What side effects are associated with this type of intervention?

Common treatments for gastrointestinal cancer, particularly those involving MAPK pathway inhibitors like Ulixertinib and autophagy inhibitors like Hydroxychloroquine, often result in side effects such as diarrhea, fatigue, skin rash, liver enzyme abnormalities, gastrointestinal disturbances (nausea, vomiting), retinal toxicity, and muscle weakness. These side effects reflect the typical adverse reactions associated with targeted therapies and autophagy inhibitors.

What prior FDA approvals exist?

FDA-approved treatments for gastrointestinal cancers include various targeted therapies and immunotherapies. For instance, Pembrolizumab, an anti-PD-1 monoclonal antibody, has been approved for use in esophageal cancer with high PD-L1 expression. Bevacizumab, an anti-VEGF antibody, has shown activity in combination with chemotherapy for gastrointestinal neuroendocrine tumors. While specific approvals for MAPK pathway inhibitors and autophagy inhibitors in gastrointestinal cancers are not detailed, these examples illustrate the range of targeted and immunotherapeutic options available.

What other types of research exist?

Promising alternatives for gastrointestinal cancer treatment include: <ol> <li>Regorafenib: A multikinase inhibitor that has shown significant improvement in progression-free survival in patients with advanced gastrointestinal stromal tumors following failure of imatinib and sunitinib.</li> <li></li> </ol> Pembrolizumab: An immune checkpoint inhibitor that has maintained health-related quality of life in patients with PD-L1-positive advanced gastric/gastroesophageal junction adenocarcinoma. 3. Pilaralisib: A PI3K pathway inhibitor that has been evaluated in combination with paclitaxel and carboplatin, showing potential in patients with advanced solid tumors.

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Autophagy Inhibitor

Ulixertinib + Hydroxychloroquine for Gastrointestinal Cancer

Phase 2

Waitlist Available

Research Sponsored by BioMed Valley Discoveries, Inc

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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)

Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1

Must not have

Current evidence of uncontrolled, significant intercurrent illness including cardiovascular disorders, history of seizures, impairment of gastrointestinal function or gastrointestinal disease, and any other condition that would contraindicate the patient's participation in the clinical study

Patients taking prohibited medications as described in protocol

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline until safety follow-up visit (up to 30 months)

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a combination of two drugs, ulixertinib and hydroxychloroquine, in patients with advanced gastrointestinal cancers who have specific genetic mutations. The drugs aim to stop cancer growth and make the cancer cells weaker. Ulixertinib is designed to inhibit certain proteins involved in cancer cell growth.

Who is the study for?

Adults with advanced gastrointestinal cancers harboring MAPK mutations, who have progressed after standard treatments. Eligible participants include those with specific types of esophageal, gastric, pancreatic, or colorectal cancer. They must not be pregnant, agree to use effective contraception and have adequate organ function. Excluded are individuals with recent antineoplastic therapy or surgery, other malignancies within 3 years (except adequately treated), uncontrolled illnesses or infections like hepatitis B/C.

What is being tested?

The trial is testing the combination of Ulixertinib and Hydroxychloroquine in patients with certain gastrointestinal cancers that carry a MAPK mutation. It's an open-label phase two study where responses from an initial group determine if a second stage proceeds.

What are the potential side effects?

Potential side effects may include vision problems like retinal issues, increased risk of infection due to immune system impact, digestive disturbances given the GI focus of treatment, and general reactions such as fatigue or skin sensitivity.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My cancer is one of the listed types and has a specific mutation.

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I can carry out all my self-care but might not be able to do heavy physical work.

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My condition worsened despite treatment.

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My cancer can be measured on scans.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I do not have any severe illnesses that would stop me from joining the study.

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I am not taking any medications that are not allowed in the study.

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I have or had eye conditions like CSR or RVO, or I'm at risk for RVO.

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I do not have an active infection like TB, hepatitis B, or C.

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I had major surgery less than 3 weeks ago or haven't fully recovered from one.

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I've had surgery on my stomach or upper intestine that affects how I absorb medication.

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I have untreated brain metastases or cranial epidural disease.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline until safety follow-up visit (up to 30 months)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline until safety follow-up visit (up to 30 months)

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline until safety follow-up visit (up to 30 months) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Overall response rate as defined by the proportion of patients achieving a confirmed partial response (PR) and complete response (CR) (defined by response evaluation criteria in solid tumors (RECIST 1.1) as evaluated by the local treating investigator.

The incidence and frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by type, severity (as defined by the NCI CTCAE, version 5.0), seriousness, duration, and relationship to study treatment.

Secondary study objectives

Progression-free survival (PFS) as defined as the time from study drug initiation to the time of documented disease progression (as assessed by RECIST 1.1) or death from any cause.

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Stage 2 - basket expansion based on Stage 1Experimental Treatment2 Interventions

Ulixertinib: 450mg BID, orally, days 1-28 Hydroxychloroquine: 600mg BID, orally, days 1-28 Cycles repeat every 28 days in absence of disease progression or unacceptable toxicity

Group II: Stage 1 - 5 baskets included, based on primary diseaseExperimental Treatment2 Interventions

Ulixertinib: 450mg twice daily (BID), orally, days 1-28 Hydroxychloroquine: 600mg BID, orally, days 1-28 Cycles repeat every 28 days in absence of disease progression or unacceptable toxicity

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Ulixertinib

2020

Completed Phase 1

~20

Hydroxychloroquine

2017

Completed Phase 4

~5350

0 / 11Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for gastrointestinal cancer often target specific molecular pathways involved in cancer cell growth and survival. Ulixertinib, a MAPK pathway inhibitor, works by blocking the mitogen-activated protein kinase (MAPK) pathway, which is frequently activated in cancer cells, leading to uncontrolled cell proliferation. Hydroxychloroquine, an autophagy inhibitor, disrupts the process of autophagy, a cellular mechanism that cancer cells use to survive under stress conditions such as nutrient deprivation. By inhibiting these pathways, these treatments aim to reduce tumor growth and enhance cancer cell death, offering a targeted approach that can be more effective and potentially less toxic than traditional chemotherapy. This is particularly important for gastrointestinal cancer patients, as these targeted therapies can provide new options for those with advanced or treatment-resistant forms of the disease.

Therapeutic approaches for relapsed/refractory adult acute lymphoblastic leukemia (ALL), a review on monoclonal antibodies and targeted therapies.Safety profile of new anticancer drugs.