Single-arm Phase 2 Study to Examine Pembrolizumab and Concurrent Radiation to Induce an Abscopal Effect in Patients With Previously Treated Carcinoma of Unknown Primary (CUP16-268)
Overview
- Phase
- Phase 2
- Intervention
- Pembrolizumab
- Conditions
- Carcinoma, Unspecified Site
- Sponsor
- Hoosier Cancer Research Network
- Enrollment
- 14
- Locations
- 2
- Primary Endpoint
- Abscopal Response Rate
- Status
- Terminated
- Last Updated
- 2 years ago
Overview
Brief Summary
Single-arm phase 2 study to examine pembrolizumab and concurrent radiation to induce an abscopal effect in patients with previously treated carcinoma of unknown primary (CUP16-268)
Detailed Description
This is a proof-of-principle single-arm phase 2 study in patients with previously treated CUP. All patients receive pembrolizumab combined with Radiation Therapy (RT) to a metastatic site, so as to induce an abscopal tumor response. The treatment combination will be repeated with RT delivery to a second metastatic site in a non-overlapping RT field. The results will be compared with historical control. The primary endpoint is the confirmed response rate (RR) in a non-irradiated site based on best responding abscopal lesion. This study will also evaluate the following secondary endpoints: RR in a non-irradiated site based on RECIST 1.1, adverse events, progression-free survival (PFS), overall survival (OS), time-to-progression (TTP), and disease control rate (DCR).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
- •Age ≥ 18 years at the time of consent.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2 within 28 days prior to registration.
- •Archival tissue must be available and identified during screening and shipped prior to Day -
- •If archival tissue is not available and the subject is not undergoing a standard of care biopsy, the subject must undergo a research biopsy to obtain fresh tissue prior to start of treatment.
- •Carcinoma of unknown primary after the following diagnostic procedures have been performed if clinically indicated and are unrevealing of the primary site:
- •Complete history and clinically appropriate physical
- •CT scan of chest, abdomen, and pelvis
- •Directed evaluation of symptomatic areas
- •Mammogram in women
Exclusion Criteria
- •Prior radiation to an area of the body which, if included in the current radiation field, poses an unacceptably high risk of toxicity in the opinion of the investigator. NOTE: A prior field that overlaps with the current field, by itself, does not exclude the patient.
- •Any of the following
- •-Melanoma. NOTE: Positive tumor staining for S-100 or HMB45 alone does not exclude patients.
- •--If immunostains are performed, and any of the below tests are positive:
- •Hematologic CD45+ (others such as CD2, CD20, CD30, CD43 also suggest hematologic origin)
- •Lung or thyroid origin (Thyroid Transcription Factor \[TTF-1\]). NOTE: Patients with biopsy proven TTF-1 positive tumor who do not have clinical evidence for either lung or thyroid cancer (e.g. a dominant lung mass) are still eligible.
- •Progressed on 4 or more lines of prior chemotherapy for this cancer. NOTE: Bisphosphonates and neoadjuvant/adjuvant anticancer therapies (including locally directed therapies) do not count as a line of therapy with regard to this exclusion criteria.
- •Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
- •Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
- •Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
Arms & Interventions
Single Arm Assignment
Pembrolizumab + External Beam Radiation Therapy
Intervention: Pembrolizumab
Single Arm Assignment
Pembrolizumab + External Beam Radiation Therapy
Intervention: External Beam Radiation Therapy
Outcomes
Primary Outcomes
Abscopal Response Rate
Time Frame: From Cycle 3, Day 1 (each cycle is 21 days) (C3D1) until death or up to a maximum of 19 months
Evaluate the abscopal response rate in Carcinoma of Unknown Primary (CUP) patients treated with the combination of pembrolizumab plus radiotherapy. Best abscopal response is defined as the frequency of patients whose best responding abscopal lesion demonstrates at least a 30% decrease in its longest diameter from baseline (Golden et al., 2015).
Secondary Outcomes
- Response Rate(From Cycle 1, Day 1 (each cycle is 21 days) until death or up to a maximum of 19 months)
- Evaluate Treatment-related Toxicity.(From Cycle 1, Day 1 (each cycle is 21 days) until death or up to a maximum of 9 months)
- Progression-Free Survival(From Cycle 1, Day 1 (each cycle is 21 days) until progression or death or up to a maximum of 6 months)
- Overall Survival(From Cycle 1, Day 1 (each cycle is 21 days) until death or up to a maximum of 19 months)
- Time-to-Progression(From Cycle 1, Day 1 (each cycle is 21 days) until death or up to a maximum of 6 months)
- Disease Control Rate(From Cycle 1, Day 1 (each cycle is 21 days) to a maximum of 19 months)
- Explore the Association Between Response Rate (RR) and Other Endpoints (e.g., OS, PFS)(From Cycle 1, Day 1 (each cycle is 21 days) until death or up to a maximum of 19 months)