Status:
TERMINATED
Trial of Ulixertinib in Combination With Hydroxychloroquine in Patients With Advanced Gastrointestinal (GI) Malignancies
Lead Sponsor:
BioMed Valley Discoveries, Inc
Conditions:
Tumor, Solid
Gastrointestinal Cancer
Eligibility:
All Genders
18+ years
Phase:
PHASE2
Brief Summary
This is an open-label, prospective phase two basket trial assessing the efficacy of ulixertinib in combination with hydroxychloroquine in patients with advanced gastrointestinal malignancies. All pati...
Detailed Description
This is an open-label, multicenter, phase II basket study of ulixertinib in combination with hydroxychloroquine in patients with advanced gastrointestinal malignancies harboring rat sarcoma virus (RAS...
Eligibility Criteria
Inclusion
- Male or female patient aged ≥ 18 years.
- Histologically confirmed esophageal adenocarcinoma, esophageal squamous cell carcinoma, GEJ adenocarcinoma, gastric adenocarcinoma, pancreatic adenocarcinoma, intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma, extrahepatic cholangiocarcinoma, or colorectal adenocarcinoma harboring a MAPK-mutated GI malignancy: KRAS, NRAS, HRAS, BRAF non-V600, MEK 1/2 (MAP2K1/2), or ERK 1/2 (MAPK3/1).
- Progression on or during standard lines of therapy:
- Patients with intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma, or extrahepatic cholangiocarcinoma must have progressed during or after receiving a first-line regimen of gemcitabine/cisplatin unless deemed ineligible by the treating investigator to receive chemotherapy-based regimens due to prior comorbidities.
- Patients with pancreatic adenocarcinoma must have progressed during or after first-line therapy of FOLFIRINOX/ mFOLFIRINOX, gemcitabine/nab-paclitaxel unless deemed ineligible by the treating investigator to receive chemotherapy-based regimens due to prior comorbidities.
- Patients with colorectal adenocarcinoma must have progressed during or after their first two lines of therapy, including FOLFOX ± Avastin and FOLFIRI ± Avastin, unless deemed ineligible by the treating investigator to receive chemotherapy-based regimens due to prior comorbidities.
- Patients with esophageal adenocarcinoma, esophageal squamous cell carcinoma, GEJ adenocarcinoma, or gastric adenocarcinoma must have progressed during or after their first two lines of therapy.
- Acceptable first-line regimens: FOLFOX, 5-FU/Cisplatin, FOLFIRI, Paclitaxel/Cisplatin or Carboplatin, Docetaxel/Cisplatin, DCF (or modifications thereof), or ECF (or modifications thereof) unless deemed ineligible by the treating investigator to receive chemotherapy-based regimens due to prior comorbidities.
- Acceptable second-line regimens: Ramucirumab/Paclitaxel, Docetaxel, Paclitaxel, Irinotecan, Trifluridine/Tipiracil, or FOLFIRI, unless deemed ineligible by the treating investigator to receive chemotherapy-based regimens due to prior comorbidities.
- Patients with deficient MisMatch Repair/High levels of MicroSatellite Instability (dMMR/MSI-H) tumors must have progressed during or after pembrolizumab.
- Measurable disease by RECIST 1.1 criteria by computed tomography (CT) or magnetic resonance imaging (MRI).
- Willing to provide a biopsy at the time points indicated on the Schedule of Activities.
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1.
- Adequate organ function as defined as:
- Hematologic:
- Absolute neutrophil count (ANC) ≥ 1500/mm3
- Platelet count ≥ 100,000/mm3
- Hemoglobin ≥ 9 g/dL
- Hepatic:
- Total Bilirubin ≤ 1.5x institutional upper limit of normal (ULN)
- Asparate animotransferace /Alanine aminotransferase (AST(SGOT)/ALT(SGPT)) ≤ 3 × institutional ULN
- Patients with liver metastases will be allowed to enroll with AST and ALT levels ≤ 5 x ULN.
- Renal:
- Estimated creatinine clearance ≥ 50 mL/min by Cockcroft-Gault formula:
- Males:
- (140-age) × weight \[kg\] / serum creatinine \[mgdL\] × 72
- Females:
- ((140-age) × weight \[kg\] / serum creatinine \[mgdL\] × 72)×0.85
- For female patients: Negative serum pregnancy test within 72 hours prior to first dose of study drugs for women of childbearing potential. The following definitions apply:
- Women of childbearing potential, defined as a sexually mature woman:
- Has not been naturally post-menopausal for at least 12 consecutive months (i.e., who has had menses anytime in the preceding 12 consecutive months).
- Has not undergone menopause, surgical sterilization (bilateral oophorectomy or hysterectomy).
- Underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
- Women not of childbearing potential:
- Amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, if any.
- Underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
- Male and female patients of childbearing potential agree to use highly effective contraception throughout the study and at least 90 days after the last study treatment administration.
- Recovery to baseline or ≤ Grade 1 CTCAE v5.0 from toxicities related to any prior cancer therapy, unless considered clinically not significant by the treating investigator.
- Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.
Exclusion
- Received systemic antineoplastic therapy (including unconjugated therapeutic antibodies and toxin immunoconjugates) or any investigational therapy ≤ 14 days or within five half-lives prior to starting study treatment, whichever is shorter.
- Received radiotherapy ≤ 14 days prior to the first dose of study treatment.
- Note: Localized radiation therapy for the treatment of symptomatic bone metastasis is allowed during that timeframe.
- Undergone major surgery ≤ 3 weeks prior to starting study drug or who have not fully recovered from major surgery.
- The diagnosis of another malignancy within ≤ 3 years before study enrollment, except for those considered to be adequately treated with no evidence of disease or symptoms and/or will not require therapy during the study duration (i.e., basal cell or squamous cell skin cancer, carcinoma in situ of the breast, bladder or of the cervix, or low-grade prostate cancer with Gleason Score ≤ 6).
- Known uncontrolled brain metastases or cranial epidural disease.
- Note: Patients with stable brain metastases either treated or being treated with a stable dose of steroids (\<20 mg of prednisone daily or equivalent) or anticonvulsants, with no dose change within 4 weeks before the first study drug dose, and no anticipated dose change, are eligible. In the event of steroid taper post-radiation therapy, taper must be complete within 2 weeks before Baseline.
- History or current evidence of central serous retinopathy (CSR) or retinal vein occlusion (RVO) or current risk factors for RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity).
- Current evidence of uncontrolled, significant intercurrent illness including, but not limited to, the following conditions:
- Cardiovascular disorders:
- Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias.
- Stroke (including transient ischemic attack \[TIA\]), myocardial infarction (MI), or other ischemic events, or thromboembolic event (eg, deep venous thrombosis, pulmonary embolism) within 3 months before the first dose.
- Duration of QT interval (QTc prolongation) defined as a QTcF \> 500 ms.
- Known congenital long QT.
- Left ventricular ejection fraction \< 50%.
- History of seizures
- Impairment of gastrointestinal function or gastrointestinal disease (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome).
- Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures (e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, \[patients may not receive the drug through a feeding tube\], social/ psychological issues, etc.)
- Prior stomach or duodenal resection that in the opinion of the Principal Investigator and Medical Monitor would affect the breakdown and absorption of the study medications. A patient with a feeding tube should also be excluded, as ulixertinib capsules cannot be broken apart.
- Known HIV infection with a detectable viral load within 6 months of the anticipated start of treatment.
- Note: Patients on effective antiretroviral therapy with an undetectable viral load within 6 months of the anticipated start of treatment are eligible for this trial.
- Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination, radiographic findings, and tuberculosis (TB) testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), or hepatitis C.
- Note: Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
- Medical, psychiatric, cognitive or other conditions that may compromise the patient's ability to understand the patient information, give informed consent, comply with the study protocol or complete the study.
- Known prior severe hypersensitivity to investigational product (IP) or any component in its formulations (NCI CTCAE v5.0 Grade ≥ 3).
- Patients taking prohibited medications as described in protocol. A washout period of prohibited medications for a period of at least 5 half-lives or as clinically indicated should occur before the start of treatment.
Key Trial Info
Start Date :
May 26 2022
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
July 14 2024
Estimated Enrollment :
47 Patients enrolled
Trial Details
Trial ID
NCT05221320
Start Date
May 26 2022
End Date
July 14 2024
Last Update
September 25 2025
Active Locations (9)
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1
University of Arizona Cancer Center
Tucson, Arizona, United States, 85719
2
University of California San Francisco
San Francisco, California, United States, 94143
3
University of Kansas Cancer Center
Fairway, Kansas, United States, 66205
4
Rogel Cancer Center, University of Michigan Health
Ann Arbor, Michigan, United States, 48109