A Window of Opportunity Study to Investigate Mechanisms of Actions of Novel Therapeutic Agents in Patients With Resectable Solid Tumor Malignancies

A Phase 1b Window of Opportunity Study to Investigate Mechanisms of Actions of Novel Therapeutic Agents in Patients With Resectable Solid Tumor Malignancies

This is a single-institution, single arm, open label, window of opportunity clinical trial that will act as a Master Protocol with a primary objective to assess pharmacodynamic effects of the novel study drugs in subjects with resectable solid tumor malignancies.

Each Sub-protocol conducted under the Master Protocol will evaluate different novel therapeutic agent(s).

Estimated enrollment is 15 subjects per Sub-Protocol.

Study Overview

• Status: Terminated
• Conditions: Solid Tumor
• Intervention / Treatment: Drug: Epacadostat

Detailed Description

Patients will have a short-course (4-weeks) administration of a given compound in the timeframe between the diagnostic biopsy and the surgical resection. A pre-treatment tumor biopsy will be obtained, and blood samples will be collected before, during, and at the end of treatment.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Must have biopsy-proven solid tumor that is eligible for elective surgical resection, disease does not require immediate therapy, and there is NO approved/ standard therapy available that is shown to prolong overall survival.
2. ECOG performance status of 0 or 1.
3. Must have a tumor lesion that is amenable to biopsy, and willing to undergo biopsy.
4. Willing to provide tissue and blood samples for research.

Exclusion Criteria:

1. The following solid tumors are NOT eligible: Primary brain tumor, Ocular melanoma, Head and neck cancer, Breast cancer, Prostate cancer, Testicular cancer, and Stage III rectal cancer.
2. Any active malignancy within 3 years prior, except: Adequately treated basal cell or squamous cell skin cancer, or early stage cancers (carcinoma in situ or stage 1) treated with curative intent.
3. Any uncontrolled intercurrent illness, including but not limited to: Symptomatic congestive heart failure, Unstable angina pectoris or coronary angioplasty or stenting within 6 months prior to enrollment, Cardiac arrhythmia, Psychiatric illness or social situations that would limit compliance with study requirements, or Ongoing or active infection.
4. Any known sensitivity to or history of allergic reaction to compounds of similar chemical or biological composition of study drug(s).
5. Unwilling or unable to follow the study schedule.

Other protocol defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Sub-Protocol A; Epacadostat	Drug: Epacadostat; Drug is taken orally two times per day for 14 days, prior to surgical resection of tumor.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacodynamic effects as measured by changes in biomarkers in pre- and post-dose tumor and blood specimens	To establish baseline levels and measure pharmacodynamic biomarker changes in tumor and/or blood samples after treatment with the study drug. Sub- Protocol A will focus on changes in CD8+ T cells, CD4+Foxp3+ cells, NK cells, DCs and immune checkpoints.	Approximately 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability as measured by incidence of AEs (Adverse Events)	To assess the safety and tolerability of the study drug in the pre-surgical setting graded according to Common Terminology Criteria for Adverse Events (CTCAE), version 4.0.	Approximately 1 year
Pathological Response Rate as measured by correlation of biomarkers in tumor and/or blood specimens	To evaluate pathological response rate of solid tumor malignancies in subjects receiving neo-adjuvant treatment with the study drug and to assess a possible correlation with biomarkers either in the tumor specimens either in the bloods samples and the pathological response.	Approximately 1 year
Overall Survival	To determine the overall survival (OS) status of subject treated which the study drug at 6 months, 1 year and 2 year	Approximately 2 years

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: Incyte Corporation

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 6, 2019
• Primary Completion (ACTUAL): July 30, 2021
• Study Completion (ACTUAL): July 30, 2021

Study Registration Dates

• First Submitted: March 2, 2018
• First Submitted That Met QC Criteria: March 19, 2018
• First Posted (ACTUAL): March 20, 2018

Study Record Updates

• Last Update Posted (ACTUAL): August 26, 2021
• Last Update Submitted That Met QC Criteria: August 20, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: J17168; IRB00156271 (OTHER: JHM IRB); I-24360-17-13 (OTHER: Incyte Corporation)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No