HDCRT Plus Pembrolizumab in Advanced Malignancies

Solid Tumor Clinical Trial

— UVA-AM-001  

Official title:

A Pilot Study to Assess the Combination of High-Dose Conformal Radiation Therapy (HDCRT) and Pembrolizumab in Modulating Local and Systemic T-cell Responses in Advanced Malignancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02987166
• Other study ID #: 18488
• Status: Completed
• Phase: Phase 1
• Start date: March 21, 2017
• Est. completion date: February 10, 2020

Study information

• Verified date: December 2020
• Source: University of Virginia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is a pilot study to evaluate high-dose conformal radiation therapy (HDCRT) administered in combination with pembrolizumab in patients with solid tumors.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: February 10, 2020
• Est. primary completion date: January 13, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Subjects must have a histologically or cytologically proven advanced solid tumor malignancy for which palliative radiation is recommended. In solid tumors where pembrolizumab has been approved for use, patients may receive pembrolizumab as indicated, in the context of this protocol. In solid tumors where pembrolizumab has not been approved for use, the following criteria apply:

• Patients must be resistant to at least 1 prior conventional chemotherapy regimen or other standard of care regimen,

• Patient must have no remaining conventional treatment options proven to provide long-term disease control, and

• Patient has declined other conventional treatment options

• Palliative radiation therapy may be recommended for primary tumor and/or any metastatic site that is accessible to biopsy.

• At least one site of disease that is accessible to radiation and multiple biopsies. Subjects may have disease that is encompassed within the radiation field or may have known disease both inside and outside of the radiation field.

• Must be able to provide tissue from 2-3 separate biopsy procedures that will be completed throughout the course of the study.

• A performance status of 0, 1 or 2 on the ECOG Performance Scale.

• Subjects must demonstrate adequate organ function.

• A life expectancy = 6 months.

Exclusion Criteria:

• Requires urgent treatment with cytotoxic chemotherapy or other therapy is indicated.

• A diagnosis of immunodeficiency.

• A known history of active TB (Bacillus Tuberculosis).

• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with untreated brain metastases and patients who have had brain metastases re-treated with radiation will be excluded. Patients whom have either midline shift, or any signs of herniation (even if disease has been treated with GK) will be excluded. Subjects with previously treated brain metastases may participate provided they are 1) stable (without clinical evidence of progression) 2) are out at least 10 days from CNS radiation and 3) and are not using steroids as part of treatment for their brain lesions for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.

• Active autoimmune disease that has required systemic treatment in the past 2 years.

• A history of (non-infectious) pneumonitis that required steroids or current pneumonitis.

• An infection requiring systemic therapy.

• Pregnancy.

• HIV positivity.

• Evidence of active Hepatitis B virus or Hepatitis C virus.

• Significant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension, uncontrolled arrhythmias, or severe valvular heart disease, or a myocardial infarction within 6 months prior to the first dose of study treatment.

• Active bleeding disorders or evidence of chronic or acute disseminated intravascular coagulation (DIC).

• Class III or IV heart disease (New York Heart Association classification).

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor

Intervention

Radiation:
• High-Dose Conformal Radiation Therapy
24 Gy in 3 fractions of 8Gy each for bone and/or soft tissue lesions 30 Gy in 5 fractions of 6 Gy each for prostate gland

Drug:
• Pembrolizumab
200 mg

Locations

Country	Name	City	State
United States	University of Virginia	Charlottesville	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
James Larner, MD

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety: adverse event profile	Obtain preliminary data on the safety of HDCRT with immunotherapy, delivered concurrently (Arm A) or sequentially (Arms B and C)	30 days post-treatment for adverse events; 90 days post-treatment for serious adverse events
Primary	Immunologic: effect on T cell tumor infiltration	Estimate the effect of HDCRT, pembrolizumab, and the combination of HDCRT and pembrolizumab on CD8+ T cell and CD4+ T regulatory cell infiltration in tumors.	through day 43
Secondary	Immunologic: effect on lymphocyte composition of blood	Estimate the effect of HDCRT, pembrolizumab, and the combination of HDCRT and pembrolizumab on the lymphocyte composition of blood over time.	up to year 2