Recruiting

Phase 2

CPI-613, Hydroxychloroquine, 5-Fluorouracil, GemcitabineCPI-613 (Devimistat) in Combination With Hydroxychloroquine and 5-fluorouracil or Gemcitabine in Treating Patients With Advanced Chemorefractory Solid Tumors

Sponsor:

Northwestern University

Code:

NCT05733000

Conditions

Advanced Biliary Tract Carcinoma

Advanced Colorectal Carcinoma

Advanced Gastroesophageal Junction Adenocarcinoma

Advanced Lung Adenocarcinoma

Advanced Malignant Solid Neoplasm

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biospecimen Collection

Computed Tomography

Devimistat

Fluorouracil

Gemcitabine Hydrochloride

Study Details

Brief summary:

This phase II trial tests how well CPI-613 (devimistat) in combination with hydroxychloroquine (HCQ) and 5-fluorouracil (5-FU) or gemcitabine works in patients with solid tumors that may have spread from where they first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that have not responded to chemotherapy medications (chemorefractory). Metabolism is how the cells in the body use molecules (carbohydrates, fats, and proteins) from food to get the energy they need to grow, reproduce and stay healthy. Tumor cells, however, do this process differently as they use more molecules (glucose, a type of carbohydrate) to make the energy they need to grow and spread. CPI-613 works by blocking the creation of the energy that tumor cells need to survive, grow in the body and make more tumor cells. When the energy production they need is blocked, the tumor cells can no longer survive. Hydroxychloroquine is a drug used to treat malaria and rheumatoid arthritis and may also improve the immune system in a way that tumors may be better controlled. Fluorouracil is in a class of medications called antimetabolites. It works by killing fast-growing abnormal cells. Gemcitabine is a chemotherapy drug that blocks the cells from making DNA and may kill tumor cells. CPI-613 (devimistat) in combination with hydroxychloroquine and 5-fluorouracil or gemcitabine may work to better treat advanced solid tumors.

Conditions

Advanced Biliary Tract Carcinoma

Advanced Colorectal Carcinoma

Advanced Gastroesophageal Junction Adenocarcinoma

Advanced Lung Adenocarcinoma

Advanced Malignant Solid Neoplasm

Study ID

NCT05733000

Start date

Mar 8, 2023

Status verified date

Feb, 2023

Completion date

Mar 4, 2030

Anticipated

Primary completion date

Jan 4, 2028

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

Patients must have histologically confirmed cancer for which standard-of-care curative measures are no longer effective or be intolerant to those agents. Patients in cohort 1 must have colorectal cancer. Patients in cohort 2 must have pancreatic cancer. Patients in cohort 3 may have any of the following cancers:

Biliary
Gastroesophageal
Urothelial
Ovarian
Non-small cell lung (adenocarcinoma only)
Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 disease.
Patients must have radiographic documentation of metastatic disease with imaging within =< 6 weeks prior to registration.
Patients must be age >= 18 years.
Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Performance Status of 2 will be allowed with approval from principle investigator (PI) on a case-by case basis.

Note: Performance status of 2 will be allowed with approval from PI on a case-by case basis. Documentation of PI approval in these cases will be stored with inclusion/exclusion signed checklist for patient and/or in patient's shadow chart.
Patients must have exhausted all available molecularly targeted therapies (e.g., anti-PD-1/anti-PD-L1 agents where indicated).
Absolute neutrophil count (ANC) >= 1,500/mcL (within the last 14 days of screening)
Hemoglobin (Hgb) >= 9 g/dL (within the last 14 days of screening) (Transfusions permitted. Eligibility labs should be drawn >= 7 days from transfusion).
Platelets (PLT) >= 100,000/mcL (within the last 14 days of screening) (Transfusions permitted. Eligibility labs should be drawn >= 7 days from transfusion).
INR (international normalized ratio) =< 1.6 (within the last 14 days of screening) (unless receiving anticoagulation therapy) If receiving anticoagulant: INR =< 3.0 and no active bleeding, (i.e., no bleeding within 14 days prior to first dose of study therapy).
Total bilirubin =<1.5 x Institutional upper limit of normal (ULN) (within the last 14 days of screening)

Note: Patients with Gilbert's Syndrome are exempt. Patients with liver metastases with no significant bilirubin obstruction may have a total bilirubin level of =< 2.0 mg/dL.
Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT) =< 2.5 x institutional ULN (within the last 14 days of screening)

Note: If liver metastases are present, then =< 5 x ULN is allowed.
Alanine transaminase (ALT) serum glutamic-pyruvic transaminase (SGPT) =< 2.5 x institutional ULN (within the last 14 days of screening)

Note: If liver metastases are present, then =< 5 x ULN is allowed.
Serum albumin > 3.0 g/dL (within the last 14 days of screening)
Creatinine =< 1.5 x ULN OR glomerular filtration rate (GFR) >= 50 mL/min/1.73 m\^2 (within the last 14 days of screening)

eGFR is estimated GFR calculated by the abbreviated Modification of Diet in Renal Disease (MDRD) equation
The effects of combination treatment of CPI-613, 5-FU, gemcitabine, and HCQ on the developing human fetus are unknown. For this reason and because antineoplastic agents as well as other therapeutic agents used in this trial are known to be teratogenic, patients of child-bearing potential (POCBP) regardless of gender must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) from time of informed consent, for the duration of study participation, and for 180 days following completion of therapy. Patients who can impregnate their partners regardless of gender must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) from time of informed consent, for the duration of study participation, and for 180 days following completion of therapy. Should a patient become pregnant or suspect they are pregnant while they or their partner is participating in this study, they should inform their treating physician immediately.

Note: At the discretion of the investigator, acceptable methods of contraception may include total abstinence in cases where the lifestyle of the patient ensures compliance. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, postovulation methods\] and withdrawal are not acceptable methods of contraception.)
Note: A POCBP is any person with an egg-producing reproductive tract (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

Has not undergone a hysterectomy or bilateral oophorectomy
Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for > 12 months)
POCBP must have a negative pregnancy test prior to registration on study.

Note: If negative pregnancy test result is >7 days from first dose of study treatment it must be repeated at time of first dose of study treatment (with any of the four drugs used in this study).
For patients with a known history of human immunodeficiency virus (HIV), infected patients on effective anti-retroviral therapy must have a viral load undetectable for 6 months prior to registration.
For patients with a known history of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
Patients with a known history of hepatitis C virus (HCV) infection must have been treated and cured. Patients with HCV infection who are currently on treatment, must have an undetectable HCV viral load. Patients with known history or current symptoms of cardiac disease, or history of treatment with cardio toxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. Patients must be class 2B or better.

Note: Patients with pacemakers where corrected QT interval (QTc) is not a reliable measure will require an evaluation by a cardiologist to exclude co-existing cardiac conditions which would prohibit safe participation in the study.
Patients must have the ability to understand and the willingness to sign a written informed consent document for the duration of the entirety of the study.
Patients must be reliable, willing to make themselves available for the duration of the entire study and willing to follow screening procedures.

Exclusion Criteria:

Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1).

Note: Patients who experience adverse events of alopecia and peripheral neuropathy that have not recovered are eligible; patients with any lab abnormality that is above grade 1 related to previous therapy found to be not clinically significant will also be eligible.
Patients with symptomatic brain metastases currently using corticosteroids.

Note: Patients with brain metastases who are asymptomatic and off corticosteroids for at least one week are eligible.
Patients with severe obstructive pulmonary disease or interstitial lung disease.
Patients with a history of myocardial infarction that is <90 days prior to registration.
Patients using concomitant medications that prolong the QT/QTc intervals. For example, patients receiving amiodarone. Using amiodarone together with hydroxychloroquine can increase the risk of long QT syndrome that although rare, may be serious, and potentially life-threatening.
Patients with a history of additional risk factors for drug-induced QT prolongation or Torsades de Pointes (TdP) (e.g., heart failure, hypokalemia, family history of long QT syndrome).
Patients with major surgery or significant traumatic injury =< 21 days prior to registration.
Patients receiving treatment with low dose chemotherapy concurrent with radiation =< 21 days prior to registration.

OR patients who have had chemotherapy or radiotherapy =< 21 days (42 days for nitrosoureas or mitomycin C) prior to registration.

Note: Palliative radiation before and during study participation is permissible providing it is not to a target lesion.

Patients who have an uncontrolled intercurrent illness including, but not limited to any of the following, are not eligible:
Ongoing or active infection requiring systemic treatment.
Clinically significant complications such as perforation, gastrointestinal bleeding, or diverticulitis within 42 days prior to registration.
Symptomatic congestive heart failure; symptomatic coronary artery disease, symptomatic angina pectoris, or symptomatic myocardial infarction.
Unstable angina pectoris.
Unstable cardiac arrhythmia.
Psychiatric illness/social situations that would limit compliance with study requirements.
Active substance abuse.
Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints.

Patients who are pregnant or nursing.
Patients with Fridericia-corrected QT interval (QTcF) > 470 msec (female) or > 450 (male), or history of congenital long QT syndrome. Any electrocardiogram (ECG) abnormality that in the opinion of the investigator would preclude safe participation in the study.
Patients who have pre-existing retinopathy of the eye.
Patients who are unable to swallow or retain and absorb oral medication
Patients with known hypersensitivity to any of the following: CPI or its inactive components, 4-aminoquinoline compounds, or quinine.
Patients with poorly controlled diabetes mellitus (glycosylated hemoglobin (HbA1c) of > 7%, pre-prandial capillary plasma glucose > 130mg/dl, and peak postprandial capillary plasma glucose of > 180mg/dl).

Study Design

Enrollment

94 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: COHORT 1 (Devimistat, 5-FU, HCQ)

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.

experimental: COHORT 2 (Devimistat, 5-FU, HCQ)

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.

experimental: COHORT 3 (Devimistat, 5-FU, HCQ, Gemcitabine)

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.

Interventions

Biospecimen Collection

Undergo blood sample collection

Computed Tomography

Undergo CT

Devimistat

Receive IV

Fluorouracil

Receive IV

Gemcitabine Hydrochloride

Receive IV

Hydroxychloroquine

Receive PO

Magnetic Resonance Imaging

Undergo MRI

Primary outcome measure

Overall response rate (ORR) [ Time Frame: Time from baseline to disease progression, initiates subsequent anti-cancer therapy, or 24 months (whichever occurs first) ]

Central Contacts and Locations

Central contacts

Study Coordinator

3126953101 cancer@northwestern.edu

Locations

Northwestern University

Recruiting

Chicago, Illinois, United States, 60611

Contacts

Devalingam Mahalingam, MD, PhD

312-695-6929 mahalingam@nm.org

Principal Investigator:

Devalingam Mahalingam, MD, PhD

More Information

Sponsor

Northwestern University

Last update posted

Mar 10, 2023

Last verified

Feb, 2023

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Northwestern University on 2023-03-10.