Clinical trial NCT02923531: 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
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Clear Cell Renal Cell Carcinoma
Lead sponsor: X4 Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2016-10-04
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From administration of first dose of study medication (Day 1) up to 30 days after last dose (up to 16 months)
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of X4P-001
timeFrame: 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
measure: Area Under the Plasma Concentration Versus Time Curve (AUC) of X4P-001
timeFrame: 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
measure: Minimum Plasma Concentration (Cmin) of X4P-001
timeFrame: 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
measure: Time to Reach Cmax (Tmax) of X4P-001
timeFrame: 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
measure: Objective Response Rate (ORR): Percentage of Participants With Objective Response, Evaluated Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
timeFrame: From administration of first dose of study medication (Day 1) until disease progression, study completion or early termination (up to 15 months)
measure: Duration of Objective Response (DOR), Evaluated Using RECIST Version 1.1
timeFrame: Time from first CR or PR until the time of disease progression or death due to any cause (up to 15 months)
measure: Time to Objective Response, Evaluated Using RECIST Version 1.1
timeFrame: From administration of first dose of study medication (Day 1) until first appearance of CR or PR (up to 15 months)
measure: Disease Control Rate: Percentage of Participants With CR or PR or Stable Disease (SD), Evaluated Using RECIST Version 1.1
timeFrame: From administration of first dose of study medication (Day 1) until disease progression, study completion or early termination (up to 15 months)
measure: Progression Free Survival (PFS), Evaluated Using RECIST Version 1.1
timeFrame: From administration of first dose of study medication (Day 1) until disease progression or death from any cause (up to 15 months)
measure: Time to Progression (TTP), Evaluated Using RECIST Version 1.1
timeFrame: From administration of first dose of study medication (Day 1) until disease progression (up to 15 months)
Other outcomes:
Locations:
city: Washington
country: United States
state: District of Columbia
city: Boston
country: United States
state: Massachusetts
city: Hackensack
country: United States
state: New Jersey
city: Chapel Hill
country: United States
state: North Carolina
Study officials:
affiliation: X4 Pharmaceuticals, Inc.
name: Chief Medical Officer
role: STUDY_DIRECTOR
References:
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.