Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at UCLA
Dates
study started
estimated completion
Principal Investigator
by Lee Rosen, MD (ucla)

Description

Summary

RGX-202-001 is a Phase 1, first-in-human, dose escalation and expansion study of RGX-202-01 as a single agent and in combination with FOLFIRI +/- bevacizumab. RGX-202-01 is a small molecule inhibitor of the creatine transporter SLC6a8, a novel metabolic target that drives gastrointestinal cancer progression. During the dose escalation stage, multiple doses of orally administered RGX-202-01 with or without FOLFIRI +/- bevacizumab (single agent or combination therapy) will be evaluated in patients with advanced gastrointestinal tumors (i.e., locally advanced and unresectable, or metastatic) who have had PD on available standard systemic therapies or for which there are no standard systemic therapies of relevant clinical impact. In the expansion stage: Patients with colorectal cancer (CRC) RAS Mutant will be treated at the optimal dose.

Official Title

A Phase 1 Study of RGX-202-01, a Small Molecule Inhibitor of the Creatine Transporter SLC6a8, as a Single Agent and as Combination Therapy in Patients With Advanced Gastrointestinal Malignancies With Select Expansion Cohorts

Keywords

Gastrointestinal Cancer Gastrointestinal Neoplasms Colorectal Cancer Colorectal Neoplasms Colorectal Carcinoma Gastric Cancer Gastric Neoplasm KRAS Mutation-Related Tumors CRC Colorectal Cancer Metastatic SLC6a8 Creatine transporter FOLFIRI KRAS NRAS RAS Neoplasms Stomach Neoplasms Digestive System Neoplasms Bevacizumab RGX-202-01 Expansion: 2nd Line Colorectal Cancer (CRC) KRAS (+)

Eligibility

You can join if…

Open to people ages 18 years and up

  • The patient must have histologic or cytologic evidence of a RAS colorectal cancer of adenocarcinoma or poorly differentiated 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 or if such therapy has been refused by the patient.
  • 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).
  • Pathologically documented adenocarcinoma or poorly differentiated locally advanced/metastatic colorectal cancer
  • Have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as assessed by the Investigator
  • Adults ≥18 years
  • Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to 1
  • Adequate cardiac function, as defined by left ventricular ejection fraction (LVEF) ≥45%
  • Adequate organ function
  • Prothrombin time ≤1.5 x ULN or international normalized ratio within ≤1.5; and either partial thromboplastin time or activated partial thromboplastin time ≤1.5 x ULN. Patients on warfarin may be included if on a stable dose with a therapeutic INR <3.5

Inclusion Criteria for RGX-202-01 plus FOLFIRI and bevacizumab expansion stages:

For the expansion stage only, patients must have a tumor that is laboratory-confirmed to be RAS mutant.

  • Must have received only one prior standard of care oxaliplatin-containing regimen for locally advanced/metastatic colorectal cancer (CRC)
  • Must have received prior treatment with pembrolizumab or an FDA approved PD-1/L1 inhibitor as well, if the patient has dMMR/MSI-H colorectal cancer
  • May have received prior treatment with bevacizumab, cetuximab, or panitumumab, or an FDA approved biosimilar.

You CAN'T join if...

  • Unresolved Grade > 2 toxicities from prior anticancer therapy; excluding Grade 2 chemotherapy-related neuropathy, alopecia; and excluding Grade 2-3 asymptomatic laboratory abnormalities if considered clinically insignificant by the Investigator, or can be managed with available medical therapies
  • Has malignancy of small cell, neuroendocrine, or squamous histology
  • Unable to meet the requirement of an adequate treatment washout period before enrollment
  • Has additional malignancy that may confound the assessment of study endpoints. Participants with 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 are not excluded
  • Has clinically significant cardiovascular disease (New York Heart Association Class III or IV congestive heart failure, history of myocardial infarction, uncontrolled angina, unstable angina or stroke within 6 months before enrollment, uncontrolled hypertension or clinically significant arrhythmias not controlled by medication
  • Has clinically active brain or leptomeningeal metastases
  • 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
  • Pregnant or breast feeding
  • Has an ongoing chronic hepatopathy of any origin
  • Has an evidence of muscular dystrophies or ongoing muscle pathology
  • Has oxygen-support requirements
  • Has corrected QT interval (QTc) prolongation to >470 ms (females) or >450 ms (males)
  • Has a physical abnormality or medical condition that limits swallowing multiple pills or has a history of non-adherence to oral therapies
  • Has a malabsorption condition, such as short bowel syndrome, impaired GI function or GI disease that may significantly alter absorption, or a high likelihood of impending bowel obstruction, such as strictures
  • Has clinically significant ascites (i.e. requiring paracentesis within the preceding 28 days or treatment with pain medication)
  • Has a medical condition which, in the opinion of the Investigator, places the patient at an unacceptably high risk for toxicities

Exclusion Criteria for RGX-202-01 plus FOLFIRI and bevacizumab dose escalation and expansion stages:

  • Has known dihydropyrimidine dehydrogenase (DPD) deficiency or is on treatment with DPD inhibitors, including sorivudine or its chemically related analogues such as brivudine, within 4 weeks prior to the start of treatment
  • Has known homozygous or heterozygous for UGT1A128, UGT1A16, UGT1A9*1 or ABCG2 allele

  • Require treatment with strong CYP3A4 inhibitors or strong UGT1A1 inhibitors
  • Previously treated with FOLFIRI or other irinotecan containing regimens
  • Has proteinuria ≥ 2gm/24 and/or nephrotic syndrome. Patients with a proteinuria 2+ or greater urine dipstick reading should undergo further assessment, e.g., a 24-hour urine collection
  • History of acute or subacute intestinal occlusion - except if such an event occurred only around the time of diagnosis - or chronic inflammatory bowel disease or chronic diarrhea
  • History of severe, non-healing wounds, ulcers or bone fractures
  • History of arterial thromboemboli or severe hemorrhage within 6 months of prior FOLFIRI treatment with an exception of tumor bleeding before tumor resection surgery
  • History of hemorrhagic diathesis or tendency towards thrombosis

Locations

  • UCLA Department of Medicine accepting new patients
    Santa Monica California 90404 United States
  • Cedars-Sinai Medical Center accepting new patients
    Los Angeles California 90048 United States
  • City of Hope terminated
    Duarte California 91010 United States

Lead Scientist at UC Cancer

  • Lee Rosen, MD (ucla)
    HS Clinical Professor, Medicine. Authored (or co-authored) 109 research publications

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Inspirna, Inc.
ID
NCT03597581
Phase
Phase 1 research study
Study Type
Interventional
Participants
Expecting 60 study participants
Last Updated