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

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03808662

Collaborator

(none)

107

Enrollment

Locations

Arms

47.5

Anticipated Duration (Months)

11.9

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

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

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 :

Jan 16, 2019

Anticipated Primary Completion Date :

Jan 1, 2023

Anticipated Study Completion Date :

Jan 1, 2023

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

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

Progression Free Survival [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

Overall survival [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

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

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
The appearance of one or more new lesions OR
New/malignant FDG uptake in the absence of other indications of progressive disease or an anatomically stable lesion OR
/= 5mm increase in the diameter sum of the lesion

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

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
Visible increase in the extent of 18F-FDG tumor uptake OR
New 18F-FDG avid lesions typical of cancer (including new bone lesion) and not related to treatment effect and/or infection

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

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)

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.

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

	Site	City	State	Country	Postal Code
1	Memoral Sloan Kettering Basking Ridge	Basking Ridge	New Jersey	United States	07920
2	Memoral Sloan Kettering Monmouth	Middletown	New Jersey	United States	07748
3	Memorial Sloan Kettering Bergen	Montvale	New Jersey	United States	07645
4	Memorial Sloan Kettering Commack	Commack	New York	United States	11725
5	Memorial Sloan Kettering Westchester	Harrison	New York	United States	10604
6	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
7	New York Presbyterian Hospital-Weill Medical College of Cornell University (Data or Specimen Analysis)	New York	New York	United States	10065
8	Memorial Sloan Kettering Rockville Centre	Rockville Centre	New York	United States	11570
9	Memorial Sloan Kettering Nassau	Uniondale	New York	United States	11553