CancerPhase 2NCT01832857
Phase 2 Safety, Tolerability and Efficacy Study of CPI-613 in Cancer Patients
A Phase 2 study testing CPI-613 in people with Cancer, run by Cornerstone Pharmaceuticals at 1 site in United States.
Trial summary
This Phase II study is conducted to assess the safety and efficacy of CPI-613 in patients with advanced and/or metastatic solid tumors for whom there there is no available therapy to provide clinical benefit or for those who have refused further standard therapy. The primary outcome measure is Overall Survival (OS). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer
- What is being tested?
- CPI-613
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2013to Dec 2016
- Phase
- Phase 2
- 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
- Patients must have advanced and/or metastatic, histologically or cytologically documented solid tumors, for whom there is no available therapy shown to provide clinical benefit or for those who have refused further standard therapy
- Eastern Cooperative Oncology Group (ECOG) performance status being 0-2
- Expected survival >3 months
- 18 years of age or older of both genders
- Women of child-bearing potential must use accepted contraceptive methods (abstinence, intrauterine device [IUD], oral contraceptive or double barrier device) during the study, and must have a negative serum or urine pregnancy test within 1 week prior to treatment initiation.
- Fertile men must practice effective contraceptive methods during the study, unless documentation of infertility exists
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- Mentally competent, with an ability to understand and willingness to sign the informed consent form
- No radiotherapy, treatment with cytotoxic agents (except CPI-613), or treatment with biologic agents within 3 weeks prior to treatment with CPI-613. At least 2 weeks must have elapsed from any prior surgery or hormonal therapy. Patients must have fully recovered from the acute toxicities of any prior treatment with any anti-cancer drugs, radiotherapy or other anti-cancer modalities (returned to baseline status as noted before most recent treatment). Patients with persisting, stable chronic toxicities from prior treatment ≤Grade 1 are eligible, but must be documented as such.
- Laboratory values ≤2 weeks must be:
- Adequate hematologic (white blood cell [WBC] ≥3500 cells/mm3 or ≥3.5 bil/L; platelet count ≥150,000 cells/mm3 or ≥150 bil/L; absolute neutrophil count [ANC] ≥1500 cells/mm3 or ≥1.5 bil/L; and hemoglobin (Hgb) ≥9 g/dL or ≥90 g/L).
- Adequate hepatic function (aspartate aminotransferase [AST/SGOT] ≤3x upper normal limit [UNL], alanine aminotransferase [ALT/SGPT] ≤3x UNL (≤5x UNL if liver metastases present), bilirubin ≤1.5x UNL).
- Adequate renal function (serum creatinine ≤2.0 mg/dL or 177 μmol/L, and blood urea nitrogen [BUN] ≤25 mg/dL).
- Adequate coagulation ("International Normalized Ratio or INR must be ≤1.5")
Who cannot join
- Serious medical illness
- Any active uncontrolled bleeding or patients with a bleeding diathesis
- Patients with active central nervous system (CNS) or epidural tumor
- Pregnant women, or women of child-bearing potential not using reliable means of contraception
- Lactating females
- Fertile men unwilling to practice contraceptive methods during the study period
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- Life expectancy less than 3 months
- Unwilling or unable to follow protocol requirements
- Dyspnea with minimal to moderate exertion, or patients with pleural, pericardial, or peritoneal effusions
- Active heart disease including but not limited to symptomatic congestive heart failure, symptomatic coronary artery disease, symptomatic angina pectoris, symptomatic myocardial infarction, arrhythmias requiring medication, or symptomatic congestive heart failure.
- A marked baseline prolongation of QT/QTc interval; a history of additional risk factors for torsade de pointes.
- Requirement for immediate palliative treatment of any kind including surgery
- Any condition or abnormality which may, in the opinion of the investigator, compromise the safety of patients
- Albumin <2.5 g/dL or <25 g/L
- Evidence of active infection, or serious infection, with the past month
- Patients with known HIV infection.
- Patients receiving any other standard or investigational treatment for their cancer, or any other investigational agent for any indication within the past 3 weeks prior to initiation of CPI-613 treatment.
- Patients who have received immunotherapy of any type within the past 4 weeks prior to initiation of CPI-613 treatment
- Patients that have received a chemotherapy regimen with stem cell support in the previous 6 months
- Troponin I above institution limit of normal
Trial locations and contacts
1 site in 1 country.
United States1 site
Eastchester Center for Cancer Care
The Bronx, New York, 10469
About this study
Official title: An Open Label, Phase 2 Trial to Evaluate the Safety, Tolerability and Efficacy of CPI-613 in Cancer Patients
This Phase II study is conducted to assess the safety and efficacy of CPI-613 in patients with advanced and/or metastatic solid tumors for whom there there is no available therapy to provide clinical benefit or for those who have refused further standard therapy. The primary outcome measure is Overall Survival (OS). The secondary outcome measures are: Response Rate (RR), Progression-Free Survival (PFS), and safety.
Read the detailed description
Open-Label Single-Arm Design: This is an open-label study, and investigators and subjects are not blinded to the treatment. Also, the assignment of patients will not be randomized, since this is a single-arm study.
Treatment with CPI-613: A treatment cycle is 4 weeks, with CPI-613 given on Days 1 and 4 of the first 3 weeks.
Dose and Sample Size: The dose of CPI-613 is 3,000 mg/m2. This is Maximum Tolerated Dose (MTD) determined from the Phase I dose-escalated trial, Study# CL-CPI-613-009 (conducted in patients with hematologic malignancies under IND 107,800). This dose has also been found to be well tolerated in another Phase I dose-escalated trial, Study# CL-CPI-613-002 (conducted in patients with solid tumor under IND 74,530). There will be 20 evaluable patients with each tumor type. Once there are 20 evaluable patients with a particular tumor type has been treated with at least 1 cycle, no patients of the same tumor type will be accrued. Dosing Delay and Dose Modification of CPI-613 in the Event of Adverse Events: For adverse events unrelated to serum creatinine elevation or reduction in renal function but are possibly related to CPI-613, the occurrence of Grade 1 toxicity does not generally require dose modification for subsequent doses for that patient. However, if Grade 2 toxicity (other than alopecia and nausea) probably related to CPI-613 develops, treatment is to be withheld and can resume only after the Grade 2 toxicity has been reduced to Grade 1 or below, and the dose level for subsequent doses for that patient will be reduced by 25% of the dose at which such Grade 2 toxicity occurs. Grade 2 alopecia and nausea do not require withholding treatment or dose reduction. If Grade 3 or 4 toxicity probably related to CPI-613 develops, dosing of CPI-613 of that patient will be withheld and the patient shall be monitored for recovery from, and reversibility of, such Grade 3 or 4 toxicity. To resume treatment with CPI-613 for a patient who has had CPI-613-related Grade 3 or 4 toxicity, the Grade 3 or 4 toxicity must be reduced to Grade 1 or below, and the dose level for subsequent doses for that patient will be reduced to 50% of the dose at which such Grade 3 or 4 toxicity occurs.
For adverse events related to creatinine elevation or reduction in renal function that are possibly related to CPI-613, dosing of the patient will be withheld even if the severity level is Grade 1 or above. Treatment can resume only after the toxicity has been reduced to Grade 0. The dose level for subsequent doses for that patient will be reduced by 15% if the severity level is of Grade 1, by 25% for Grade 2 toxicity, and by 50% for Grade 3 or 4 toxicity.
Furthermore, if the toxicity possibly related to CPI-613 is acute renal failure and the severity level is Grade 3 or 4, further patient enrollment will be temporarily suspended in order to enable assessment of the following aspects of the trial and implementation of corrective measures or protocol amendment, and if necessary:
- compliance of the study sites and investigators to the study protocol
- evaluation of the appropriateness of the procedures for monitoring renal function
- Conditions
- Cancer
- Being tested
- CPI-613
- Keywords
- metastatic, advanced, solid tumor, cancer, colon cancer, hepatocellular carcinoma, breast cancer, lung cancer, gastric cancer, esophageal cancer
- Medical subject headings
- Neoplasms, Neoplasm Metastasis, Colonic Neoplasms, Carcinoma, Hepatocellular, Breast Neoplasms, Lung Neoplasms, Stomach Neoplasms, Esophageal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CPI-613Drug
Also called 6,8-bis-benzylsulfanyloctanoic acid, 6,8-bis(benzylthio)octanoic acid, 6,8-bis-benzylsulfonyloctanoic acid, Bylantra (tentative)
CPI-613 drug product, provided in concentrated form at 50 mg/mL, must be diluted with D5W prior to administration. CPI-613 is to be infused intravenously (IV) via a central venous catheter. CPI-613 will be given 2x weekly, administered on Days 1 and 4 of each of the 3 treatment weeks, followed by a week of rest. The dose of CPI-613 will be 3,000 mg/m2 infused IV over 2 hours (this is the maximum tolerated dosing [MTD]), via a central venous catheter with D5W running at a rate of about 125-150 mL/hr.
| Study group | Role | What they receive |
|---|---|---|
| CPI-613 Alone | Experimental | This arm is for patients that have failed, or are not eligible for, all available therapies. CPI-613 drug product, provided in concentrated form at 50 mg/mL, must be diluted with D5W prior to administration. CPI-613 is to be infused intravenously (IV) via a central venous catheter. CPI-613 will be given 2x weekly, administered on Days 1 and 4 of each of the 3 treatment weeks, followed by a week of rest. The dose of CPI-613 will be 3,000 mg/m2 infused IV over 2 hours (this is the maximum tolerated dosing [MTD]), via a central venous catheter with D5W running at a rate of about 125-150 mL/hr. Receives: Drug: CPI-613 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival (OS)
Measured: Monitored until participants pass away, for an expected average of 6 months.
Secondary outcomes (3)
Progression-Free Survival (PFS)
Measured: Monitored during treatment with CPI-613 and until participants passed away, which will be an expected average of 6 months.
Safety
Safety assessment will be based on clinical signs, vital signs, blood work, adverse events (AEs), serious adverse events (SAEs), etc.
Measured: Monitored just before study treatment, and during study treatment at the end of every 4-week treatment cycle, for an expected average of 20 weeks.
Response Rate
Measured: Monitored at the end of every 4-week treatment cycle during treatment with CPI-613, for an expected average of 20 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Apr 2013 (estimated)
- Study startJun 2013
- Primary completionDec 2016
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cornerstone Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- King C Lee, Ph.D., Study chair, Cornerstone Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01832857
- Sponsor's protocol ID
- CL-CPI-613-023
- Status last verified
- Dec 2016
- First submitted
- 12 Apr 2013
- Last updated
- 29 Dec 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Liu N, Yan M, Tao Q, Wu J, Chen J, Chen X, Peng C. Inhibition of TCA cycle improves the anti-PD-1 immunotherapy efficacy in melanoma cells via ATF3-mediated PD-L1 expression and glycolysis. J Immunother Cancer. 2023 Sep;11(9):e007146. doi: 10.1136/jitc-2023-007146.
PubMed 37678921
Study at a glance
From the registry record, last updated by the sponsor on 29 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label, Phase 2 Trial to Evaluate the Safety, Tolerability and Efficacy of CPI-613 in Cancer Patients
- ClinicalTrials.gov ID
- NCT01832857
- Acronym / sponsor ID
- CL-CPI-613-023
- Conditions
- Cancer
- Keywords
- metastatic, advanced, solid tumor, cancer, colon cancer, hepatocellular carcinoma, breast cancer, lung cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Cornerstone PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Jun 2013
- Primary completion
- Dec 2016 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 16 Apr 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This Phase II study is conducted to assess the safety and efficacy of CPI-613 in patients with advanced and/or metastatic solid tumors for whom there there is no available therapy to provide clinical benefit or for those who have refused further standard therapy. The primary outcome measure is Overall Survival (OS). The secondary outcome measures are: Response Rate (RR), Progression-Free Survival (PFS), and safety.
Detailed description
Open-Label Single-Arm Design: This is an open-label study, and investigators and subjects are not blinded to the treatment. Also, the assignment of patients will not be randomized, since this is a single-arm study.
Treatment with CPI-613: A treatment cycle is 4 weeks, with CPI-613 given on Days 1 and 4 of the first 3 weeks.
Dose and Sample Size: The dose of CPI-613 is 3,000 mg/m2. This is Maximum Tolerated Dose (MTD) determined from the Phase I dose-escalated trial, Study# CL-CPI-613-009 (conducted in patients with hematologic malignancies under IND 107,800). This dose has also been found to be well tolerated in another Phase I dose-escalated trial, Study# CL-CPI-613-002 (conducted in patients with solid tumor under IND 74,530). There will be 20 evaluable patients with each tumor type. Once there are 20 evaluable patients with a particular tumor type has been treated with at least 1 cycle, no patients of the same tumor type will be accrued. Dosing Delay and Dose Modification of CPI-613 in the Event of Adverse Events: For adverse events unrelated to serum creatinine elevation or reduction in renal function but are possibly related to CPI-613, the occurrence of Grade 1 toxicity does not generally require dose modification for subsequent doses for that patient. However, if Grade 2 toxicity (other than alopecia and nausea) probably related to CPI-613 develops, treatment is to be withheld and can resume only after the Grade 2 toxicity has been reduced to Grade 1 or below, and the dose level for subsequent doses for that patient will be reduced by 25% of the dose at which such Grade 2 toxicity occurs. Grade 2 alopecia and nausea do not require withholding treatment or dose reduction. If Grade 3 or 4 toxicity probably related to CPI-613 develops, dosing of CPI-613 of that patient will be withheld and the patient shall be monitored for recovery from, and reversibility of, such Grade 3 or 4 toxicity. To resume treatment with CPI-613 for a patient who has had CPI-613-related Grade 3 or 4 toxicity, the Grade 3 or 4 toxicity must be reduced to Grade 1 or below, and the dose level for subsequent doses for that patient will be reduced to 50% of the dose at which such Grade 3 or 4 toxicity occurs.
For adverse events related to creatinine elevation or reduction in renal function that are possibly related to CPI-613, dosing of the patient will be withheld even if the severity level is Grade 1 or above. Treatment can resume only after the toxicity has been reduced to Grade 0. The dose level for subsequent doses for that patient will be reduced by 15% if the severity level is of Grade 1, by 25% for Grade 2 toxicity, and by 50% for Grade 3 or 4 toxicity.
Furthermore, if the toxicity possibly related to CPI-613 is acute renal failure and the severity level is Grade 3 or 4, further patient enrollment will be temporarily suspended in order to enable assessment of the following aspects of the trial and implementation of corrective measures or protocol amendment, and if necessary:
- compliance of the study sites and investigators to the study protocol
- evaluation of the appropriateness of the procedures for monitoring renal function
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CPI-613 Alone | Experimental | Drug: CPI-613This arm is for patients that have failed, or are not eligible for, all available therapies. CPI-613 drug product, provided in concentrated form at 50 mg/mL, must be diluted with D5W prior to administration. CPI-613 is to be infused intravenously (IV) via a central venous catheter. CPI-613 will be given 2x weekly, administered on Days 1 and 4 of each of the 3 treatment weeks, followed by a week of rest. The dose of CPI-613 will be 3,000 mg/m2 infused IV over 2 hours (this is the maximum tolerated dosing [MTD]), via a central venous catheter with D5W running at a rate of about 125-150 mL/hr. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Patients must have advanced and/or metastatic, histologically or cytologically documented solid tumors, for whom there is no available therapy shown to provide clinical benefit or for those who have refused further standard therapy
- Eastern Cooperative Oncology Group (ECOG) performance status being 0-2
- Expected survival >3 months
- 18 years of age or older of both genders
- Women of child-bearing potential must use accepted contraceptive methods (abstinence, intrauterine device [IUD], oral contraceptive or double barrier device) during the study, and must have a negative serum or urine pregnancy test within 1 week prior to treatment initiation.
Key exclusion criteria (20 listed)
- Serious medical illness
- Any active uncontrolled bleeding or patients with a bleeding diathesis
- Patients with active central nervous system (CNS) or epidural tumor
- Pregnant women, or women of child-bearing potential not using reliable means of contraception
- Lactating females
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CPI-613Also: 6,8-bis-benzylsulfanyloctanoic acid, 6,8-bis(benzylthio)octanoic acid, 6,8-bis-benzylsulfonyloctanoic acid, Bylantra (tentative)CPI-613 drug product, provided in concentrated form at 50 mg/mL, must be diluted with D5W prior to administration. CPI-613 is to be infused intravenously (IV) via a central venous catheter. CPI-613 will be given 2x weekly, administered on Days 1 and 4 of each of the 3 treatment weeks, followed by a week of rest. The dose of CPI-613 will be 3,000 mg/m2 infused IV over 2 hours (this is the maximum tolerated dosing [MTD]), via a central venous catheter with D5W running at a rate of about 125-150 mL/hr. | Drug | CPI-613 Alone |
Primary outcome
Overall Survival (OS)
Time frame: Monitored until participants pass away, for an expected average of 6 months.
3 secondary outcomes
Progression-Free Survival (PFS)
Time frame: Monitored during treatment with CPI-613 and until participants passed away, which will be an expected average of 6 months.
Safety
Time frame: Monitored just before study treatment, and during study treatment at the end of every 4-week treatment cycle, for an expected average of 20 weeks.
Response Rate
Time frame: Monitored at the end of every 4-week treatment cycle during treatment with CPI-613, for an expected average of 20 weeks.
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Dec 2016.
- Derived from this study: PubMed 37678921Liu N, Yan M, Tao Q, Wu J, Chen J, Chen X, Peng C. Inhibition of TCA cycle improves the anti-PD-1 immunotherapy efficacy in melanoma cells via ATF3-mediated PD-L1 expression and glycolysis. J Immunother Cancer. 2023 Sep;11(9):e007146. doi: 10.1136/jitc-2023-007146.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
King C Lee, Ph.D. study chair
Cornerstone Pharmaceuticals
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CPI-613 in people with Cancer, run by Cornerstone Pharmaceuticals at 1 site in United States.
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 13 inclusion and 20 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: stopped early, as of the sponsor's last update on 29 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 stopped early. Results are not available in the source record.
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?
Overall Survival (OS) (time frame: Monitored until participants pass away, for an expected average of 6 months.). 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 NCT01832857, which also lists 1 linked publication.
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 29 Dec 2016.