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C04.588.274.476.411.307Phase 1NCT05070104

CPI-613 (Devimistat) in Combination With Modified FOLFIRINOX Plus Bevacizumab in Patients With Metastatic Colorectal Cancer

A Phase 1 study testing CPI-613, modified FFX and Bevacizumab in people with C04.588.274.476.411.307, run by Cornerstone Pharmaceuticals.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

Pre-clinical in vitro and in vivo data as well as early phase 1 clinical trials have shown that both hematologic and solid tumor cells are susceptible to single-agent cytotoxicity by CPI-613 (devimistat), consistent with its selective target of the altered form of mitochondrial energy metabolism in tumor cells… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
C04.588.274.476.411.307
What is being tested?
CPI-613, modified FFX and Bevacizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
30 Mar 2023to 1 Nov 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Written informed consent in accordance with federal, local, and institutional guidelines
  • Patients must have histologically/pathologically confirmed colorectal adenocarcinoma with measurable disease by RECIST 1.1 criteria
  • Patients must have had no prior chemotherapy for metastatic disease with fluoropyrimidine based chemotherapy with oxaliplatin or irinotecan
  • Patients with prior adjuvant chemotherapy are allowed, as long as a minimum of 6 months have passed between the completion of adjuvant therapy and the start of the study medication
  • Age >18 years
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
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  • Radiographic evidence of metastatic disease
  • At the time of study entry:
  • absolute neutrophil count must be ≥ 1000/mm3, hemoglobin ≥ 9 gm/dL, and platelet count ≥ 100,000/mm3 There must be evidence of adequate hepatic and renal function. Bilirubin must be ≤ 1.5 x upper limit of normal (ULN) for the lab unless the patient has a chronic grade 1 bilirubin elevation due to Gilbert's disease or similar syndrome due to slow conjugation of bilirubin Alkaline phosphatase must be ≤ 3 x ULN for the lab AST and ALT must be ≤ 5 x ULN for the lab Serum creatinine ≤ 1.5 x ULN for the lab Note: For patients with liver metastases, non-fasting bilirubin 1.5 x ULN to 3 x ULN of the institution's normal range are acceptable.
  • Both male and female patients with childbearing potential must agree to use adequatecontraception throughout the study and for 9 months after last dose of mFOLFIRINOX, bevacizumab or CPI-613 (devimistat)
  • Patients without liver metastasis are eligible if they have ALT and AST ≤ 3.0 x ULN

Who cannot join

  • Diagnosis of anal or small bowel carcinoma
  • Colorectal cancer other than adenocarcinoma, e.g., sarcoma, lymphoma, carcinoid
  • Patients with tumors that are MSI-high/dMMR
  • Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days ofreceiving study therapy
  • Active infection or chronic infection requiring systemic therapy
  • Known history of human immunodeficiency virus (HIV) or acquired immunodeficiencyrelated (AIDS) illnesses with CD4 count < 250 cells/mm3
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  • Any of the following cardiac conditions:
  • Documented NYHA Class III or IV congestive heart failure, Myocardial infarction within 6 months prior to study entry, Unstable angina within 6 months prior to study entry, Symptomatic arrhythmia
  • Other malignancies unless the patient is considered to be disease-free and has completed therapy for the malignancy ≥ 12 months prior to study entry.
  • Patients with the following cancers are eligible if diagnosed and treated within the past 12 months: carcinoma in situ of the cervix, and basal cell and squamous cell carcinoma of the skin
  • Psychiatric or addictive disorders or other conditions that in the opinion of the investigator would preclude the patient from meeting the study requirements or interfere with interpretation of study results
  • Any other chronic or clinically significant medical condition that in the opinion of investigator would jeopardize the safety or rights of the volunteer. Including, but not limited to: diabetes mellitus type I, chronic hepatitis; OR clinically significant forms of drug oralcohol abuse, asthma, autoimmune disease, psychiatric disorders, heart disease, or cancer. Patients must have neuropathy grade 1 or less
  • Pregnancy or lactation at the time of study entry
  • Use of any investigational agent within 4 weeks prior to the first dose study therapy
  • Patients with the following conditions:
  • Uncontrolled hypertension (defined as systolic blood pressure ≥ 150 mm Hg and diastolic blood pressure ≥ 100 mm Hg) Bleeding diatheses or hemorrhage within 6 months prior of study enrollment Gastrointestinal perforation or fistulas History of thromboembolic events Reversible Posterior Leukoencephalopathy Syndrome (RPLS), Proteinuria > 1gr/24 hours
  • Patients with current serious, non-healing wound, ulcer and baseline peripheral neuropathy of grade 2 or greater, hypersensitivity reaction to 5-FU, oxaliplatin or other platinum-based drugs, or irinotecan if it was previously administered in the adjuvant setting

About this study

Official title: Phase I Study of the First-In-Class Agent CPI-613 (Devimistat) in Combination With Modified FOLFIRINOX Plus Bevacizumab in Patients With Metastatic Colorectal Cancer

Pre-clinical in vitro and in vivo data as well as early phase 1 clinical trials have shown that both hematologic and solid tumor cells are susceptible to single-agent cytotoxicity by CPI-613 (devimistat), consistent with its selective target of the altered form of mitochondrial energy metabolism in tumor cells, causing changes in mitochondrial enzyme activities and redox status, which lead to apoptosis, necrosis, and autophagy of tumor cells leading to the death of cancer cells. It is our hypothesis that CPI-613 (devimistat) will enhance the efficacy of mFOLFIRINOX plus Bevacizumab when given as a combination treatment. The study will follow a standard 3+3 design. Cohorts of three to six patients will be treated at each dose level until the MTD is defined.

Being tested
CPI-613, modified FFX, Bevacizumab

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CPI-613Drug

    Also called Devimistat

    250-1000mg/m2 -14 day cycle

  • modified FFXDrug

    Irinotecan: 150mg/m2 IV over 90 min-14 day cycle Leucovorin: 400mg/m2 IV over 2hrs with Irinotecan-14 day cycle Oxaliplatin: 85mg/m2 IV over 2hrs-14 day cycle 5FU: 2400mg/m2 IV over 46-48 hrs-14 day cycle

  • BevacizumabDrug

    5mg/kg IV

Study groups in NCT05070104
Study groupRoleWhat they receive
Single ArmExperimentalCPI-613 mFFX Bevacizumab
Receives: Drug: CPI-613; Drug: modified FFX; Drug: Bevacizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety and tolerability

    Number of patients with Dose-limiting toxicities (DLT) will be assessed in order to be able to establish safety and tolerability for the combination of CPI-613, mFFX with bevacizumab therapy. Using the descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 for adverse event reporting (Grade 1 (Mild) - 5 (Death) as well as expectedness (unexpected/expected) and attribution (definitely related to study treatment to unrelated to study treatment).

    Measured: 3-6 months

  2. Safety and tolerability

    Dose-limiting toxicities assessed in order to be able to establish safety and tolerability for the combination of CPI-613, mFFX with bevacizumab therapy. Using the descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 for adverse event reporting (Grade 1 (Mild) - 5 (Death) as well as expectedness (unexpected/expected) and attribution (definitely related to study treatment to unrelated to study treatment).

    Measured: 3-6 months

  3. Recommended Phase 2 Dose

    Determine recommended phase 2 dose (RP2D) of CPI-613 (devimistat) (MTD) in combination with mFOLFIRINOX plus bevacizumab

    Measured: 3-6 months

Secondary outcomes (2)

  1. Objective Response Rate

    It is defined as the proportion of patients who achieve complete response or partial response during or following study treatment

    Measured: 3-12 months

  2. Overall Survival

    Defines as the time from enrollment to the date of death due to any cause.

    Measured: 3-12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Oct 2021
  2. Study start30 Mar 2023 (estimated)
  3. Primary completion1 Mar 2024 (estimated)
  4. Study completion1 Nov 2024 (estimated)

Why it stopped: no funding

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Single group, Open label
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05070104
Sponsor's protocol ID
ACHIEVE613
Status last verified
Sep 2023
First submitted
17 Sep 2021
Last updated
13 Sep 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing CPI-613, modified FFX and Bevacizumab in people with C04.588.274.476.411.307, run by Cornerstone Pharmaceuticals.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 13 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and tolerability (time frame: 3-6 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05070104.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2023.

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