Neoplasms

All Conditions

Digestive System Diseases

Rare Diseases

Cholangiocarcinoma

Biliary Tract Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Biliary Tract Diseases

Gastrointestinal Diseases

Bile Duct Cancer

Biliary Tract Cancer

Gallbladder Cancer

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Cisplatin

Antimetabolites

On Day 1 and Day 8 of each 3-week cycle, patients will receive CPI-613 + gemcitabine and cisplatin. Patients may continue gemcitabine, cisplatin and CPI-613 for up to 2 years in absence of disease progression or unacceptable toxicity.

On Day 1 and Day 8 of each 3-week cycle, patients will receive gemcitabine and cisplatin. Patients may continue gemcitabine and cisplatin for up to 2 years in absence of disease progression or unacceptable toxicity.

CPI 613

Vaibhav Sahai, MBBS, MS

The purpose of this research study is to determine the safety and efficacy of CPI-613 (devimistat) in the treatment of advanced biliary tract cancer when used in combination with standard of care chemotherapy (gemcitabine plus cisplatin) compared to gemcitabine plus cisplatin alone.

This research study has two parts:

In the phase 1 portion of this study, patients will receive a combination of CPI-613 and standard of care chemotherapy. Dose levels of CPI-613 will be adjusted to find the best dose, which will be the recommended phase 2 dose level.

In the phase 2 portion of this study, patients will be randomized into two arms. Patients in Arm A will receive the combination of the recommended dose level of CPI-613 and standard of care chemotherapy. Patients in Arm B will receive standard of care chemotherapy.

At the end of the study, researchers will compare the health outcomes of the patients that received CPI-613 + standard care to the outcomes of patients that received only standard care.

Phase II: 2:1 Randomization with Bayesian Design Control Arm

Gemcitabine and Cisplatin With or Without CPI-613 as First Line Therapy for Patients With Advanced Unresectable Biliary Tract Cancer (BilT-04)

A Multi-Center Randomized Phase IB/II Study of Gemcitabine and Cisplatin With or Without CPI-613 as First Line Therapy for Patients With Advanced Unresectable Biliary Tract Cancer (BilT-04)

Dose limiting toxicities will determine the maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D) of combination therapy with CPI-613 + gemcitabine and cisplatin. Assessed using the NCI CTCAE v5.0

Objective response assessment will be determined by review of CT or MR scans of the chest, abdomen and pelvis. ORR (Partial Response + Complete Response) will be assessed per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, during active study treatment. All enrolled patients who receive at least 1 cycle of therapy and have their disease re-evaluated will be considered evaluable for response. (Note: Patients who exhibit objective disease progression prior to the end of cycle 1 will also be considered evaluable.)

PFS will be determined from date of first study treatment until the date of radiological or clinical progression (leading to withdrawal from the study) or date of last disease evaluation (for patients without progression). It will be calculated using the product-limit method of Kaplan and Meier. All patients that receive at least one dose of study treatment will be considered evaluable.

From date of first study treatment until date of last disease evaluation or until death from any cause. Using the product-limit method of Kaplan and Meier.

To evaluate the safety of CPI-613 in combination with gemcitabine and cisplatin in this patient population, assessed using the Common Toxicity Criteria for Adverse Events (CTCAE) v5.0. All patients that receive at least one dose of study treatment will be considered evaluable.

University of Michigan Rogel Cancer Center

Blood and Lymph Conditions

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Sarcoma

Sarcoma, Myeloid

Neoplasms by Histologic Type

Hematologic Diseases

Neoplasms, Connective and Soft Tissue

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Soft Tissue Sarcoma

Acute Graft Versus Host Disease

Myeloid Sarcoma

Hypoglycemic Agents

Metformin

Induction therapy with CPI-613 and Metformin (ideally 2 hours prior to start of CPI-613 infusions on days 1-5) for two cycles of treatment.

Maintenance therapy with CPI-613 and Metformin (ideally 2 hours prior to start of CPI-613 infusions on days 1-5) until progression, intolerable toxicity of withdrawal of consent.

For INDUCTION therapy (14 day cycles): Devimistat (CPI-613) 2,500mg/m2, days 1-5, 14-day cycles for cycles 1 and 2 only.

For MAINTENANCE therapy (21 day cycles): Devimistat (CPI-613) 2,500mg/m2, days 1-5, 21-day cycles until progression, intolerable toxicity or withdrawal of consent.

For INDUCTION therapy (14 day cycles):

Metformin 500 mg daily (taken with meals), days 1-2 for cycle 1 only. Metformin 500 mg twice daily (taken with meals), days 3-14 for cycle 1 only. Metformin 1,000 mg daily (taken with meals), days 1-2 for cycle 2 only. Metformin 1,000 mg twice daily (taken with meals) days 3-4 for cycle 2 only.

For MAINTENANCE therapy (21 day cycles): Metformin 1,000 mg twice daily (taken with meals) days 1-21 until progression, intolerable toxicity or withdrawal of consent

In the first induction cycle ONLY, extra blood will be withdrawn on day 1 before and after treatment with CPI-613 research purposes. Additional blood draws on days 2-5 to test blood before receiving CPI-613 to make sure participants are healthy enough to receive CPI-613.

Blood draws

After the second induction cycle participants will have a bone marrow biopsy. After this biopsy, participants will have other bone marrow biopsies every 3 months for the next year. After the first year, participants may have a bone marrow biopsy if the treating physician feels it is necessary.

Bone marrow biopsy

Study Coodinator

Study Coordinator

Bayard Powell, MD

The purpose of this research study is to find out what effects (the good and bad) the combination treatment of metformin and CPI-613 has in treating participants with acute myeloid leukemia or granulocytic sarcoma that has either returned after treatment or did not respond to treatment.

Primary Objective: To establish the feasibility of delivering the combination of CPI-613 and metformin in patients with relapsed or refractory acute myeloid leukemia (AML).

Secondary Objectives: To determine the response rate of CPI-613 and metformin in relapsed or refractory AML defined as Complete remission (CR) + Complete remission with incomplete count recovery (CRi) + Morphologic Leukemia-Free State (MLFS).

* To determine the overall survival of patients with relapsed or refractory AML treated with CPI-613 and metformin.
* To determine the safety of CPI-613 and metformin in patients with relapsed or refractory acute myeloid leukemia (AML).

This is a Phase II, Simon's two-stage study evaluating the feasibility and effectiveness of combination CPI-613 and metformin in relapsed or refractory acute myeloid leukemia. The first stage will consist of 9 evaluable patients. If the study continues to stage 2, a total of 17 evaluable patients will be enrolled.

CPI-613 Given With Metformin in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML)

An Open Label, Pilot Phase II Study to Evaluate the Feasibility and Efficacy of CPI-613 Given With Metformin in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML)

Feasibility is defined as the ability to deliver at least 1 cycle of maintenance therapy in 50% or more of patients who complete induction therapy.

Efficacy will be assessed in the first 9 evaluable participants using a Simon's two-stage design to examine efficacy in terms of response where response is defined as:

* Complete remission (CR) (Bone marrow blasts, 5%; absence of circulating blasts; absence of extramedullary disease; ANC ≤ 1.0 × 109/L (1,000/μL); plate) or
* Complete remission with incomplete count recovery (CRi) (All CR criteria except for residual neutropenia \< 1.0 × 109/L (1,000/μL) or thrombocytopenia \< 100 × 109/L (100,000/μL) or
* Morphologically leukemia free state (MLFS) (Bone marrow blasts \< 5%; absence of circulating blasts; absence of extramedullary disease; no hematologic recovery required).

Overall survival is calculated in days from date of study treatment initiation to date of death due to any cause. Patients last known to be alive are censored at date of last contact.

Safety will be evaluated by describing the nature and frequency of adverse events as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

National Cancer Institute (NCI)

Cornerstone Pharmaceuticals

Wake Forest University Health Sciences

Gland and Hormone Related Diseases

Pancreatic Neoplasms

Endocrine Gland Neoplasms

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Micronutrients

Hematinics

Bone Density Conservation Agents

Vitamins

Irinotecan

Leucovorin

Fluorouracil

Levoleucovorin

Oxaliplatin

Calcium

Folic Acid

Folfirinox

Calcium, Dietary

Vitamin B Complex

Topoisomerase I Inhibitors

Enzyme Inhibitors

Antidotes

Protective Agents

Trace Elements

Folinic Acid

Folate

Vitamin B9

Novel drug and mitochondrial inhibitor, CPI-613 in conjunction with standard-of-care FOLFRINOX.

Consists of a Standard Dose Cohort and Dose escalation cohort using a standard 3 + 3 design starting at 750 mg/m\^2 given at a rate of 4 ml/min ("dose level (DL) 2"). Participants receiving a dose of 1000mg/m\^2 will be treated over 2 hours. In the absence of any DLT, the next DL will begin enrollment. If 1 DLT occurs, the DL will be expanded by 3 participants. If \<33% of participants experience a DLT, the next DL will be opened and will proceed in similarly. Only 2 DLs are expected to be studied: 750 mg/m\^2 and 1000 mg/m\^2.

Participants may be enrolled in this cohort after the accrual goal of the standard cohort is met but prior to the completion of treatment of all patients in the standard dose cohort

Participants experiencing a DLT will be allowed to continue on the study at the standard DL of 500 mg or lower.

Standard Dose Cohort: CPI-613, 500 mg/m2, IV infusion at a rate of 4 mL/min via a central venous port on days 1 and 3 of each cycle, every 2 weeks.

Dose Escalation Cohort: CPI-613, 750-1000 mg/m2 IV infusion at a rate of 3 mL/min via a central venous port on days 1 and 3 of each cycle, every 2 weeks.

Intended treatment protocol is 12 cycles (2 weeks each) or 6 months

Administered at 65 mg/m2 given as a 2-hr IV

Part of SOC mFOLFRINOX treatment combination of Oxaliplatin, Irniotecan, 5-flurouracil, and vitamin derivative (Folinic acid)

Administered at 140 mg/m2 given as a 90-min IV infusion) via a Y-connector

Part of SOC mFOLFRINOX treatment combination of Oxaliplatin, Irniotecan, 5-flurouracil, and vitamin derivative (Folinic acid)

Administered at 400 mg/m2 as bolus followed by a 46-hr infusion at 2400 mg/m2, starting immediately after completion of folinic acid and irinotecan

Part of SOC mFOLFRINOX treatment combination of Oxaliplatin, Irniotecan, 5-flurouracil, and vitamin derivative (Folinic acid)

5-flurouracil

Administered at 400 mg/m2 given as a 90-min infusion immediately after oxaliplatin

Part of SOC mFOLFRINOX treatment combination of Oxaliplatin, Irniotecan, 5-flurouracil, and vitamin derivative (Folinic acid)

Folinic acid

David Bajor, MD

The purpose of this study is to treat participants with the combination of CPI-613 (the study drug) with FOLFIRINOX (the standard combination of drugs) to determine if it is safe and effective for participants with localized and unresectable pancreatic cancer. This study is specifically for participants who have a pancreatic cancer that is localized and not considered resectable or removable by a surgeon, without additional treatment.

This is a single-arm study of participants with locally advanced pancreatic ductal adenocarcinoma evaluating combination CPI-613 with modified FOLFIRINOX, with the addition of a dose escalation cohort to assess safety. All study participants will get the same study intervention, which includes the best available treatment for locally advanced pancreatic cancer, plus an experimental therapy. The standard therapy is called mFOLFIRINOX, which is a combination of three chemotherapy drugs (Oxaliplatin, Irniotecan and 5-flurouracil) and one additional vitamin derivative (Folinic acid). The experimental drug is CPI-613, which inhibits energy production in cells, and early studies suggest that pancreatic cancer cells may be especially sensitive. Pre-treatment, diagnostic biopsy tissue will be collected when available, and clinical data will be evaluated to determine if the combination results in improved overall survival compared to historical experience. Based on new data, the study team will also attempt to identify a new maximum tolerated dose (MTD) of CPI-613 in a phase 1 open-label dose-regimen finding study.

The objectives of the Standard Dose Cohort are to determine the safety and efficacy of CPI-613, in combination with mFOLFIRINOX for locally advanced pancreatic cancer.

The objectives of the Dose Escalation Cohort is to determine a new maximum-tolerated dose (MTD) of CPI-613 when given in combination with mFOLFIRINOX.

Single-armed study of patients with locally advanced pancreatic cancer, evaluating combination CPI-613 with modified FOLFIRINOX

CPI-613 in Combination With Modified FOLFIRINOX in Locally Advanced Pancreatic Cancer

A Phase II/I Open-Label Clinical Trial of CPI-613 in Combination With Modified FOLFIRINOX in Patients With Locally Advanced Pancreatic Cancer and Good Performance Status

Interval between enrollment and death for participants for all participants.

Median OS will be estimated using the Kaplan-Meier method along with a two-sided 80% confidence interval (CI). OS will be documented and reported separately per cohort

MTD of CPI-613 when given in combination with mFOLFIRINOX in the added small cohort of participants with higher doses of CPI-613 developed to redefine MTD

Median (and 95% CI) time from study enrollment to progression or death from any cause for all participants.

Distribution of PFS will be estimated using the Kaplan-Meier method. Participants alive at the end of follow-up are censored. PFS will be documented and reported separately per cohort

Median (and 95% CI) time from enrollment to progression

Distribution of TTP will be estimated using the Kaplan-Meier method. Participants who die but have not progressed are censored.

RECIST version 1.1 response rates including complete response, partial response and stable disease (CR+PR+SD).

CRp defined as the proportion of participants that are designated having a complete response after treatment on protocol, evidenced by tissue samples taken during the subsequent resection

CRp is defined by the NCI as "the lack of all signs of cancer in tissue samples removed during surgery or biopsy after treatment with radiation or chemotherapy".

Resection margins are defined by the NCI as "The edge or border of the tissue removed in cancer surgery. The margin is described as negative or clean when the pathologist finds no cancer cells at the edge of the tissue, suggesting that all of the cancer has been removed. The margin is described as positive or involved when the pathologist finds cancer cells at the edge of the tissue, suggesting that all of the cancer has not been removed."

The rate of negative resection margins will be estimates with 95 % confidence intervals

Percent of participants previously determined to be borderline- or non-resectable that undergo complete surgical resection after treatment on protocol.

David Bajor

Immune System Diseases

Lymphoma

Lymphoma, T-Cell

Lymphoma, T-Cell, Peripheral

Lymphoma, Non-Hodgkin

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Peripheral T-cell Lymphoma

Bendamustine Hydrochloride

Antineoplastic Agents, Alkylating

Alkylating Agents

CPI-613 at 2500 mg/m2 is infused intravenously (IV) via a central catheter over 2 hrs on Days 1and 2. Bendamustine at 90 mg/m2 is infused IV over 10 minutes on Days 1 and 2 of each treatment cycle, given immediately after CPI-613 administration.

CPI-613 is to be given as 2-hr IV infusion via a central venous catheter. The starting dose of CPI-613 will be 2500 mg/m2 which was determined to be the MTD in the previous phase I clinical trial.

Bendamustine at 90 mg/m2 is infused by IV over 10 minutes on Days 1 and 2 of each treatment cycle. Bendamustine is given immediately after CPI-613 administration.

Bendamustine

Brittany Mabe, RN

Tong Chen, RN

Brittany Choi, RN

Rakhee Vaidya, MBBS

Rakhee Vaidya, M.B.B.S.

The purpose of this study is to determine if it is possible to give CPI-613 with the drug Bendamustine for 2 days every 28 days without causing severe side effects. In addition, this study will also test the safety of CPI-613 when given in combination with Bendamustine.

Primary Objectives: A pilot Study to evaluate the feasibility, safety and tolerability of a two day course per cycle of Bendamustine plus CPI-613 in patients with relapsed and refractory T cell non-hodgkin lymphoma.

Exploratory Objectives

To evaluate:

* Overall response rate (ORR) and disease control rate (DCR) derived from the Lugano classification.
* Duration of response (DOR) derived from the Lugano classification.
* Progression-Free-Survival (PFS) derived from Lugano classification.
* Overall Survival (OS).
* Single cell transcriptomics from PMBCs pre- and post-treatment; for correlative analyses of blood PBMC (and possibly excess pre-treatment tumor biopsy) cell population diversity and functional states to reveal potential mechanisms of drug treatment with regard to patient response status.

CPI-613 in Combination With Bendamustine in Patients With Relapsed/Refractory T-Cell Non-Hodgkin Lymphoma

Pilot Study of CPI-613, in Combination With Bendamustine, in Patients With Relapsed or Refractory T-Cell Non-Hodgkin Lymphoma

Feasibility will be defined as 75% of patients being successfully able to complete 80% of their therapy regimens. Toxicity data will be collected on all patients who receive at least one dose of treatment on the study

Overall response rate is defined as the proportion of patients who achieve a best overall response complete response or partial response during or following study treatment according to the Lugano Classification (Stage I - involvement in a single lymph node region to Stage IV diffuse or disseminated involvement of one or more extranodal organs or tissue).

Disease control rate defined as the proportion of patients who achieve a best overall response of complete response, partial response, or stable disease (SD). Best overall response of stable disease must have met the response stable disease criteria at least once ≥12 weeks after start of study treatment.

Duration of Response will be defined for responders (patients with a best overall response of complete response or partial response). It is the time from the date of the first documented complete response or partial response until the date of the first date of progressive disease, or death due to any cause, whichever occurs first. If a patient has not progressed or died by the analysis cutoff date, duration of response will be censored at the time of the last adequate tumor assessment on or before the cutoff date.

Progression free survival defined as the time from the start of study treatment until the first date of progressive disease, or death due to any cause, whichever occurs first. If a patient has not progressed or died by the analysis cutoff date, progression free survival will be censored at the time of the last adequate tumor assessment on or before the cutoff date.

Overall survival is measured from the start of study treatment until death due to any cause. If a patient is not known to have died at the date of the analysis cut-off, overall survival will be censored at the last date that: Patient is documented to be alive. At the time of single cell sequencing.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Gemcitabine and Cisplatin With or Without CPI-613 as First Line Therapy for Patients With Advanced Unresectable Biliary Tract Cancer (BilT-04)	NCT04203160	Biliary Tract C...	CPI 613 Gemcitabine Cisplatin	18 Years -	University of Michigan Rogel Cancer Center
CPI-613 Given With Metformin in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML)	NCT05854966	Acute Myeloid L... Acute Myeloid L... Granulocytic Sa...	CPI 613 Metformin Blood draws Bone marrow bio...	18 Years -	Wake Forest University Health Sciences
CPI-613 in Combination With Modified FOLFIRINOX in Locally Advanced Pancreatic Cancer	NCT03699319	Pancreatic Canc...	CPI 613 Oxaliplatin Irinotecan 5-flurouracil Folinic acid	18 Years - 80 Years	Case Comprehensive Cancer Center
CPI-613 in Combination With Bendamustine in Patients With Relapsed/Refractory T-Cell Non-Hodgkin Lymphoma	NCT04217317	Relapsed T-Cell... Refractory T-Ce... Non Hodgkin Lym...	CPI 613 Bendamustine	18 Years -	Wake Forest University Health Sciences
CPI-613 in Combination With Modified FOLFIRINOX in Locally Advanced Pancreatic Cancer	NCT03699319	Pancreatic Canc...	CPI 613 Oxaliplatin Irinotecan 5-flurouracil Folinic acid	18 Years - 80 Years	Case Comprehensive Cancer Center

Spots Global Cancer Trial Database for cpi 613

Every month we try and update this database with for cpi 613 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for cpi 613

Every month we try and update this database with for cpi 613 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for cpi 613 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.