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

• ClinicalTrials.gov Identifier: NCT03808662
• Recruitment Status: Active, not recruiting
• First Posted: January 17, 2019
• Last Update Posted: February 2, 2024
• Sponsor: Memorial Sloan Kettering Cancer Center
• Information provided by (Responsible Party): Memorial Sloan Kettering Cancer Center

Study Description

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

Condition or disease	Intervention/treatment	Phase
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	Radiation: Sterotactic Body Radiotherapy/SBRT; Drug: Standard of care	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 107 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Precision Radiation for OligoMetastatIc and MetaStatic DiseasE (PROMISE)-004: Consolidative Use of Radiotherapy to Block (CURB) Oligoprogression
• Actual Study Start Date: January 16, 2019
• Estimated Primary Completion Date: January 2025
• Estimated Study Completion Date: January 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm 1: Early Stereotactic Body Radiotherapy/SBRT; SBRT to all oligoprogressive sites	Radiation: 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.
Active Comparator: Arm 2:Standard of Care	Drug: Standard of care; Standard of care per physician discretion

Outcome Measures

Primary Outcome Measures :

1. Progression Free Survival [ Time Frame: Up to 52 weeks after final participant is enrolled ]
   To study if the addition of early SBRT to extra-cranial oligo-progressive metastatic disease could prolong PFS compared to no SBRT. PFS is defined as the time from randomization to disease progression or death.

Secondary Outcome Measures :

1. Overall survival [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months ]

Eligibility Criteria

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

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.

Contacts and Locations

Locations

United States, New Jersey

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, United States, 07920

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, United States, 07748

Memorial Sloan Kettering Bergen

Montvale, New Jersey, United States, 07645

United States, New York

Memorial Sloan Kettering Commack

Commack, New York, United States, 11725

Memorial Sloan Kettering Westchester

Harrison, New York, United States, 10604

Memorial Sloan Kettering Cancer Center

New York, New York, United States, 10065

Memorial Sloan Kettering Rockville Centre

Rockville Centre, New York, United States, 11570

Memorial Sloan Kettering Nassau

Uniondale, New York, United States, 11553

United States, Washington

Fred Hutchinson Cancer Research Center (Data Analysis Only)

Seattle, Washington, United States, 98109

Canada, Ontario

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

Toronto, Ontario, Canada

Sponsors and Collaborators

Memorial Sloan Kettering Cancer Center

Investigators

• Principal Investigator: Nadeem Riaz, MD; Memorial Sloan Kettering Cancer Center

More Information

Additional Information:

Memorial Sloan Kettering Cancer Center 

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

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.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT03808662
• Other Study ID Numbers: 18-431
• First Posted: January 17, 2019
• Last Update Posted: February 2, 2024
• Last Verified: February 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: • Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made following one year after publication and for up to 36 months later. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Memorial Sloan Kettering Cancer Center:

SBRT; Stereotactic Body Radiotherapy; Non-hematology metatstatic cancer; non-CNS oligo-progressive disease; intracranial metastatic disease; Memorial Sloan Kettering Cancer Center; 18-431

Additional relevant MeSH terms:

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