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Testing Whether the Combination of Two Immunotherapy Drugs Have Activity in Recurrent or Persistent Clear Cell Ovarian Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03602586
Recruitment Status : Active, not recruiting
First Posted : July 27, 2018
Results First Posted : December 23, 2022
Last Update Posted : January 26, 2023
Sponsor:
Collaborator:
NRG Oncology
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Malignant Ovarian Clear Cell Tumor
Recurrent Ovarian Carcinoma
Interventions Drug: Epacadostat
Biological: Pembrolizumab
Enrollment 14
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Treatment (Epacadostat, Pembrolizumab)
Hide Arm/Group Description

Patients receive epacadostat PO BID and pembrolizumab IV over 30 minutes Q3W. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Epacadostat: Given PO (100 mg orally twice a day)

Pembrolizumab: Given IV (200 mg IV infusion over 30 minutes Q3W)

Period Title: Overall Study
Started 14
Completed 11
Not Completed 3
Reason Not Completed
Withdrawal by Subject             3
Arm/Group Title Treatment (Epacadostat, Pembrolizumab)
Hide Arm/Group Description

Patients receive epacadostat PO BID and pembrolizumab IV over 30 minutes Q3W. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Epacadostat: Given PO

Pembrolizumab: Given IV

Overall Number of Baseline Participants 14
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 14 participants
65  (11.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants
Female
14
 100.0%
Male
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants
Hispanic or Latino
1
   7.1%
Not Hispanic or Latino
13
  92.9%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
14
 100.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
1.Primary Outcome
Title Complete or Partial Objective Tumor Response
Hide Description Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version (v.) 1.1 criteria. Exact 95% confidence limits, accounting for interim analysis, will be provided in the final report. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=20% decrease in the sum of the longest diameter of target lesions and a 5 mm absolute increase; Overall Response (OR) = CR + PR.
Time Frame Within 7 months of study entry
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable patients
Arm/Group Title Treatment (Epacadostat, Pembrolizumab)
Hide Arm/Group Description:

Patients receive epacadostat PO BID and pembrolizumab IV over 30 minutes Q3W. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Epacadostat: Given PO

Pembrolizumab: Given IV

Overall Number of Participants Analyzed 14
Measure Type: Count of Participants
Unit of Measure: Participants
3
  21.4%
2.Secondary Outcome
Title Number of Participants With Adverse Events of Grade 3 or Higher
Hide Description Assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5. Number of participants with an adverse event of grade 3 or higher.
Time Frame Adverse events were assessed from the start of treatment until 30 days after the end of the last treatment cycle. Adverse events were collected for a median time of 5.1 months and a maximum time of 23.8 months.
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled patients.
Arm/Group Title Treatment (Epacadostat, Pembrolizumab)
Hide Arm/Group Description:

Patients receive epacadostat PO BID and pembrolizumab IV over 30 minutes Q3W. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Epacadostat: Given PO

Pembrolizumab: Given IV

Overall Number of Participants Analyzed 14
Measure Type: Count of Participants
Unit of Measure: Participants
9
  64.3%
3.Secondary Outcome
Title Progression-free Survival (PFS)
Hide Description Disease progression will be defined using RECIST v. 1.1 criteria. The distributions of PFS will be estimated and graphed using the Kaplan-Meier product limit method. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=20% decrease in the sum of the longest diameter of target lesions and a 5 mm absolute increase; Overall Response (OR) = CR + PR." Progression-free survival (PFS) is defined as the duration of time from the start of study treatment to time of progression or death, whichever occurs first.
Time Frame Radiographic tumor assessments were completed 12 weeks after the start of treatment, then every 6 weeks for 49 weeks, followed by every 12 weeks until disease progression or treatment discontinuation. The median follow-up time was 4.8 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable patients.
Arm/Group Title Treatment (Epacadostat, Pembrolizumab)
Hide Arm/Group Description:

Patients receive epacadostat PO BID and pembrolizumab IV over 30 minutes Q3W. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Epacadostat: Given PO

Pembrolizumab: Given IV

Overall Number of Participants Analyzed 14
Measure Type: Number
Unit of Measure: Participants with progression or death.
14
4.Secondary Outcome
Title Overall Survival (OS)
Hide Description Assessment of deaths starting from the time of enrollment.
Time Frame Overall survival (OS) is defined as the duration of time from the start of study treatment to time of death or the date of last contact. The median follow-up time for OS was 34.9 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable patients.
Arm/Group Title Treatment (Epacadostat, Pembrolizumab)
Hide Arm/Group Description:

Patients receive epacadostat PO BID and pembrolizumab IV over 30 minutes Q3W. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Epacadostat: Given PO

Pembrolizumab: Given IV

Overall Number of Participants Analyzed 14
Measure Type: Number
Unit of Measure: Patients who died.
9
5.Other Pre-specified Outcome
Title Ratio of Plasma Tryptophan to Kynurenine (T:K)
Hide Description Will determine whether the ratio of plasma T:K correlates with response to MK-3475 (pembrolizumab) and epacadostat, by evaluating plasma T:K pre-treatment, during treatment, and at disease progression. Pre-treatment levels of T:K ratio in plasma will be assessed for association with radiographic response to MK-3475 (pembrolizumab) and epacadostat. Changes between pre-treatment and post-cycle 1 and changes between post-cycle 1 and disease progression for T:K ratio will be evaluated with paired Student's T tests.
Time Frame Up to 5 years
Outcome Measure Data Not Reported
6.Other Pre-specified Outcome
Title Presence of PD-L1, IDO-1, Tumor-infiltrating Regulatory T Cells (Tregs), CD8 Tumor-infiltrating Lymphocytes (TILs), and Human Leukocyte Antigen (HLA) Class I in the Tumor Microenvironment
Hide Description Will determine whether the presence of PD-L1, IDO-1, Tregs, CD8 TILs, and HLA class I in the tumor microenvironment at baseline correlates with objective response to MK-3475 (pembrolizumab) + epacadostat. Baseline presence of PD-L1, IDO-1, Tregs, TILs, and HLA class I in the tumor microenvironment will also be assessed for correlation with radiographic response to MK-3475 (pembrolizumab) and epacadostat. Will consider logistic regression models for these analyses of continuous biomarkers, if appropriate given the number of responses and if exact tests of response for categorized levels of the biomarkers.
Time Frame Up to 5 years
Outcome Measure Data Not Reported
7.Other Pre-specified Outcome
Title Soluble PD-L1 (sPD-L1) Levels in Plasma
Hide Description Will determine whether sPD-L1 levels in plasma are correlated with response to MK-3475 (pembrolizumab) + epacadostat, by evaluating sPD-L1 concentrations pre-treatment, during treatment, and at disease progression. Pre-treatment levels of sPD-L1 in plasma will be assessed for association with radiographic response to MK-3475 (pembrolizumab) and epacadostat. Changes between pre-treatment and post-cycle 1 and changes between post-cycle 1 and disease progression for sPD-L1 will be evaluated with paired Student's T tests.
Time Frame Up to 5 years
Outcome Measure Data Not Reported
Time Frame Adverse events were assessed from the start of treatment until 30 days after the end of the last treatment cycle. Adverse events were assessed from the start of treatment until 30 days after the end of the last treatment cycle. Adverse events were collected for a median time of 5.1 months and a maximum time of 23.8 months. All-Cause mortality was monitored/assessed for a longer time period than Adverse events. All-Cause Mortality monitored/assessed for a median of 34.9 months.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Treatment (Epacadostat, Pembrolizumab)
Hide Arm/Group Description

Patients receive epacadostat PO BID and pembrolizumab IV over 30 minutes Q3W. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Epacadostat: Given PO

Pembrolizumab: Given IV

All-Cause Mortality
Treatment (Epacadostat, Pembrolizumab)
Affected / at Risk (%)
Total   9/14 (64.29%) 
Hide Serious Adverse Events
Treatment (Epacadostat, Pembrolizumab)
Affected / at Risk (%)
Total   7/14 (50.00%) 
Blood and lymphatic system disorders   
Anemia * 1  1/14 (7.14%) 
Gastrointestinal disorders   
Small Intestinal Obstruction * 1  1/14 (7.14%) 
Gastrointestinal Disorders - Other * 1  1/14 (7.14%) 
Ileal Obstruction * 1  1/14 (7.14%) 
General disorders   
Fatigue * 1  1/14 (7.14%) 
Death Nos * 1  2/14 (14.29%) 
Investigations   
Inr Increased * 1  1/14 (7.14%) 
Metabolism and nutrition disorders   
Hyponatremia * 1  1/14 (7.14%) 
Nervous system disorders   
Ataxia * 1  1/14 (7.14%) 
Respiratory, thoracic and mediastinal disorders   
Hypoxia * 1  1/14 (7.14%) 
1
Term from vocabulary, CTCAE (5.0)
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Treatment (Epacadostat, Pembrolizumab)
Affected / at Risk (%)
Total   14/14 (100.00%) 
Blood and lymphatic system disorders   
Disseminated Intravascular Coagulation * 1  1/14 (7.14%) 
Anemia * 1  7/14 (50.00%) 
Blood And Lymphatic System Disorders - Other * 1  1/14 (7.14%) 
Cardiac disorders   
Sinus Bradycardia * 1  1/14 (7.14%) 
Ear and labyrinth disorders   
Tinnitus * 1  1/14 (7.14%) 
Endocrine disorders   
Hyperthyroidism * 1  3/14 (21.43%) 
Hypothyroidism * 1  4/14 (28.57%) 
Eye disorders   
Blurred Vision * 1  1/14 (7.14%) 
Watering Eyes * 1  1/14 (7.14%) 
Gastrointestinal disorders   
Diarrhea * 1  4/14 (28.57%) 
Dry Mouth * 1  3/14 (21.43%) 
Constipation * 1  8/14 (57.14%) 
Colitis * 1  1/14 (7.14%) 
Vomiting * 1  7/14 (50.00%) 
Bloating * 1  1/14 (7.14%) 
Small Intestinal Obstruction * 1  3/14 (21.43%) 
Nausea * 1  9/14 (64.29%) 
Mucositis Oral * 1  2/14 (14.29%) 
Gastroesophageal Reflux Disease * 1  1/14 (7.14%) 
Gastrointestinal Disorders - Other * 1  1/14 (7.14%) 
Ascites * 1  1/14 (7.14%) 
Ileal Obstruction * 1  1/14 (7.14%) 
Abdominal Pain * 1  4/14 (28.57%) 
General disorders   
Pain * 1  2/14 (14.29%) 
Malaise * 1  1/14 (7.14%) 
Flu Like Symptoms * 1  1/14 (7.14%) 
Fever * 1  3/14 (21.43%) 
General Disorders And Administration Site Conditio * 1  1/14 (7.14%) 
Fatigue * 1  11/14 (78.57%) 
Edema Limbs * 1  3/14 (21.43%) 
Death Nos * 1  2/14 (14.29%) 
Chills * 1  2/14 (14.29%) 
Immune system disorders   
Allergic Reaction * 1  1/14 (7.14%) 
Infections and infestations   
Urinary Tract Infection * 1  1/14 (7.14%) 
Thrush * 1  2/14 (14.29%) 
Vaginal Infection * 1  1/14 (7.14%) 
Skin Infection * 1  1/14 (7.14%) 
Sinusitis * 1  1/14 (7.14%) 
Shingles * 1  1/14 (7.14%) 
Sepsis * 1  1/14 (7.14%) 
Conjunctivitis * 1  1/14 (7.14%) 
Bronchial Infection * 1  1/14 (7.14%) 
Injury, poisoning and procedural complications   
Fall * 1  1/14 (7.14%) 
Investigations   
Thyroid Stimulating Hormone Increased * 1  1/14 (7.14%) 
Platelet Count Decreased * 1  1/14 (7.14%) 
Lymphocyte Count Decreased * 1  1/14 (7.14%) 
Inr Increased * 1  2/14 (14.29%) 
Creatinine Increased * 1  3/14 (21.43%) 
Cholesterol High * 1  1/14 (7.14%) 
Cardiac Troponin I Increased * 1  1/14 (7.14%) 
Blood Bilirubin Increased * 1  1/14 (7.14%) 
White Blood Cell Decreased * 1  3/14 (21.43%) 
Alkaline Phosphatase Increased * 1  4/14 (28.57%) 
Alanine Aminotransferase Increased * 1  2/14 (14.29%) 
Activated Partial Thromboplastin Time Prolonged * 1  5/14 (35.71%) 
Metabolism and nutrition disorders   
Hypophosphatemia * 1  1/14 (7.14%) 
Hyponatremia * 1  3/14 (21.43%) 
Hypokalemia * 1  3/14 (21.43%) 
Hypocalcemia * 1  2/14 (14.29%) 
Hypoalbuminemia * 1  3/14 (21.43%) 
Hypomagnesemia * 1  2/14 (14.29%) 
Hyperkalemia * 1  1/14 (7.14%) 
Hyperglycemia * 1  5/14 (35.71%) 
Dehydration * 1  1/14 (7.14%) 
Anorexia * 1  7/14 (50.00%) 
Musculoskeletal and connective tissue disorders   
Back Pain * 1  1/14 (7.14%) 
Arthralgia * 1  1/14 (7.14%) 
Neck Pain * 1  1/14 (7.14%) 
Myalgia * 1  2/14 (14.29%) 
Muscle Cramp * 1  1/14 (7.14%) 
Joint Effusion * 1  1/14 (7.14%) 
Generalized Muscle Weakness * 1  1/14 (7.14%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Tumor Hemorrhage * 1  1/14 (7.14%) 
Nervous system disorders   
Seizure * 1  1/14 (7.14%) 
Peripheral Sensory Neuropathy * 1  1/14 (7.14%) 
Nervous System Disorders - Other * 1  2/14 (14.29%) 
Ischemia Cerebrovascular * 1  1/14 (7.14%) 
Headache * 1  2/14 (14.29%) 
Dysphasia * 1  1/14 (7.14%) 
Dysgeusia * 1  1/14 (7.14%) 
Dysarthria * 1  1/14 (7.14%) 
Dizziness * 1  2/14 (14.29%) 
Ataxia * 1  1/14 (7.14%) 
Psychiatric disorders   
Insomnia * 1  2/14 (14.29%) 
Depression * 1  1/14 (7.14%) 
Confusion * 1  1/14 (7.14%) 
Anxiety * 1  1/14 (7.14%) 
Agitation * 1  1/14 (7.14%) 
Renal and urinary disorders   
Urinary Incontinence * 1  1/14 (7.14%) 
Reproductive system and breast disorders   
Vaginal Hemorrhage * 1  1/14 (7.14%) 
Vaginal Discharge * 1  1/14 (7.14%) 
Pelvic Pain * 1  1/14 (7.14%) 
Respiratory, thoracic and mediastinal disorders   
Sore Throat * 1  1/14 (7.14%) 
Productive Cough * 1  1/14 (7.14%) 
Pleural Effusion * 1  1/14 (7.14%) 
Postnasal Drip * 1  1/14 (7.14%) 
Hypoxia * 1  1/14 (7.14%) 
Epistaxis * 1  1/14 (7.14%) 
Dyspnea * 1  3/14 (21.43%) 
Cough * 1  4/14 (28.57%) 
Wheezing * 1  1/14 (7.14%) 
Atelectasis * 1  1/14 (7.14%) 
Skin and subcutaneous tissue disorders   
Rash Maculo-Papular * 1  4/14 (28.57%) 
Rash Acneiform * 1  2/14 (14.29%) 
Pruritus * 1  1/14 (7.14%) 
Palmar-Plantar Erythrodysesthesia Syndrome * 1  1/14 (7.14%) 
Vascular disorders   
Hypertension * 1  1/14 (7.14%) 
Hot Flashes * 1  2/14 (14.29%) 
Flushing * 1  1/14 (7.14%) 
1
Term from vocabulary, CTCAE (5.0)
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Christopher Purdy on behalf of Danielle Enserro, PhD
Organization: NRG Oncology
Phone: (716) 845-1300 ext 2296
EMail: purdyc@nrgoncology.org
Layout table for additonal information
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT03602586    
Other Study ID Numbers: NCI-2018-01561
NCI-2018-01561 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
NRG-GY016 ( Other Identifier: NRG Oncology )
NRG-GY016 ( Other Identifier: CTEP )
U10CA180868 ( U.S. NIH Grant/Contract )
First Submitted: July 26, 2018
First Posted: July 27, 2018
Results First Submitted: July 14, 2022
Results First Posted: December 23, 2022
Last Update Posted: January 26, 2023