What is the mechanism of action of this treatment?

Common treatments for Gastroesophageal Junction (GEJ) Adenocarcinoma, such as CPI-613 (devimistat), work by inhibiting metabolic pathways essential for tumor cell energy production, effectively starving the cancer cells. Other treatments like 5-fluorouracil (5-FU) and gemcitabine disrupt DNA synthesis, leading to cell death. Combining these with agents like hydroxychloroquine, which may enhance immune response, provides a comprehensive approach to combat the cancer. Understanding these mechanisms is crucial for GEJ Adenocarcinoma patients as it underscores the strategic targeting of cancer cell survival pathways to improve treatment efficacy and patient outcomes.

What side effects are associated with this type of intervention?

Common treatments for Gastroesophageal Junction Adenocarcinoma include chemotherapy agents such as 5-fluorouracil (5-FU) and gemcitabine, often combined with metabolic inhibitors like CPI-613 (devimistat). Known side effects of these treatments include gastrointestinal issues (nausea, vomiting, diarrhea), hematologic toxicities (neutropenia, anemia), fatigue, mucositis, and potential liver and kidney dysfunction. Metabolic inhibitors like CPI-613 may also cause specific side effects such as peripheral neuropathy and metabolic disturbances. Patients should discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

The FDA has approved several treatments for Gastroesophageal Junction Adenocarcinoma, including chemotherapeutic agents and targeted therapies. Notably, drugs like 5-fluorouracil (5-FU) and gemcitabine, which are used in combination with CPI-613 (devimistat) in clinical trials, have been approved for their ability to disrupt DNA synthesis and kill rapidly dividing tumor cells. Additionally, other metabolic pathway inhibitors, such as those targeting the epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF), have been approved for similar cancers, although specific approvals for metabolic inhibitors like CPI-613 are limited.

What other types of research exist?

TAK-264 (MLN0264) is a promising novel alternative for Gastroesophageal Junction Adenocarcinoma patients. It targets guanylyl cyclase C (GCC) and has shown antitumor activity in advanced gastrointestinal malignancies. Another potential option is the pan-erbB tyrosine kinase inhibitor CI-1033, which inhibits EGFR and HER2, showing significant antitumor effects in esophageal cancer models.

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Metabolic Inhibitor

Devimistat Combo for Advanced Cancers

Phase 2

Recruiting

Led By Devalingam Mahalingam

Research Sponsored by Northwestern University

Eligibility Criteria Checklist

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

Must have

Patients must meet specified renal function criteria

Patients must be age >= 18 years

Must not have

Patients who are unable to swallow or retain and absorb oral medication

Patients with poorly controlled diabetes mellitus

Timeline

Screening 3 weeks

Treatment Varies

Follow Up time from baseline to disease progression, initiates subsequent anti-cancer therapy, or 24 months (whichever occurs first)

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a combination of three drugs to treat patients with advanced solid tumors that have spread or are resistant to previous treatments. The drugs work together to block energy production in tumor cells, boost the immune system, and kill fast-growing tumor cells. The goal is to see how well this combination works and how safe it is for patients.

Who is the study for?

This trial is for adults with advanced solid tumors like colorectal, pancreatic, biliary, gastroesophageal, urothelial, ovarian or lung cancer (adenocarcinoma only) that haven't responded to standard treatments. Participants must have good physical function and meet specific blood count and organ function criteria. They should not be pregnant/nursing and must agree to use contraception if applicable.

What is being tested?

The trial tests CPI-613 (devimistat) combined with hydroxychloroquine and either 5-fluorouracil or gemcitabine against advanced chemorefractory solid tumors. Devimistat targets the energy production of tumor cells while hydroxychloroquine may enhance immune response; both fluorouracil and gemcitabine are chemotherapy drugs aiming to kill fast-growing abnormal cells.

What are the potential side effects?

Potential side effects include fatigue, nausea, diarrhea from chemotherapy drugs like fluorouracil and gemcitabine; devimistat might cause metabolic disturbances since it affects cell energy processes; hydroxychloroquine can lead to vision changes or muscle weakness.

Eligibility Criteria

Inclusion Criteria

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

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My kidney function meets the required levels.

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I am 18 years old or older.

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I have pancreatic cancer.

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I have tried all targeted therapy options available for my condition.

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My liver is functioning within normal ranges.

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I am fully active or restricted in physically strenuous activity but can do light work.

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My cancer cannot be cured with standard treatments, or I cannot tolerate them.

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I have colorectal cancer.

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I had hepatitis C but have been successfully treated and cured.

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I have chronic hepatitis B but it's under control with medication.

Exclusion Criteria

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

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I cannot swallow or properly absorb pills.

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My diabetes is not well-managed.

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I have a pre-existing eye condition affecting my retina.

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I am using corticosteroids for my brain metastases symptoms.

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I am taking medication that affects my heart's electrical cycle.

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I do not have any unmanaged ongoing illnesses.

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I have severe lung disease.

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I have certain heart conditions or ECG abnormalities.

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I started low dose chemotherapy with radiation less than 3 weeks ago.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ time from baseline to disease progression, initiates subsequent anti-cancer therapy, or 24 months (whichever occurs first)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~time from baseline to disease progression, initiates subsequent anti-cancer therapy, or 24 months (whichever occurs first)

This trial's timeline: 3 weeks for screening, Varies for treatment, and time from baseline to disease progression, initiates subsequent anti-cancer therapy, or 24 months (whichever occurs first) 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 (ORR)

Secondary study objectives

Duration of response (DOR)

Incidence of adverse events

Overall survival (OS)

+1 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

3Treatment groups

Experimental Treatment

Group I: COHORT 3 (Devimistat, 5-FU, HCQ, Gemcitabine)Experimental Treatment7 Interventions

Patients with gastroesophageal cancer receive devimistat IV, 5-FU IV, plus HCQ PO on study. Patients with urothelial, ovarian, or non-small cell lung cancer receive devimistat IV, gemcitabine IV, plus HCQ PO on study. Patients with biliary tumors receive devimistat IV and gemcitabine IV or HCQ PO on study. Patients also undergo CT and/or MRI and undergo blood specimen collection throughout the study.

Group II: COHORT 2 (Devimistat, 5-FU, HCQ)Experimental Treatment6 Interventions

Patients with pancreatic cancer receive devimistat IV, 5-FU IV, plus HCQ PO on study. Patients also undergo CT and/or MRI and undergo blood specimen collection throughout the study.

Group III: COHORT 1 (Devimistat, 5-FU, HCQ)Experimental Treatment6 Interventions

Patients with colorectal cancer receive devimistat IV, 5-FU IV, plus HCQ PO on study. Patients also undergo CT and/or MRI and undergo blood specimen collection throughout the study.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Biospecimen Collection

2004

Completed Phase 3

~2020

Computed Tomography

2017

Completed Phase 2

~2740

Fluorouracil

2014

Completed Phase 3

~11700

Gemcitabine Hydrochloride

2005

Completed Phase 3

~5420

Hydroxychloroquine

2017

Completed Phase 4

~5360

Magnetic Resonance Imaging

2017

Completed Phase 3

~1160

0 / 19Eligibility 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

Common treatments for Gastroesophageal Junction (GEJ) Adenocarcinoma, such as CPI-613 (devimistat), work by inhibiting metabolic pathways essential for tumor cell energy production, effectively starving the cancer cells. Other treatments like 5-fluorouracil (5-FU) and gemcitabine disrupt DNA synthesis, leading to cell death. Combining these with agents like hydroxychloroquine, which may enhance immune response, provides a comprehensive approach to combat the cancer. Understanding these mechanisms is crucial for GEJ Adenocarcinoma patients as it underscores the strategic targeting of cancer cell survival pathways to improve treatment efficacy and patient outcomes.