Study of Pembrolizumab and Concurrent Radiation in Patients With Previously Treated Carcinoma of Unknown Primary

NCT03396471 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: HCRN CUP16-268
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 2

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)

Conditions

Carcinoma, Unspecified Site

Outcome Measures

Primary Outcomes (1)

• Abscopal Response Rate

  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).

  From Cycle 3, Day 1 (each cycle is 21 days) (C3D1) until death or up to a maximum of 19 months

Secondary Outcomes (7)

• 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

Study Arms (1)

Single Arm Assignment

EXPERIMENTAL

Pembrolizumab + External Beam Radiation Therapy

Drug: Pembrolizumab; Radiation: External Beam Radiation Therapy

Interventions

Pembrolizumab DRUG

200mg IV at day -21, then day 1 of each 21-day cycle for a maximum of 24 continuous months of Pembrolizumab (35 cycles) from Cycle 1 Day 1 (C1D1) can be administered.

Also known as: Keytruda

Single Arm Assignment

External Beam Radiation Therapy RADIATION

20-30 Gy over five fractions for up to two cycles.

Also known as: External Beam Radiation Therapy (EBRT)

Single Arm Assignment

Eligibility Criteria

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

You may qualify if:

• 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 -21. 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
• Colonoscopy in patients with liver metastasis or an elevated CEA
• Direct pathologic comparison with prior tumor specimens, where possible, even if prior tumor is early-stage or clinically remote from current disease NOTE: Immunohistochemical stains will be performed according to institutional standards. If a primary carcinoma is identified, the patient should undergo treatment as appropriate for that primary tumor and not be enrolled in the study. The above diagnostic workup does not need to be performed if: (1) it was previously completed at the time of original diagnosis or (2) the investigator does not believe the workup has clinical utility at the current time, given that the patient has received interval therapy.
• Histologic confirmation of metastatic adenocarcinoma, poorly differentiated non-small cell carcinoma, or poorly differentiated squamous carcinoma. NOTE: Pathology consultation at Mayo Clinic is recommended if clinically indicated. One scenario is where unknown primary is the most likely diagnosis but immunostains show relatively site-specific marker staining (e.g., CD45, TTF1, chromogranin, GATA3, PAX8, PSA, melanocytic markers). Information provided for pathology consultation should include recent H\&P and imaging reports.
• If and when available, submission of genomic sequencing and expression profiling results is mandatory. Results of testing are not required prior to treatment.
• At least one measurable lesion (per RECIST 1.1) outside the planned RT fields.
• Stable or progressive disease after, or was unable to tolerate, at least one line of prior anticancer therapy for this disease. NOTE: For patients with stable disease, it is strongly encouraged to confirm the presence of active disease (eg, demonstrating 18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose (FDG) avidity via PET or repeat biopsy).

You may not qualify if:

• 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.
• 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.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
• Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. NOTE: Inhaled steroids or steroid injections for joint disease are allowed.
• Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected).
• Prior severe allergic reactions to a monoclonal antibody or hypersensitivity to pembrolizumab or any of its excipients.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.

Sponsors & Collaborators

• Hoosier Cancer Research Network: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Carcinoma

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Results Point of Contact

• Title: Annesha Majumdar
• Organization: Hoosier Cancer Research Network

amajumdar@hoosiercancer.org

3179212050

Study Officials

• Harry Yoon

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 27, 2017
• First Posted: January 11, 2018
• Study Start: February 1, 2018
• Primary Completion: August 12, 2021
• Study Completion: March 2, 2023
• Last Updated: April 18, 2024
• Results First Posted: December 23, 2022

Record last verified: 2024-04

Locations

US (2)