Neoplasms

All Conditions

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Protective Agents

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Vitamin B Complex

Trace Elements

Alpha-lipoic Acid

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Vitamin B9

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.

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.

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.

Biospecimen Collection

Computed Tomography

Devimistat

Gemcitabine Hydrochloride

Magnetic Resonance Imaging

Study Coordinator

Devalingam Mahalingam, MD, PhD

Devalingam Mahalingam

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.

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.

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

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.

Will be assessed using Kaplan-Meier estimates. PFS for the main cohorts (cohort 1 and cohort 2) and exploratory cohort (cohort 3) will be analyzed and reported separately.

Will be assessed using Kaplan-Meier estimates. OS for the main cohort and exploratory cohort will be analyzed and reported separately.

Will be assessed using Kaplan-Meier estimates. DOR for the main cohorts and exploratory cohort will be analyzed and reported separately.

Will be assessed using the National Cancer Institute, Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0.

National Cancer Institute (NCI)

Northwestern University

Cholangiocarcinoma

Biliary Tract Neoplasms

Biliary Tract Diseases

Bile Duct Cancer

Biliary Tract Cancer

Lenvatinib

Protein Kinase Inhibitors

Drug doses for BTC are identical, being orally administered at 8mg/d to patients weighing \<60 kg and 12mg/d to those ≥60 kg.

Hai-Tao Zhao, M.D.

This is a single center, nonrandom, open-label study aiming to evluate the efficacy and safety of lenvatinib for patients with pretreated advanced biliary tract cancer.

Lenvatinib targets VEGFR1, 2, and 3, PDGFRα, Fibroblast growth factor receptor (FGFR), and the KIT and RET tyrosine kinases and was initially developed for use in various tumor types. This is a single-center, non-random, open-label study in participants with unresectable BTC and disease progression or failure following at least one chemotherapy regimen. This study contains three procedures: a pre-treatment procedure that will last within 21 days; a treatment procedure that will consist of study treatment cycles and tumor assessment conducted every 6-8 weeks; and a follow-up procedure that will begin immediately after the off-treatment visit and will continue as long as the participant is alive, unless the participant withdraws consent, or until the terminal of the study.

Patients are confirmed with biliary tract cancers by imaging and histological examination and meet with the inclusive criteria, including intrahepatic cholangiocarcinoma, hilar cholangiocarcinoma, common bile duct cancer and gallbladder cancer.

Lenvatinib in Patients With Previously Treated Advanced Biliary Tract Cancer

The Efficacy and Safety of Lenvatinib in Patients With Previously Treated Advanced Biliary Tract Cancer

Clinical benefit rate (CBR) \[ Time Frame: From the date of first dose of study drug to the date of the first documentation of disease progression or death from any cause, whichever occurs first, or up to approximately 1 years \]

Overall survival (OS) \[ Time Frame: From the date of first dose of study drug to the date of death from any cause, or up to approximately 2 years \]

DCR is defined as the percentage of participants with complete response (CR) + partial response (PR) + stable disease (SD).

Treatment related adverse events (AEs) were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (CTCAE 4.0). The study recorded the occurrence rate of treatment related AEs

Peking Union Medical College Hospital

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
CPI-613 (Devimistat) in Combination With Hydroxychloroquine and 5-fluorouracil or Gemcitabine in Treating Patients With Advanced Chemorefractory Solid Tumors	NCT05733000	Advanced Biliar... Advanced Colore... Advanced Gastro... Advanced Lung A... Advanced Malign... Advanced Ovaria... Advanced Pancre... Advanced Urothe... Clinical Stage ... Clinical Stage ... Metastatic Bili... Metastatic Colo... Metastatic Gast... Metastatic Lung... Metastatic Ovar... Metastatic Panc... Metastatic Urot... Refractory Bili... Refractory Colo... Refractory Gast... Refractory Lung... Refractory Ovar... Refractory Panc... Refractory Urot... Stage II Pancre... Stage III Color... Stage III Lung ... Stage III Ovari... Stage III Pancr... Stage IV Colore... Stage IV Lung C... Stage IV Ovaria... Stage IV Pancre...	Biospecimen Col... Computed Tomogr... Devimistat Fluorouracil Gemcitabine Hyd... Hydroxychloroqu... Magnetic Resona...	18 Years -	Northwestern University
Lenvatinib in Patients With Previously Treated Advanced Biliary Tract Cancer	NCT04656249	Cholangiocarcin... Biliary Tract C... Targeted Therap...	Lenvatinib	18 Years -	Peking Union Medical College Hospital
Lenvatinib in Patients With Previously Treated Advanced Biliary Tract Cancer	NCT04656249	Cholangiocarcin... Biliary Tract C... Targeted Therap...	Lenvatinib	18 Years -	Peking Union Medical College Hospital

Spots Global Cancer Trial Database for refractory biliary tract carcinoma