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Addition of X4P-001 to Nivolumab Treatment in Participants With Renal Cell Carcinoma

Primary Purpose

Clear Cell Renal Cell Carcinoma

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

X4P-001

Nivolumab

About this trial

This is an interventional treatment trial for Clear Cell Renal Cell Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Histologically confirmed diagnosis of Renal Cell Carcinoma with a documented clear cell component (ccRCC).
Currently receiving nivolumab and considered by Investigator to have the potential to derive clinical benefit from continuing treatment with nivolumab.
Based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria on current nivolumab treatment (prior to initiation of this study), has a best response of confirmed stable disease (SD) or confirmed progressive disease (PD). Confirmed SD or confirmed PD refers to a response that is confirmed by a second scan which is at least 4 weeks apart from the previous scan.
At least one extra-renal measurable target lesion meeting the criteria of RECIST Version 1.1.
Agree to use contraception from screening, through the study, and for at least 5 months after the last dose of nivolumab as follows: for women of childbearing potential agree to use highly-effective contraceptive methods; for males, agree to use a condom with sexual partner.

Exclusion Criteria:

Pregnant or nursing.
Life expectancy of less than 3 months.
Performance status greater than or equal to (≥) 2 (Eastern Cooperative Oncology Group [ECOG] criteria).
New York Heart Association (NYHA) Class III or IV, uncontrolled hypertension, or clinically significant arrhythmia.
Previously received X4P-001.
Has a second malignancy. Except: malignancies that were treated curatively and have not recurred within 2 years prior to study treatment; completely resected basal cell and squamous cell skin cancers; any malignancy considered to be indolent and that has never required therapy; and completely resected carcinoma in situ of any type.
Has active central nervous system (CNS) metastases (including evidence of cerebral edema by Magnetic Resonance Imaging [MRI], or progression from prior imaging study, or any requirement for steroids, or clinical symptoms of/from CNS metastases) within 28 days prior to study treatment. Subjects with known CNS metastases must have a baseline MRI scan within 28 days of study treatment.
Ongoing clinical adverse events National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade greater than (>) 2 resulting from prior cancer therapies.
Known history of Human Immunodeficiency Virus (HIV) or Acquired Immunodeficiency Syndrome (AIDS); or positive test for hepatitis C virus (HCV), or hepatitis B surface antigen (HBsAg).
History of clinically significant or uncontrolled cardiac, hepatic, or pulmonary disease.
Has had within the past 6 months the occurrence of one or more of the following events: myocardial infarction, cerebrovascular accident, deep vein thrombosis, pulmonary embolism, hemorrhage (NCI CTCAE Grade 3 or 4), chronic liver disease (meeting criteria for Child-Pugh Class B or C), or organ transplantation.
Inadequate hematologic, hepatic, or renal function.

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

X4P-001 Plus Nivolumab

Arm Description

Participants will receive X4P-001 400 milligrams (mg) (as 4 capsules of 100 mg each) orally once daily in combination with nivolumab 240 mg intravenous (IV) infusion (over 60 minutes) every 2 weeks. Study medication will be administered in 28-day cycles and will continue until treatment-limiting toxicity or disease progression.

Outcomes

Primary Outcome Measures

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Drug-related TEAEs: TEAEs with possible, probable, definite, or missing relationship to study medication (X4P-001 or Nivolumab). Serious AEs: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. TEAEs were defined as events occurring on or after the first dose of study drug through 30 days after the last dose. Any TEAEs included both serious and non-serious TEAEs. A summary of other non-serious AEs and all serious AEs, regardless of causality, is located in Reported AE section.

Secondary Outcome Measures

Maximum Observed Plasma Concentration (Cmax) of X4P-001

Samples were to be analyzed for X4P-001 concentration using reversed-phase high performance liquid chromatography (RP-HPLC) with tandem mass spectrometry (MS) detection.

Area Under the Plasma Concentration Versus Time Curve (AUC) of X4P-001

Samples were to be analyzed for X4P-001 concentration using RP-HPLC with tandem MS detection.

Minimum Plasma Concentration (Cmin) of X4P-001

Samples were to be analyzed for X4P-001 concentration using RP-HPLC with tandem MS detection.

Time to Reach Cmax (Tmax) of X4P-001

Samples were to be analyzed for X4P-001 concentration using RP-HPLC with tandem MS detection.

Objective Response Rate (ORR): Percentage of Participants With Objective Response, Evaluated Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

ORR was defined as percentage of participants with best overall response of complete response (CR) or partial response (PR). CR: Disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) with a reduction in short axis to less than (<) 10 millimeters (mm). PR: At least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Duration of Objective Response (DOR), Evaluated Using RECIST Version 1.1

DOR was defined as the time from first CR or PR whichever comes first until the time of disease progression by RECIST v1.1 or death due to any cause. CR: Disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) with a reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Disease progression: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum also demonstrated an absolute increase of at least 5 mm. Unequivocal progression of existing non-target lesions. The appearance of 1 or more new lesions was also considered progression.

Time to Objective Response, Evaluated Using RECIST Version 1.1

Time to objective response was defined as time from first administration of combination regimen to first CR or PR whichever comes first. CR: Disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) with a reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Disease Control Rate: Percentage of Participants With CR or PR or Stable Disease (SD), Evaluated Using RECIST Version 1.1

Disease control rate was defined as percentage of participants with best overall response of CR or PR or SD. CR: Disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) with a reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study In addition to the relative increase of 20%, the sum also demonstrated an absolute increase of at least 5 mm. Unequivocal progression of existing non-target lesions. The appearance of 1 or more new lesions was also considered progression.

Progression Free Survival (PFS), Evaluated Using RECIST Version 1.1

PFS was defined as the time from first administration of study medication until objective tumor progression or death from any cause. Tumor progression: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study In addition to the relative increase of 20%, the sum also demonstrated an absolute increase of at least 5 mm. An unequivocal progression of existing non-target lesions or the appearance of 1 or more new lesions was also considered progression.

Time to Progression (TTP), Evaluated Using RECIST Version 1.1

TTP was defined as the time from first administration of study medication until objective tumor progression. Tumor progression: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study In addition to the relative increase of 20%, the sum also demonstrated an absolute increase of at least 5 mm. Unequivocal progression of existing non-target lesions or the appearance of 1 or more new lesions was also considered progression.

Full Information

NCT ID

NCT02923531

First Posted

September 30, 2016

Last Updated

November 30, 2022

Sponsor

X4 Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT02923531

Brief Title

Addition of X4P-001 to Nivolumab Treatment in Participants With Renal Cell Carcinoma

Official Title

A Phase 1B/2A Trial Adding X4P-001 in Patients Receiving Nivolumab for Treatment of Advanced Clear Cell Renal Cell Carcinoma

Study Type

Interventional

2. Study Status

Record Verification Date

November 2022

Overall Recruitment Status

Terminated

Why Stopped

Due to low enrollment, the study was terminated early.

Study Start Date

December 7, 2016 (Actual)

Primary Completion Date

August 8, 2018 (Actual)

Study Completion Date

August 8, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

X4 Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

The purpose of this study is to determine if the combination of X4P-001 plus nivolumab is safe and tolerable. Secondly, the study will investigate if adding X4P-001 to nivolumab treatment has an effect on the body and the cancer tumor, in participants receiving nivolumab but not exhibiting a radiological response.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Clear Cell Renal Cell Carcinoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

9 (Actual)

8. Arms, Groups, and Interventions

Arm Title

X4P-001 Plus Nivolumab

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

X4P-001

Intervention Description

X4P-001 will be administered as per the dose and schedule specified in the arm.

Intervention Type

Drug

Intervention Name(s)

Nivolumab

Other Intervention Name(s)

Opdivo

Intervention Description

Nivolumab will be administered as per the dose and schedule specified in the arm.

Primary Outcome Measure Information:

Title

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

Description

Time Frame

From administration of first dose of study medication (Day 1) up to 30 days after last dose (up to 16 months)

Secondary Outcome Measure Information:

Title

Maximum Observed Plasma Concentration (Cmax) of X4P-001

Description

Samples were to be analyzed for X4P-001 concentration using reversed-phase high performance liquid chromatography (RP-HPLC) with tandem mass spectrometry (MS) detection.

Time Frame

Predose (-30 minutes) on Day 1 of Cycle 1; predose (-10 minutes) on Days 8, 15, and 22 of Cycle 1, and Day 1 of Cycle 3; postdose at 60 and 90 minutes, and 2, 3 4, and 8 hours on Day 22 of Cycle 1

Title

Area Under the Plasma Concentration Versus Time Curve (AUC) of X4P-001

Description

Samples were to be analyzed for X4P-001 concentration using RP-HPLC with tandem MS detection.

Time Frame

Predose (-30 minutes) on Day 1 of Cycle 1; predose (-10 minutes) on Days 8, 15, and 22 of Cycle 1, and Day 1 of Cycle 3; postdose at 60 and 90 minutes, and 2, 3 4, and 8 hours on Day 22 of Cycle 1

Title

Minimum Plasma Concentration (Cmin) of X4P-001

Description

Samples were to be analyzed for X4P-001 concentration using RP-HPLC with tandem MS detection.

Time Frame

Predose (-30 minutes) on Day 1 of Cycle 1; predose (-10 minutes) on Days 8, 15, and 22 of Cycle 1, and Day 1 of Cycle 3; postdose at 60 and 90 minutes, and 2, 3 4, and 8 hours on Day 22 of Cycle 1

Title

Time to Reach Cmax (Tmax) of X4P-001

Description

Samples were to be analyzed for X4P-001 concentration using RP-HPLC with tandem MS detection.

Time Frame

Predose (-30 minutes) on Day 1 of Cycle 1; predose (-10 minutes) on Days 8, 15, and 22 of Cycle 1, and Day 1 of Cycle 3; postdose at 60 and 90 minutes, and 2, 3 4, and 8 hours on Day 22 of Cycle 1

Title

Objective Response Rate (ORR): Percentage of Participants With Objective Response, Evaluated Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

Description

Time Frame

From administration of first dose of study medication (Day 1) until disease progression, study completion or early termination (up to 15 months)

Title

Duration of Objective Response (DOR), Evaluated Using RECIST Version 1.1

Description

Time Frame

Time from first CR or PR until the time of disease progression or death due to any cause (up to 15 months)

Title

Time to Objective Response, Evaluated Using RECIST Version 1.1

Description

Time Frame

From administration of first dose of study medication (Day 1) until first appearance of CR or PR (up to 15 months)

Title

Disease Control Rate: Percentage of Participants With CR or PR or Stable Disease (SD), Evaluated Using RECIST Version 1.1

Description

Time Frame

From administration of first dose of study medication (Day 1) until disease progression, study completion or early termination (up to 15 months)

Title

Progression Free Survival (PFS), Evaluated Using RECIST Version 1.1

Description

Time Frame

From administration of first dose of study medication (Day 1) until disease progression or death from any cause (up to 15 months)

Title

Time to Progression (TTP), Evaluated Using RECIST Version 1.1

Description

Time Frame

From administration of first dose of study medication (Day 1) until disease progression (up to 15 months)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Histologically confirmed diagnosis of Renal Cell Carcinoma with a documented clear cell component (ccRCC). Currently receiving nivolumab and considered by Investigator to have the potential to derive clinical benefit from continuing treatment with nivolumab. Based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria on current nivolumab treatment (prior to initiation of this study), has a best response of confirmed stable disease (SD) or confirmed progressive disease (PD). Confirmed SD or confirmed PD refers to a response that is confirmed by a second scan which is at least 4 weeks apart from the previous scan. At least one extra-renal measurable target lesion meeting the criteria of RECIST Version 1.1. Agree to use contraception from screening, through the study, and for at least 5 months after the last dose of nivolumab as follows: for women of childbearing potential agree to use highly-effective contraceptive methods; for males, agree to use a condom with sexual partner. Exclusion Criteria: Pregnant or nursing. Life expectancy of less than 3 months. Performance status greater than or equal to (≥) 2 (Eastern Cooperative Oncology Group [ECOG] criteria). New York Heart Association (NYHA) Class III or IV, uncontrolled hypertension, or clinically significant arrhythmia. Previously received X4P-001. Has a second malignancy. Except: malignancies that were treated curatively and have not recurred within 2 years prior to study treatment; completely resected basal cell and squamous cell skin cancers; any malignancy considered to be indolent and that has never required therapy; and completely resected carcinoma in situ of any type. Has active central nervous system (CNS) metastases (including evidence of cerebral edema by Magnetic Resonance Imaging [MRI], or progression from prior imaging study, or any requirement for steroids, or clinical symptoms of/from CNS metastases) within 28 days prior to study treatment. Subjects with known CNS metastases must have a baseline MRI scan within 28 days of study treatment. Ongoing clinical adverse events National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade greater than (>) 2 resulting from prior cancer therapies. Known history of Human Immunodeficiency Virus (HIV) or Acquired Immunodeficiency Syndrome (AIDS); or positive test for hepatitis C virus (HCV), or hepatitis B surface antigen (HBsAg). History of clinically significant or uncontrolled cardiac, hepatic, or pulmonary disease. Has had within the past 6 months the occurrence of one or more of the following events: myocardial infarction, cerebrovascular accident, deep vein thrombosis, pulmonary embolism, hemorrhage (NCI CTCAE Grade 3 or 4), chronic liver disease (meeting criteria for Child-Pugh Class B or C), or organ transplantation. Inadequate hematologic, hepatic, or renal function.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Chief Medical Officer

Organizational Affiliation

X4 Pharmaceuticals, Inc.

Official's Role

Study Director

Facility Information:

City

Washington

State/Province

District of Columbia

Country

United States

City

Boston

State/Province

Massachusetts

Country

United States

City

Hackensack

State/Province

New Jersey

Country

United States

City

Chapel Hill

State/Province

North Carolina

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

33507454

Citation

Choueiri TK, Atkins MB, Rose TL, Alter RS, Ju Y, Niland K, Wang Y, Arbeit R, Parasuraman S, Gan L, McDermott DF. A phase 1b trial of the CXCR4 inhibitor mavorixafor and nivolumab in advanced renal cell carcinoma patients with no prior response to nivolumab monotherapy. Invest New Drugs. 2021 Aug;39(4):1019-1027. doi: 10.1007/s10637-020-01058-2. Epub 2021 Jan 28.

Results Reference

derived

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Addition of X4P-001 to Nivolumab Treatment in Participants With Renal Cell Carcinoma

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