HDCRT Plus Pembrolizumab in Advanced Malignancies

NCT02987166 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 18488
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Solid Tumor

Keywords

immunotherapy; pembrolizumab; MK-3475; High-dose conformal radiation therapy; HDCRT; advanced solid tumor

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (1)

• Immunologic: effect on lymphocyte composition of blood

  up to year 2

Study Arms (3)

Arm A: HDCRT administered with first dose of pembrolizumab

EXPERIMENTAL

Pembrolizumab (200 mg) plus HDCRT (24 Gy in 3 fractions of 8 Gy each for bone and/or soft tissue lesions; 30 Gy in 5 fractions of 6 Gy each for the prostate gland) are both administered beginning on day 1. Pembrolizumab (200 mg) will be administered on days 1, 43, 64, 85. Subjects who have measurable disease outside of the radiation field and who have derived benefit from the 4 doses of pembrolizumab may continue to receive pembrolizumab every 3 weeks for up to 2 years. HDCRT will be administered to the primary tumor and/or sites of metastatic disease (1 or more sites permitted) over a period of 3-5 days. The length of time for administration of the HDCRT will depend on the site of disease that is to be radiated. HDCRT will begin on day 1.

Radiation: High-Dose Conformal Radiation Therapy; Drug: Pembrolizumab

Arm B: HDCRT administered between doses 1& 2 of pembrolizumab

EXPERIMENTAL

Pembrolizumab (200 mg) begins on day 1. HDCRT (24 Gy in 3 fractions of 8 Gy each for bone and/or soft tissue lesions; 30 Gy in 5 fractions of 6 Gy each for the prostate gland) begins on day 22. Pembrolizumab (200 mg) will be administered on days 1, 43, 64, 85. Subjects who have measurable disease outside of the radiation field and who have derived benefit from the 4 doses of pembrolizumab may continue to receive pembrolizumab every 3 weeks for up to 2 years. HDCRT will be administered to the primary tumor and/or sites of metastatic disease (1 or more sites permitted) over a period of 3-5 days. The length of time for administration of the HDCRT will depend on the site of disease that is to be radiated. HDCRT will begin on day 22.

Radiation: High-Dose Conformal Radiation Therapy; Drug: Pembrolizumab

Arm C: HDCRT administered prior to first dose of pembrolizumab

EXPERIMENTAL

Pembrolizumab (200 mg) begins on day 1. HDCRT (24 Gy in 3 fractions of 8 Gy each for bone and/or soft tissue lesions; 30 Gy in 5 fractions of 6 Gy each for the prostate gland) begins on day 1. Pembrolizumab will be administered on days 22, 43, 64, and 85. Subjects who have measurable disease outside of the radiation field and who have derived benefit from the four doses of pembrolizumab may continue to receive pembrolizumab every 3 weeks for up to 2 years. HDCRT will be administered to the primary tumor and/or sites of metastatic disease (1 or more sites permitted) over a period of 3-5 days. The length of time for administration of the HDCRT will depend on the site of disease that is to be radiated. HDCRT will begin on day 1.

Radiation: High-Dose Conformal Radiation Therapy; Drug: Pembrolizumab

Interventions

High-Dose Conformal Radiation Therapy RADIATION

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

Also known as: HDCRT

Arm A: HDCRT administered with first dose of pembrolizumab; Arm B: HDCRT administered between doses 1& 2 of pembrolizumab; Arm C: HDCRT administered prior to first dose of pembrolizumab

Pembrolizumab DRUG

200 mg

Also known as: Keytruda, MK-3475

Arm A: HDCRT administered with first dose of pembrolizumab; Arm B: HDCRT administered between doses 1& 2 of pembrolizumab; Arm C: HDCRT administered prior to first dose of pembrolizumab

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• James Larner, MD: lead

Study Sites (1)

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Interventions

pembrolizumab

Study Officials

• James Larner, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: James Larner, MD

Study Record Dates

• First Submitted: November 30, 2016
• First Posted: December 8, 2016
• Study Start: March 21, 2017
• Primary Completion: January 13, 2020
• Study Completion: February 10, 2020
• Last Updated: December 16, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)