Trial Title:
CPI-613 (Devimistat) in Combination With Hydroxychloroquine and 5-fluorouracil or Gemcitabine in Treating Patients With Advanced Chemorefractory Solid Tumors
NCT ID:
NCT05733000
Condition:
Advanced Biliary Tract Carcinoma
Advanced Colorectal Carcinoma
Advanced Gastroesophageal Junction Adenocarcinoma
Advanced Lung Adenocarcinoma
Advanced Malignant Solid Neoplasm
Advanced Ovarian Carcinoma
Advanced Pancreatic Carcinoma
Advanced Urothelial Carcinoma
Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8
Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8
Metastatic Biliary Tract Carcinoma
Metastatic Colorectal Carcinoma
Metastatic Gastroesophageal Junction Adenocarcinoma
Metastatic Lung Adenocarcinoma
Metastatic Ovarian Carcinoma
Metastatic Pancreatic Carcinoma
Metastatic Urothelial Carcinoma
Refractory Biliary Tract Carcinoma
Refractory Colorectal Carcinoma
Refractory Gastroesophageal Junction Adenocarcinoma
Refractory Lung Adenocarcinoma
Refractory Ovarian Carcinoma
Refractory Pancreatic Carcinoma
Refractory Urothelial Carcinoma
Stage II Pancreatic Cancer AJCC v8
Stage III Colorectal Cancer AJCC v8
Stage III Lung Cancer AJCC v8
Stage III Ovarian Cancer AJCC v8
Stage III Pancreatic Cancer AJCC v8
Stage IV Colorectal Cancer AJCC v8
Stage IV Lung Cancer AJCC v8
Stage IV Ovarian Cancer AJCC v8
Stage IV Pancreatic Cancer AJCC v8
Conditions: Official terms:
Carcinoma
Lung Neoplasms
Colorectal Neoplasms
Adenocarcinoma
Pancreatic Neoplasms
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Carcinoma, Transitional Cell
Esophageal Neoplasms
Adenocarcinoma of Lung
Thioctic Acid
Hydroxychloroquine
Gemcitabine
Fluorouracil
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
COHORT 1 (Devimistat, 5-FU, HCQ)
Arm group label:
COHORT 2 (Devimistat, 5-FU, HCQ)
Arm group label:
COHORT 3 (Devimistat, 5-FU, HCQ, Gemcitabine)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT
Arm group label:
COHORT 1 (Devimistat, 5-FU, HCQ)
Arm group label:
COHORT 2 (Devimistat, 5-FU, HCQ)
Arm group label:
COHORT 3 (Devimistat, 5-FU, HCQ, Gemcitabine)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized Tomography
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Drug
Intervention name:
Devimistat
Description:
Receive IV
Arm group label:
COHORT 1 (Devimistat, 5-FU, HCQ)
Arm group label:
COHORT 2 (Devimistat, 5-FU, HCQ)
Arm group label:
COHORT 3 (Devimistat, 5-FU, HCQ, Gemcitabine)
Other name:
Alpha-Lipoic Acid Analogue CPI-613
Other name:
CPI 613
Other name:
CPI-613
Intervention type:
Drug
Intervention name:
Fluorouracil
Description:
Receive IV
Arm group label:
COHORT 1 (Devimistat, 5-FU, HCQ)
Arm group label:
COHORT 2 (Devimistat, 5-FU, HCQ)
Arm group label:
COHORT 3 (Devimistat, 5-FU, HCQ, Gemcitabine)
Other name:
5 Fluorouracil
Other name:
5 Fluorouracilum
Other name:
5 FU
Other name:
5-Fluoro-2,4(1H, 3H)-pyrimidinedione
Other name:
5-Fluorouracil
Other name:
5-Fluracil
Other name:
5-Fu
Other name:
5FU
Other name:
AccuSite
Other name:
Carac
Other name:
Fluoro Uracil
Other name:
Fluouracil
Other name:
Flurablastin
Other name:
Fluracedyl
Other name:
Fluracil
Other name:
Fluril
Other name:
Fluroblastin
Other name:
Ribofluor
Other name:
Ro 2-9757
Other name:
Ro-2-9757
Intervention type:
Drug
Intervention name:
Gemcitabine Hydrochloride
Description:
Receive IV
Arm group label:
COHORT 3 (Devimistat, 5-FU, HCQ, Gemcitabine)
Other name:
dFdCyd
Other name:
Difluorodeoxycytidine Hydrochloride
Other name:
FF 10832
Other name:
FF-10832
Other name:
FF10832
Other name:
Gemcitabine HCI
Other name:
Gemzar
Other name:
LY-188011
Other name:
LY188011
Intervention type:
Drug
Intervention name:
Hydroxychloroquine
Description:
Receive PO
Arm group label:
COHORT 1 (Devimistat, 5-FU, HCQ)
Arm group label:
COHORT 2 (Devimistat, 5-FU, HCQ)
Arm group label:
COHORT 3 (Devimistat, 5-FU, HCQ, Gemcitabine)
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
COHORT 1 (Devimistat, 5-FU, HCQ)
Arm group label:
COHORT 2 (Devimistat, 5-FU, HCQ)
Arm group label:
COHORT 3 (Devimistat, 5-FU, HCQ, Gemcitabine)
Other name:
Magnetic Resonance
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
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.
Detailed description:
PRIMARY OBJECTIVE:
I. The primary objective of this study will be to estimate the overall response rate
(ORR) of treatment with devimistat (CPI-613) plus HCQ and, depending on the cohort and
indication, either 5-FU or gemcitabine.
SECONDARY OBJECTIVES:
I. Evaluate progression-free survival (PFS) of patients with solid tumors that are
treated with CPI-613 plus HCQ and, depending on the cohort and indication, either 5-FU or
gemcitabine.
II. Determine overall survival (OS) of patients with solid tumors that are treated with
CPI-613 plus HCQ and, depending on the cohort and indication, either 5-FU or gemcitabine.
III. Assess duration of response (DOR) of patients with solid tumors that are treated
with CPI-613 plus HCQ and, depending on the cohort and indication, either 5-FU or
gemcitabine.
IV. Assess safety and tolerability for patients with solid tumors treated with specified
treatments.
EXPLORATORY OBJECTIVES:
I. Blood from patients in cohort 3 that consent will be collected at baseline, cycle 1,
day 1 (C1D1), C1D15, C2D1, and at the time of treatment discontinuation for further
molecular and metabolic analysis, possibly including but not limited to proteomic,
metabolomic, and genetic/genomic analysis.
OUTLINE: Patients are assigned to 1 of 3 cohorts.
COHORT 1: Patients with colorectal cancer receive devimistat intravenously (IV), 5-FU IV,
plus HCQ orally (PO) on study. Patients also undergo computed tomography (CT) and/or
magnetic resonance imaging (MRI) and undergo blood specimen collection throughout the
study.
COHORT 2: 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.
COHORT 3: 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.
Criteria for eligibility:
Criteria:
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).
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Northwestern University
Address:
City:
Chicago
Zip:
60611
Country:
United States
Status:
Recruiting
Contact:
Last name:
Devalingam Mahalingam, MD, PhD
Phone:
312-695-6929
Email:
mahalingam@nm.org
Investigator:
Last name:
Devalingam Mahalingam, MD, PhD
Email:
Principal Investigator
Start date:
March 8, 2023
Completion date:
March 4, 2030
Lead sponsor:
Agency:
Northwestern University
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
Northwestern University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05733000
