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

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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

View this study on Beta.ClinicalTrials.gov

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

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Treatment (Epacadostat, Pembrolizumab)
Arm/Group Description	Patients receive epacadostat PO BID...
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

Baseline Characteristics

Arm/Group Title		Treatment (Epacadostat, Pembrolizumab)
Arm/Group Description		Patients receive epacadostat PO BID...
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
Baseline Analysis Population Description		[Not Specified]
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%

Outcome Measures

1.Primary Outcome


Title	Complete or Partial Objective Tumor Response
Description	Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) vers...
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

Outcome Measure Data

Analysis Population Description

Evaluable patients


Arm/Group Title	Treatment (Epacadostat, Pembrolizumab)
Arm/Group Description:	Patients receive epacadostat PO BID...
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
Description	Assessed using Common Terminology Criteria for Adverse Events (CTCAE) ...
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.

Outcome Measure Data

Analysis Population Description

All enrolled patients.


Arm/Group Title	Treatment (Epacadostat, Pembrolizumab)
Arm/Group Description:	Patients receive epacadostat PO BID...
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)
Description	Disease progression will be defined using RECIST v. 1.1 criteria. The ...
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.

Outcome Measure Data

Analysis Population Description

Evaluable patients.


Arm/Group Title	Treatment (Epacadostat, Pembrolizumab)
Arm/Group Description:	Patients receive epacadostat PO BID...
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)
Description	Assessment of deaths starting from the time of enrollment.
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.

Outcome Measure Data

Analysis Population Description

Evaluable patients.


Arm/Group Title	Treatment (Epacadostat, Pembrolizumab)
Arm/Group Description:	Patients receive epacadostat PO BID...
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)
Description	Will determine whether the ratio of plasma T:K correlates with respons...
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
Description	Will determine whether the presence of PD-L1, IDO-1, Tregs, CD8 TILs, ...
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
Description	Will determine whether sPD-L1 levels in plasma are correlated with res...
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

Adverse Events

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)
Arm/Group Description	Patients receive epacadostat PO BID...
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%)
Serious Adverse Events 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
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

Limitations and Caveats

[Not Specified]

More Information

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

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