disease) are considered 1 discrete lesion.
• No brain metastasis is allowed.
• Patients already started on erlotinib are eligible as long as their sites of disease are determined to be eligible for definitive local therapy by consensus of the principal investigators within 12 weeks of the patient first taking erlotinib.
• Lung adenocarcinoma histology confirmed
• Karnofsky Performance Status ≥ 70%
• Adequate bone marrow, liver and renal function, as specified below:

• Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L
• Hemoglobin ≥ 8 g/dL
• Platelets ≥ 100 x 109/L
• Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN) (except for patients with documented Gilbert's Syndrome)
• AST and ALT ≤ 2.5 x ULN or ≤ 5 x ULN if liver metastases are present
• Serum creatinine ≤ 1.5 x upper limit of normal or creatinine clearance ≥ 60ml/min for patients with creatinine levels above institutional normal.
• For women of child-bearing potential, negative pregnancy test within 14 days prior to starting treatment
• Men and women of childbearing age must be willing to use effective contraception while on treatment and for at least 3 months thereafter

Exclusion Criteria

• Treatment with TKI prior to developing metastatic disease
• Malignant pleural effusion or pleural disease
• Leptomeningeal disease or brain metastasis.
• Any site of disease that is not amenable to definitively local therapy including surgery or radiation therapy
• Women who are breastfeeding or pregnant
• Concurrent malignancies other than non-melanoma skin cancer that require active ongoing treatment.
• Any medical co-morbidities that would preclude surgery or radiation therapy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sichuan Provincial People's Hospital

OTHER

Sponsor Role: lead

Responsible Party

ming zeng, MD

Director of Cancer Center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ming Zeng, MD PhD

Role: STUDY_CHAIR

Sichuan Provincial People Hospital

Locations

Sichuan PPH, Cancer Center

Chengdu, Sichuan, China

Countries

China

References

Wang XS, Bai YF, Verma V, Yu RL, Tian W, Ao R, Deng Y, Zhu XQ, Liu H, Pan HX, Yang L, Bai HS, Luo X, Guo Y, Zhou MX, Sun YM, Zhang ZC, Li SM, Cheng X, Tan BX, Han LF, Liu YY, Zhang K, Zeng FX, Jia L, Hao XB, Wang YY, Feng G, Xie K, Lu Y, Zeng M. Randomized Trial of First-Line Tyrosine Kinase Inhibitor With or Without Radiotherapy for Synchronous Oligometastatic EGFR-Mutated Non-Small Cell Lung Cancer. J Natl Cancer Inst. 2023 Jun 8;115(6):742-748. doi: 10.1093/jnci/djac015.

Reference Type: DERIVED

PMID: 35094066 (View on PubMed)

Other Identifiers

2016 15-1

Identifier Type: -

Identifier Source: org_study_id