SBRT + PD-1/PDL-1 Inhibiting Therapy for Advanced Solid Tumors After Dz Control on PD-1/PDL-1 Tx

NCT03220854 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: MCC-16-12436P30CA016059
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to find out if having radiation therapy and continuing immunotherapy can improve the benefit of immunotherapy. There have been reports of patients who were treated with radiation therapy that not only caused the treated tumors to shrink or stop growing, but also resulted in tumors that had not been treated in other parts of the body to shrink or stop growing. This effect is thought to be brought about by cells in the body's immune system that become active as a result of the effects of radiation therapy. If radiation therapy can stimulate the immune system, it may be possible for immunotherapy to be helpful again in treating a cancer that the immunotherapy drug helped treat before. This study will also check if receiving immunotherapy at the end of radiation therapy has any effect on the side effects of radiation therapy or immunotherapy.

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Improved Disease Control

  1. Number of patients with improved disease control at 24 weeks following RT \[Time Frame: up to 24 weeks following RT\] 1a. Number of participants with improved disease control (SD, PR or CR) at 24 weeks per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) 1b. For participants enrolled with brain metastases: number of participants with improved disease (SD, PR or CR) control at 24 weeks per per Response Assessment in Neuro-Oncology for Brain Metastases (RANO-BM)

  Up to 24 weeks following SRT

Secondary Outcomes (7)

• Number of Patients Alive and Free From Progression at 24 Weeks Following SRT Per Unidimensional Immune-related Response Criteria (irRC)

  Up to 24 weeks following SRT

• Number of Participants With Treatment Response in Irradiated Tumor Sites

  Up to 24 weeks following SRT

• Number of Participants With Treatment Response in Non-irradiated Tumor Sites

  Up to 24 weeks post-RT

• Number of Patients Alive

  2 years following SRT

• Number of Participants With Grade 3 or Greater Toxicity

  Through 8 weeks following SRT

Study Arms (3)

A: SBRT (body) irradiation only

EXPERIMENTAL

Patients will receive a standard treatment regimen of SRT (refer to Section 6.3). The term SRT encompasses all radiotherapy using a stereotactic setup, both stereotactic radiosurgery (SRS) for metastatic lesions in the brain and stereotactic body radiotherapy (SBRT) for SRT delivered to all other locations

Radiation: Stereotactic radiotherapy; Other: Biological: humanized anti-PD-1 monoclonal antibody; Other: Biological: humanized anti-PD-L1 monoclonal antibody

B: Patients receiving SBRT and SRS (body and brain) irradiation

EXPERIMENTAL

Patients will receive a standard treatment regimen of SRT (refer to Section 6.3). The term SRT encompasses all radiotherapy using a stereotactic setup, both stereotactic radiosurgery (SRS) for metastatic lesions in the brain and stereotactic body radiotherapy (SBRT) for SRT delivered to all other locations

Radiation: Stereotactic radiotherapy; Other: Biological: humanized anti-PD-1 monoclonal antibody; Other: Biological: humanized anti-PD-L1 monoclonal antibody

C: Patients receiving SRS (brain) irradiation only

EXPERIMENTAL

Patients will receive a standard treatment regimen of SRT (refer to Section 6.3). The term SRT encompasses all radiotherapy using a stereotactic setup, both stereotactic radiosurgery (SRS) for metastatic lesions in the brain and stereotactic body radiotherapy (SBRT) for SRT delivered to all other locations

Radiation: Stereotactic radiotherapy; Other: Biological: humanized anti-PD-1 monoclonal antibody; Other: Biological: humanized anti-PD-L1 monoclonal antibody

Interventions

Stereotactic radiotherapy RADIATION

Treatment will be planned to deliver a total of 18 to 60 Gy to the planning target volume (PTV) in 3 to 5 fractions over 1 to 2 weeks.

Also known as: SRT

A: SBRT (body) irradiation only; B: Patients receiving SBRT and SRS (body and brain) irradiation; C: Patients receiving SRS (brain) irradiation only

Biological: humanized anti-PD-1 monoclonal antibody OTHER

Standard of Care - patient will continue to be given the same PD-1 inhibitor they were receiving prior to study registration

Also known as: PD-1

A: SBRT (body) irradiation only; B: Patients receiving SBRT and SRS (body and brain) irradiation; C: Patients receiving SRS (brain) irradiation only

Biological: humanized anti-PD-L1 monoclonal antibody OTHER

Standard of Care - patient will continue to be given the same PD-L1 inhibitor they were receiving prior to study registration

Also known as: PD-L1

A: SBRT (body) irradiation only; B: Patients receiving SBRT and SRS (body and brain) irradiation; C: Patients receiving SRS (brain) irradiation only

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathologically-proven diagnosis of a solid tumor malignancy
• One of the following criteria must be met:
• Clinical or radiographic evidence of disease control (defined as best response of stable disease (SD) or partial response (PR) or combination of both for ≥ 16 weeks) without evidence of complete response (CR) or progression OR
• Clinical or radiographic evidence of disease progression during treatment with PD-1 or PD-L1 inhibiting therapy, following previous tumor response (CR, PR, or SD for ≥ 16 weeks) to PD-1 or PD-L1 inhibiting therapy, and, for patients who discontinued PD-1 or PD-L1 inhibiting therapy during response to therapy, disease progression must have occurred following at least 8 weeks of re-treatment with PD-1 or PD-L1 inhibiting therapy Note: Both the treating medical oncologist and radiation oncologist must be in agreement with determination of disease progression.
• Administration of a PD-1 or PD-L1 inhibitor within 60 days prior to study registration
• Determination by the treating radiation oncologist that the patient is a candidate for SRT (ie, radiation therapy with a stereotactic setup) Note: All brain metastases will receive stereotactic radiotherapy (SRT).
• The total number of tumors requiring SRT must be ≤ 5 Note: Regardless of the number of brain metastases that will be treated with SRT, the brain metastases will be considered to be one tumor.
• Measurable disease by RECIST v1.1 that will not undergo SRT and that is amenable to monitoring Note: all brain metastases will receive SRT. Therefore, a patient with brain metastases that will be treated with SRT must also have extracranial disease that will not undergo SRT and that is amenable to monitoring
• Determination by the treating medical oncologist that the patient is a candidate to continue the PD-1 or PD-L1 inhibiting therapy that had previously provided disease control
• Age ≥ 18 years
• Karnofsky Performance Status score of ≥ 60 %
• A woman of childbearing potential (WCBP), defined as a woman who is \< 60 years of age and has not had a hysterectomy, must have a documented negative serum pregnancy test within 14 days prior to initiating study treatment
• Ability to understand and willingness to sign the consent form

You may not qualify if:

• Other anti-cancer therapy administered between the time of tumor response to PD-1 or PD-L1 therapy and time of study enrollment Note: Patients treated with a combination of PD-1 or PD-L1 inhibiting therapy and other immunotherapy are eligible; patients taking hormonal anti-cancer therapies or steroids for central nervous system (CNS) edema management that, in the opinion of the investigator, are appropriate to continue are eligible.
• Administration of any investigational agent within 4 weeks prior to initiating study treatment
• Known active hepatitis B or C
• Pregnancy or breastfeeding
• Medical, psychological, or social condition that, in the opinion of the investigator, may increase the patient's risk or limit the patient's adherence with study requirements

Sponsors & Collaborators

• Virginia Commonwealth University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, 23298, United States

Location

MeSH Terms

Interventions

Radiosurgery

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Limitations and Caveats

Incomplete objectives due to early closure to accrual of trial.

Results Point of Contact

• Title: Alfredo I Urdaneta
• Organization: Virginia Commonwealth University Massey Cancer Center

MasseyRadOnc@vcu.edu

(804) 828-0450

Study Officials

• Alfredo Urdaneta, M.D.

  Massey Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Steriotactic Radiotherapy followed by a commercially available PD-1 or PD-L1 inhibitor drug

Study Record Dates

• First Submitted: July 14, 2017
• First Posted: July 18, 2017
• Study Start: October 10, 2017
• Primary Completion: January 27, 2020
• Study Completion: September 22, 2021
• Last Updated: January 10, 2022
• Results First Posted: January 15, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)