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A Study of RGX-104 in Patients With Advanced Solid Malignancies and Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2017 by Rgenix, Inc.
Sponsor:
Information provided by (Responsible Party):
Rgenix, Inc.
ClinicalTrials.gov Identifier:
NCT02922764
First received: September 29, 2016
Last updated: April 12, 2017
Last verified: April 2017
  Purpose

Study RGX-104-001 is a Phase 1, first-in-human, dose escalation and expansion study of RGX-104, an oral small molecule targeting the liver X receptor (LXR). RGX-104 activates LXR, resulting in depletion of both myeloid-derived suppressor cells (MDSCs) as well as tumor blood vessels. MDSCs block the ability of T-cells and other cells of the immune system from attacking tumors.

During the dose escalation stage, multiple doses and schedules of orally administered RGX-104 will be evaluated in patients with advanced solid tumors and lymphoma (i.e., locally advanced and unresectable, or metastatic) who have had progressive disease (PD) on available standard systemic therapies or for which there are no standard systemic therapies of relevant impact. In the expansion stage of the study, additional patients with melanoma, non-small cell lung cancer, epithelial ovarian carcinoma, or breast cancer will be treated at the MTD (or maximum tested dose if no MTD is identified, or dose below the MTD if there is evidence suggesting a more favorable risk/benefit profile) to provide further characterization of RGX-104 safety, efficacy, PK, and pharmacodynamics, including biomarkers of immunologic activity and LXR target activation.


Condition Intervention Phase
Malignant Neoplasms
Drug: RGX-104
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase 1 Study of RGX-104, a Small Molecule LXR Agonist, in Patients With Advanced Solid Malignancies and Lymphoma With an Expansion in Select Malignancies

Resource links provided by NLM:


Further study details as provided by Rgenix, Inc.:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD), or the maximum tested dose at which multiple dose-limiting toxicities (DLTs) are not observed, of RGX-104. [ Time Frame: 6 months ]
  • Overall response rate associated with RGX-104 treatment. [ Time Frame: 24 months ]
  • Progression-free survival associated with RGX-104 treatment. [ Time Frame: 24 months ]
  • Number of participants with treatment-emergent adverse events with severity as determined by CTCAE v4.03. [ Time Frame: 24 months ]

Secondary Outcome Measures:
  • Pharmacokinetics: Maximum Plasma Concentration (Cmax) of RGX-104. [ Time Frame: 24 months ]
  • Pharmacokinetics: Area Under the Curve (AUC) of RGX-104. [ Time Frame: 24 months ]

Estimated Enrollment: 80
Study Start Date: November 2016
Estimated Study Completion Date: October 2019
Estimated Primary Completion Date: October 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: RGX-104
RGX-104 is a small molecule agonist of the liver X receptor (LXR), a member of the nuclear receptor family of transcription factors.
Drug: RGX-104

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. The patient must have histologic or cytologic evidence of a malignant solid tumor or lymphoma (any histology) and must have disease that is resistant to or relapsed following available standard systemic therapy, or for which there is no standard systemic therapy or reasonable therapy likely to result in clinical benefit.
  2. The patient must have advanced disease, defined as cancer that is either metastatic or locally advanced and unresectable (and for which additional radiation therapy or other locoregional therapies are not considered feasible).
  3. The patient must have disease that is measurable by standard imaging techniques (excluding patients with prostate cancer with PSA > 2 and bone disease documented by bone scan or other imaging), per immune-related response criteria (irRC; all tumor types except lymphoma) or International Working Group (IWG) revised response criteria for malignant lymphoma (lymphoma only). For patients with prior radiation therapy, measurable lesions must be outside of any prior radiation field(s), unless disease progression has been documented at that disease site subsequent to radiation.
  4. The patient is ≥18 years old.
  5. The patient has an ECOG PS of ≤1.
  6. The patient has adequate baseline organ function, as demonstrated by the following:

    • Serum creatinine ≤1.5 times institutional upper limit of normal (ULN) or calculated creatinine clearance >30 mL/min;
    • Serum albumin ≥2.5 g/dl;
    • Bilirubin ≤1.5 times institutional ULN;
    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 times institutional ULN (patients with hepatic metastases must have AST/ALT ≤5 times ULN);
    • For patients not taking warfarin: international normalized ratio (INR) ≤1.5 or prothrombin time (PT) ≤1.5 times ULN; and either partial thromboplastin time or activated partial thromboplastin time (PTT or aPTT) ≤1.5 times ULN. For patients taking warfarin: INR <3.5.
  7. The patient has adequate baseline hematologic function, as demonstrated by the following:

    • Absolute neutrophil count (ANC) ≥1.5x10^9/L
    • Hemoglobin ≥8 g/dL and no red blood cell (RBC) transfusions during the prior 14 days
    • Platelet count ≥100x10^9/L and no platelet transfusions during the prior 14 days
  8. The patient has a normal left ventricular ejection fraction (LVEF) per institutional criteria as determined by either echocardiography (ECHO) or multigated acquisition (MUGA) scanning.
  9. If the patient is a woman of child bearing potential (WOCBP), she has had a negative serum or urine pregnancy test within 2 weeks prior to treatment.
  10. The patient (male and female) agrees to use acceptable contraceptive methods for the duration of time on the study, and continue to use acceptable contraceptive methods for 1 month after the last treatment with RGX-104.
  11. The patient has signed informed consent prior to initiation of any study-specific procedures or treatment.
  12. The patient is able to adhere to the study visit schedule and other protocol requirements, including follow-up for survival assessment.
  13. Tumor tissue (a minimum of 5 and up to 10 unstained slides, or paraffin block), ideally from the patient's most recent biopsy, must be delivered from the patient's local institution to the site prior to treatment with RGX-104.

Exclusion Criteria:

  1. The patient has persistent clinically significant toxicities (Grade ≥2) from previous anticancer therapy (excluding Grade 2 chemotherapy-related neuropathy and alopecia which are permitted, and excluding Grade 2-3 laboratory abnormalities if they are not associated with symptoms, are not considered clinically significant by the Investigator, and can be managed with available medical therapies).
  2. The patient has received treatment with chemotherapy, external-beam radiation, or other systemic anticancer therapy within 14 days prior to RGX-104 administration (42 days for prior nitrosourea or mitomycin-C; patients with advanced prostate cancer who are receiving luteinizing hormone releasing hormone (LHRH) agonists are permitted onto the study and should continue use of these agents during study treatment).
  3. The patient has received treatment with an investigational systemic anticancer agent within 14 days prior to RGX-104 administration.
  4. The patient has previously received treatment with RGX-104 or another investigational agent that is a known LXR agonist.
  5. The patient has an additional active malignancy that may confound the assessment of the study endpoints. Patients with a past cancer history (active malignancy within 2 years prior to study entry) with substantial potential for recurrence must be discussed with the Sponsor before study entry. Patients with the following concomitant neoplastic diagnoses are eligible: non-melanoma skin cancer, carcinoma in situ (including transitional cell carcinoma, cervical intraepithelial neoplasia, and melanoma in situ), organ-confined prostate cancer with no evidence of progressive disease.
  6. The patient has clinically significant cardiovascular disease (e.g., uncontrolled or any New York Heart Association Class 3 or 4 congestive heart failure, uncontrolled angina, history of myocardial infarction, unstable angina or stroke within 6 months prior to study entry, uncontrolled hypertension or clinically significant arrhythmias not controlled by medication).
  7. The patient has uncontrolled, clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease, pulmonary hypertension) that in the opinion of the Investigator would put the patient at significant risk for pulmonary complications during the study.
  8. The patient has known active or suspected brain or leptomeningeal metastases (central nervous system [CNS] imaging is not required prior to study entry unless there is a clinical suspicion of CNS involvement). Patients with stable, treated brain metastases are eligible provided there is no evidence of CNS disease growth on imaging for at least 2 months following radiation therapy or other locoregional ablative therapy to the CNS.
  9. The patient has a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to RGX-104 administration. Inhaled or topical steroids and adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
  10. The patient has uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, disseminated intravascular coagulation, or psychiatric illness/social situations that would limit compliance with study requirements.
  11. The patient is pregnant or breast feeding.
  12. The patient has known positive status for human immunodeficiency virus active or chronic Hepatitis B or Hepatitis C.
  13. The patient is oxygen-dependent.
  14. The patient has a history of pancreatitis.
  15. The patient has Grade ≥2 hypercholesterolemia (total cholesterol >300 mg/dL or >7.75 mmol/L) and/or hypertriglyceridemia (triglyceride >300 mg/dL or ≥3.42 mmol/L) in the fasting state.
  16. QTcF >450 msec (males) or >470 msec (females).
  17. The patient has a cataract of Grade ≥2 for posterior subcapsular cataract, cortical cataract, nuclear opalescence, or nuclear color based on the Lens Opacities Classification System III (LOCS III).
  18. The patient requires statin (e.g., rosuvastatin, atorvastatin, etc.) therapy.
  19. The patient requires treatment with a medication that is a strong inhibitor of CYP3A4 (boceprevir, clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, or voriconazole).
  20. The patient requires treatment with a pH elevating agent, including H2 blockers, proton pump inhibitors, and antacids. If the medication is considered to be medically necessary, the patient should be discussed with the Medical Monitor.
  21. The patient has any medical condition which in the opinion of the Investigator places the patient at an unacceptably high risk for toxicities.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02922764

Contacts
Contact: Michael Szarek, PhD 646-856-9261 trials@rgenix.com

Locations
United States, California
Cedars-Sinai Medical Center Recruiting
Los Angeles, California, United States, 90048
Contact: Monica Mita, MD    310-248-6729    Monica.Mita@cshs.org   
University of California, Los Angeles Recruiting
Los Angeles, California, United States, 90095
Contact: Bartosz Chmielowski, MD, PhD    310-586-2650    BChmielowski@mednet.ucla.edu   
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Michael Postow, MD    646-888-4589    postowm@mskcc.org   
United States, Tennessee
The Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact: Erika Hamilton, MD    615-329-7274    ehamilton@tnonc.com   
United States, Texas
The University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Shubham Pant, MD    713-563-0181    SPant@mdanderson.org   
Sponsors and Collaborators
Rgenix, Inc.
  More Information

Responsible Party: Rgenix, Inc.
ClinicalTrials.gov Identifier: NCT02922764     History of Changes
Other Study ID Numbers: RGX-104-001
Study First Received: September 29, 2016
Last Updated: April 12, 2017
Individual Participant Data  
Plan to Share IPD: Undecided

Keywords provided by Rgenix, Inc.:
Solid malignancy
Lymphoma
Solid tumor
Melanoma
Non-small cell lung cancer
Epithelial ovarian carcinoma
Breast cancer
NSCLC
EOC
BC
LXR
ApoE
mBC

Additional relevant MeSH terms:
Lymphoma
Neoplasms
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on May 23, 2017