RGX-202-01 With or Without FOLFIRI in Advanced Gastrointestinal Malignancies

What is the Purpose of this Study?

This study focuses on patients who have an advanced cancer for which further treatment is recommended, but standard (non-research) treatment is no longer effective. The study will evaluate an investigational drug called RGX-202-01. It is hoped that by taking RGX-202-01, alone or in combination with a chemotherapy regimen called FOLFIRI (chemotherapy drugs approved by the U.S. Food and Drug Administration), the growth of the patient’s tumor will be slowed or will shrink.

The study has two parts; patients may be enrolled in either the first or second part of the study. The purpose of the first part is to determine the highest tolerable dose of RGX-202-01 alone and in combination with FOLFIRI. The second part will evaluate whether RGX-202-01 alone or RGX-202-01 combined with FOLFIRI might be effective treatment options for individuals with advanced cancers, using the highest tolerable dose of RGX-202-01 determined in the first part. Researchers also aim to understand the safety and side effects of RGX-202-01, as well as how the drug moves through the body (pharmacokinetics) and affects various types of cells in the blood and cancer (pharmacodynamics).

Eligibility

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

Inclusion Criteria:

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
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.

Exclusion Criteria:

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
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 UGT1A1*28, UGT1A1*6, 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

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Where can I participate?

Cedars-Sinai Cancer at SOCC

More about this Clinical Trial

What is the full name of this clinical trial?

RGX-202-001: A Phase 1 Study of RGX-202-01, a Small Molecule Inhibitor of the Creatine Transporter, SLC6a8, with or without FOLFIRI in Patients with Advanced Gastrointestinal Malignancies with Select Expansion Cohorts

Study Details

Disease Type/Condition

Anus, Colon, Esophagus, Other Digestive Organ, Pancreas, Prostate, Rectum, Small Intestine, Stomach

Principal Investigator

Hendifar, Andrew

Co-Investigators

Alain Mita, Jun Gong, Kamya Sankar, Kevin Scher

Age Group

Adult

Phase

IRB Number

Pro00055176

ClinicalTrials.gov ID

NCT03597581

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

clinicaltrials@cshs.org