Randomized Study of Stereotactic Body Radiation Therapy (SBRT) in Patients With Oligoprogressive Metastatic Cancers of the Breast and Lung

NCT ID: NCT03808662

Last Updated: 2025-04-15

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 107 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-16
• Study Completion Date: 2026-01-31

Brief Summary

The purpose of this study is determine if receiving stereotactic body radiation(SBRT) when participants' metastatic tumors have just begun to grow increase the length of time before disease gets worse

Conditions

TNBC - Triple-Negative Breast Cancer; Triple Negative Breast Cancer; NSCLC; NSCLC Stage IV; Non Small Cell Lung Cancer; Non Small Cell Lung Cancer Metastatic; NSCLC Stage IV Without EGFR/ALK Mutation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1: Early Stereotactic Body Radiotherapy/SBRT

SBRT to all oligoprogressive sites

Group Type: EXPERIMENTAL

Sterotactic Body Radiotherapy/SBRT

Intervention Type: RADIATION

In general, it is recommended using 9-10 Gy x 3 or 10 Gy x 5 fractions given every other day. Physicians should try to give the highest BED whenever possible while respecting normal tissue tolerance. All lesions are recommended to receive a biologically effective dose (BED) of 60 Gy or higher (BED10≥70), assuming α/β ratio of 10 and using the linear-quadratic model: BED = nd x \[1 + d/(α/β)\] where n is number of fractions and d is dose per fraction. Sometimes BED ≥80 Gy is preferred, with lower doses ≥50 Gy allowed at the discretion of the treating physician for concerns about normal tissue toxicity.

Arm 2:Standard of Care

Group Type: ACTIVE_COMPARATOR

Standard of care

Intervention Type: DRUG

Standard of care per physician discretion

Interventions

Sterotactic Body Radiotherapy/SBRT

In general, it is recommended using 9-10 Gy x 3 or 10 Gy x 5 fractions given every other day. Physicians should try to give the highest BED whenever possible while respecting normal tissue tolerance. All lesions are recommended to receive a biologically effective dose (BED) of 60 Gy or higher (BED10≥70), assuming α/β ratio of 10 and using the linear-quadratic model: BED = nd x \[1 + d/(α/β)\] where n is number of fractions and d is dose per fraction. Sometimes BED ≥80 Gy is preferred, with lower doses ≥50 Gy allowed at the discretion of the treating physician for concerns about normal tissue toxicity.

Intervention Type: RADIATION

Standard of care

Standard of care per physician discretion

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age 18 or older
• Willing and able to provide informed consent
• Metastatic disease detected on imaging and histologically confirmed:

Triple negative breast cancer TNBC (ER <1%, PR <1%, her-2-neu 0- 1+ by IHC or FISH-negative or as determined by MD discretion)

OR NSCLC (without known EGFR mutation or ALK/ROS1 rearrangement)

OR Other high-risk breast cancer (per physician's discretion) progressed on hormone or systemic therapy, regardless of ER/HER2 status

OR NSCLC with EGFR, ALK, or ROS1 targetable molecular alterations with disease progression on first-line tyrosine kinase inhibitor

Note:

• Biopsy of metastasis prior to enrollment is per treating physician's discretion per standard of care. It is preferred but not required.
• These patients are selected for the study given the similar survival outcomes when given standard of care therapies
• Patient has received at least first-line prior treatment with systemic therapy (either cytotoxic or targeted, including maintenance therapies).
• Patients who received prior immunotherapy are allowed.
• Patients who had any prior radiation therapy near or overlapping with the oligoprogressive sites are allowed to enroll.
• Patients with the following medical conditions precluding them from participating in other systemic therapy or drug trials are allowed:
• active liver disease, including viral or other hepatitis, or cirrhosis
• any other significant medical condition not under control, including any acute coronary syndrome within the past 6 months.
• a permanent pacemaker
• a QTc > 480 ms in the baseline EKG
• peripheral neuropathy of grade >/= 2 per NCI CTCAE
• history or known autoimmune disease
• current chronic systemic steroid therapy or any immunosuppressive therapy
• history of primary immunodeficiency or solid organ transplant
• known positive human immunodeficiency virus (HIV), chronic or active hepatitis B or C, or active hepatitis A
• active infection requiring systemic antibiotic therapy
• Patients can have more than 5 metastases but can only have 1-5 oligo-progressive lesions.
• Oligoprogression, defined as Response Evaluation Criteria in Solid Tumors (RECIST) or Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) documented progression in up to 5 individual lesions

Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria as a guide:

1. At least a 20% increase in the sum of the longest diameter (LD) of the lesion, taking as reference the smallest sum LD recorded since the last imaging OR

2. The appearance of one or more new lesions OR

3. New/malignant FDG uptake in the absence of other indications of progressive disease or an anatomically stable lesion OR

4. >/= 5mm increase in the diameter sum of the lesion

OR

Using Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) as a guide:

1. >30% increase in 18F-FDG SUV peak, with >0.8 SUV units increase in tumor SUV from the baseline scan in pattern typical of tumor and not of infection/treatment effect OR

2. Visible increase in the extent of 18F-FDG tumor uptake OR

3. New 18F-FDG avid lesions typical of cancer (including new bone lesion) and not related to treatment effect and/or infection

OR

Development of a new soft tissue metastatic lesion at least 5mm in size or any new bone metastasis

OR

Progressive enlargement of a known metastasis on 2 consecutive imaging studies at least 2 months apart with a minimum 5mm increase in size

• All sites of oligoprogression can be safely treated
• Maximum 5 progressing metastases in any single extra-cranial organ system (i.e. lung, liver, bone)

a. If the clinical scenario deem that other forms of local therapy may be more suitable for the metastatic disease, such as surgical resection and interventional radiology-guided ablation, patients would be able to undergo other forms of local therapy with discussion with the PI

• No restriction on the total number of metastases
• Note: If the clinical scenario deem that other forms of local therapy may be more suitable for the metastatic disease, such as surgical resection and interventional radiology-guided ablation, patients would be able to undergo other forms of local therapy with discussion with the PI.
• For patients with brain metastases and oligoprogression elsewhere where stereotactic radiation to the brain is warranted, the brain lesions can be treated prior to randomization. This will not be counted toward the 5 progressive lesions.
• Any symptomatic metastatic sites requiring prompt palliative radiation (e.g. cord compression) can also be treated with standard of care radiation prior to randomization. This will not be counted toward the 5 progressive lesions.

1. If the clinical scenario deem that other forms of local therapy may be more suitable for the metastatic disease, such as surgical resection and interventional radiology-guided ablation, patients would be able to undergo other forms of local therapy with discussion with the PI.

Exclusion Criteria

• Pregnancy.
• Leptomeningeal disease.
• Serious medical comorbidities precluding radiotherapy, such as ataxia-telangiectasia or scleroderma.
• Any other condition which in the judgment of the investigator would make the patient inappropriate for entry into this study.

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

Sponsors

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nadeem Riaz, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, United States

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, United States

Memorial Sloan Kettering Bergen

Montvale, New Jersey, United States

Memorial Sloan Kettering Commack

Commack, New York, United States

Memorial Sloan Kettering Westchester

Harrison, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Memorial Sloan Kettering Rockville Centre

Rockville Centre, New York, United States

Memorial Sloan Kettering Nassau

Uniondale, New York, United States

Fred Hutchinson Cancer Research Center (Data Analysis Only)

Seattle, Washington, United States

Princess Margaret Hospital/Ontario Cancer Institute (Data Analysis Only)

Toronto, Ontario, Canada

Countries

United States; Canada

References

Tsai CJ, Yang JT, Shaverdian N, Patel J, Shepherd AF, Eng J, Guttmann D, Yeh R, Gelblum DY, Namakydoust A, Preeshagul I, Modi S, Seidman A, Traina T, Drullinsky P, Flynn J, Zhang Z, Rimner A, Gillespie EF, Gomez DR, Lee NY, Berger M, Robson ME, Reis-Filho JS, Riaz N, Rudin CM, Powell SN; CURB Study Group. Standard-of-care systemic therapy with or without stereotactic body radiotherapy in patients with oligoprogressive breast cancer or non-small-cell lung cancer (Consolidative Use of Radiotherapy to Block [CURB] oligoprogression): an open-label, randomised, controlled, phase 2 study. Lancet. 2024 Jan 13;403(10422):171-182. doi: 10.1016/S0140-6736(23)01857-3. Epub 2023 Dec 14.

Reference Type: DERIVED

PMID: 38104577 (View on PubMed)

Lee J, Koom WS, Byun HK, Yang G, Kim MS, Park EJ, Ahn JB, Beom SH, Kim HS, Shin SJ, Kim K, Chang JS. Metastasis-Directed Radiotherapy for Oligoprogressive or Oligopersistent Metastatic Colorectal Cancer. Clin Colorectal Cancer. 2022 Jun;21(2):e78-e86. doi: 10.1016/j.clcc.2021.10.009. Epub 2021 Nov 18.

Reference Type: DERIVED

PMID: 34903471 (View on PubMed)

Related Links

http://www.mskcc.org

Memorial Sloan Kettering Cancer Center

Other Identifiers

18-431

Identifier Type: -

Identifier Source: org_study_id