CPI-613 (Devimistat) in Combination With Hydroxychloroquine and 5-fluorouracil or Gemcitabine in Treating Patients With Advanced Chemorefractory Solid Tumors
Phase II Open-Label Multi-Cohort Study Evaluating CPI-613 (Devimistat) in Combination With Hydroxychloroquine and 5-fluorouracil or Gemcitabine in Patients With Advanced Chemorefractory Colorectal, Pancreatic, or Other Solid Cancers
4 other identifiers
interventional
94
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Mar 2023
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 24, 2023
CompletedFirst Posted
Study publicly available on registry
February 17, 2023
CompletedStudy Start
First participant enrolled
March 8, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 4, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 4, 2030
March 10, 2023
February 1, 2023
4.8 years
January 24, 2023
March 8, 2023
Conditions
Outcome Measures
Primary Outcomes (1)
Overall response rate (ORR)
Will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 in patients with solid tumors treated under this protocol. ORR is defined as the percentage of patients with documented complete response (CR) plus the percentage of patients with documented partial response (PR). ORR will be reported with the corresponding exact confidence intervals.
Time from baseline to disease progression, initiates subsequent anti-cancer therapy, or 24 months (whichever occurs first)
Secondary Outcomes (4)
Progression free survival (PFS)
Time that elapses between the day of subject registration and the earlier of the day of first documented disease progression by clinical or radiographic evaluation or death from any cause, assessed up to 24 months
Overall survival (OS)
Time that elapses between the day of subject registration and death from any cause, assessed up to 24 months
Duration of response (DOR)
Time elapsed from the day when CR or PR is first observed until the earlier of the day of first documented disease progression or death, assessed up to 24 months
Incidence of adverse events
Up to 30 days post treatment
Study Arms (3)
COHORT 1 (Devimistat, 5-FU, HCQ)
EXPERIMENTALPatients 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.
COHORT 2 (Devimistat, 5-FU, HCQ)
EXPERIMENTALPatients 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.
COHORT 3 (Devimistat, 5-FU, HCQ, Gemcitabine)
EXPERIMENTALPatients 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
Undergo blood sample collection
Undergo CT
Receive IV
Receive IV
Receive IV
Receive PO
Undergo MRI
Eligibility Criteria
You may qualify if:
- 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.
- 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).
- +22 more criteria
You may not qualify if:
- 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.
- +12 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Northwestern Universitylead
- National Cancer Institute (NCI)collaborator
Study Sites (1)
Northwestern University
Chicago, Illinois, 60611, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Devalingam Mahalingam
Northwestern University
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 24, 2023
First Posted
February 17, 2023
Study Start
March 8, 2023
Primary Completion (Estimated)
January 4, 2028
Study Completion (Estimated)
March 4, 2030
Last Updated
March 10, 2023
Record last verified: 2023-02