Colorectal CancerPhase 1/2NCT02861300
CB-839 + Capecitabine in Solid Tumors and Fluoropyrimidine Resistant PIK3CA Mutant Colorectal Cancer
A Phase 1/2 study testing CB-839 and Capecitabine in people with Colorectal Cancer and Colon Cancer, run by David Bajor, MD at 2 sites in United States.
Trial summary
This study has two portions. The main goal of the Phase I portion of this research study is to see what doses of CB-839 and capecitabine can safely be given to patients without having too many side effects. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Colorectal Cancer, Colon Cancer, Rectal Cancer
- What is being tested?
- CB-839 and Capecitabine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 2 sitesUnited States
- Study dates
- 12 Sep 2016to 10 Jan 2023
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Phase I
- Patients must have an advanced solid tumors for whom there are no remaining treatment options or colorectal patients who have progressed on front-line fluoropyrimidine containing therapy. Patients with colorectal cancer must have progressed on at least one line of fluoropyrimidine containing therapy. Receipt of either oxaliplatin or irinotecan in combination with a fluoropyrimidine is required in the front line setting for all colorectal cancer patients unless either of these agents are otherwise contraindicated in the opinion of the treating physician. Prior regorafenib or TAS-102 therapy is not required.
- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- Patients must have normal organ and marrow function as defined below:
- Hemoglobin ≥ 9.0 g/dl
- Leukocytes ≥ 3,000/mcL
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- Absolute neutrophil count ≥ 1,500/mcL
- Platelet count ≥ 100,000/mcL
- Serum creatinine ≤ 1.5 X institutional upper limit of normal
- Total bilirubin ≤ 1.5mg/dL
- Aspartate Aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT) ≤ 2.5 X institutional upper limit of normal
- Alanine Aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT) ≤ 2.5 x institutional upper limit of normal
- Patients must be able to swallow pills.
- Patients must have the ability to understand and the willingness to sign a written informed consent document.
- Female patients of childbearing potential must have a negative serum or urine pregnancy test within 3 days prior to the first dose of study drug and agree to use dual methods of contraception during the study and for a minimum of 3 months following the last dose of study drug. Post-menopausal females (>45 years old and without menses for >1 year) and surgically sterilized females are exempt from these requirements. Male patients must use an effective barrier method of contraception during the study and for a minimum of 3 months following the last dose of study drug if sexually active with a female of childbearing potential.
- Phase II
- Patients must have histologically or cytologically confirmed, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutant metastatic colorectal cancer. PIK3CA status must be confirmed by tumor sequencing in a CLIA certified lab.
- Patients must have measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria that is amenable to biopsy and be willing to undergo pre- and post-treatment tumor biopsies. Lesions to be biopsied do not have to be those used for measurement.
- Patients must have received and progressed on fluoropyrimidine or fluoropyrimidine based therapy. Receipt of either oxaliplatin or irinotecan in combination with a fluoropyrimidine is required in the front line setting unless either of these agents are otherwise contraindicated in the opinion of the treating physician in which case a fluoropyrimidine only may be used. Prior regorafenib or TAS-102 therapy is not required.
- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
- Patients must have normal organ and marrow function as defined below:
- Hemoglobin ≥ 9.0 g/dl
- Leukocytes ≥ 3,000/mcL
- Absolute neutrophil count ≥ 1,500/mcL
- Platelet count ≥ 100,000/mcL
- Serum creatinine within normal institutional limits
- Total bilirubin ≤ 1.5 mg/dL
- AST (SGOT) ≤ 2.5 X institutional upper limit of normal
- ALT (SGPT) ≤ 2.5 x institutional upper limit of normal
- Patients must be able to swallow pills.
- Patients must have the ability to understand and the willingness to sign a written informed consent document.
- Female patients of childbearing potential must have a negative serum or urine pregnancy test within 3 days prior to the first dose of study drug and agree to use dual methods of contraception during the study and for a minimum of 3 months following the last dose of study drug. Post-menopausal females (>45 years old and without menses for >1 year) and surgically sterilized females are exempt from these requirements. Male patients must use an effective barrier method of contraception during the study and for a minimum of 3 months following the last dose of study drug if sexually active with a female of childbearing potential.
Who cannot join
- Both Phase I and Phase II
- Patients with ongoing toxicities > grade 1 according to National Cancer Institute (NCI) Common Terminology Criteria For Adverse Events (CTCAE) Version 4.0 (excluding alopecia) due to prior anti-cancer therapy.
- Patients receiving any other investigational agents or whom have received recent treatment for colorectal cancer (radiation within the previous two weeks, chemotherapy or investigational therapy within the previous four weeks).
- Patients with untreated brain metastases/central nervous system disease will be excluded due to their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- Patients with a history of allergic reactions attributed to or intolerance to compounds of similar chemical or biologic composition to either CB-839 or capecitabine. If capecitabine has been received previously, must have tolerated at least an equivalent dose to the dose to be administered at their assigned dose level.
- Patients who are unable to swallow pills or who have undergone surgery that prohibits the absorption of pills in the stomach.
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- Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris or myocardial infarction within prior 6 months, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Patients who are pregnant or breastfeeding will be excluded from the study.
- Patients known to be HIV positive who are not receiving anti-retroviral therapy will be excluded due to the marrow suppressive therapy involved in administration of the study treatment.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
Cleveland, Ohio, 44106
Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center
Cleveland, Ohio, 44195
About this study
Official title: Phase I/II Study of CB-839 and Capecitabine in Patients With Advanced Solid Tumors and Fluoropyrimidine Resistant PIK3CA Mutant Colorectal Cancer
This study has two portions. The main goal of the Phase I portion of this research study is to see what doses of CB-839 and capecitabine can safely be given to patients without having too many side effects. Other purposes of this research study will be to determine what side effects are seen with this combination of medicines. The Phase II portion of the study will test how many patients show shrinkage in their tumor with this combination of medicines and what changes occur inside the cancer cells and blood cells after treatment.
Read the detailed description
Phase I Primary Objective:
To determine the safety, tolerability and recommended phase II dose (RP2D) of combination CB-839 and capecitabine chemotherapy in patients with advanced solid tumors for whom there are no remaining treatment options or for whom single agent capecitabine is an acceptable therapy.
Phase II Primary Objective:
To determine the disease control rate of combination CB-839 and capecitabine chemotherapy in patients with metastatic PIK3CA mutant colorectal cancers who are refractory to fluoropyrimidine based therapy.
Phase I Secondary Objectives:
To determine the dose-limiting toxicities and maximum tolerated dose of combination therapy with CB-839 and capecitabine in patients with advanced solid tumors for whom there are no remaining treatment options or for whom single agent capecitabine is an acceptable therapy.
To determine the disease control rate as assessed by RECIST criteria of combination therapy with CB-839 and capecitabine in patients with advanced solid tumors for whom there are no remaining treatment options or for whom single agent capecitabine is an acceptable therapy.
Phase II Secondary Objectives:
To determine the progression free survival following treatment with CB-839 and capecitabine chemotherapy in patients with metastatic PIK3CA mutant colorectal cancer and are refractory to fluoropyrimidine therapy.
To determine the overall survival following treatment with CB-839 and capecitabine chemotherapy in patients who have metastatic PIK3CA mutant colorectal cancer and are refractory to fluoropyrimidine therapy.
- Conditions
- Colorectal Cancer, Colon Cancer, Rectal Cancer, Solid Tumor
- Being tested
- CB-839, Capecitabine
- Keywords
- CB-839, PIK3CA, capecitabine
- Medical subject headings
- Colorectal Neoplasms, Colonic Neoplasms, Rectal Neoplasms, Hereditary Sensory and Autonomic Neuropathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CB-839Drug
Patients will receive CB-839 orally twice daily during each cycle. Each cycle will be 21 days long. Disease assessment will occur after cycle 3.
CapecitabineDrug
Also called Xeloda
capecitabine will be given orally twice daily for 14-21 days of cycles. Each cycle will be 21 days long. Disease assessment will occur after cycle 3.
| Study group | Role | What they receive |
|---|---|---|
| CB-839 + capecitabine | Experimental | Patients will receive CB-839 orally twice daily for 21 days (continuous administration) and capecitabine orally twice daily for 14/21 days. In the phase I portion of the study, patients will receive escalating doses of CB-839 and capecitabine and will have day 15 blood samples drawn and archived for as needed assessment of CB-839 pharmacokinetics. In the phase II portion of the study, patients will receiving 800mg CB-839 and 1000mg/m^2 capecitabine as were determined to be safe doses during the phase I portion of the study. They will also undergo pre-treatment and post-treatment blood samples and tissue biopsies for evaluation of pharmacodynamic biomarkers. Receives: Drug: CB-839; Drug: Capecitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
PHASE I: Recommended Dose for Phase II Study
The Phase I study has been designed to define the recommended phase II dose of CB-839 and capecitabine. A traditional 3+3 dose escalation design will be adopted. Nine to twenty-four patients are expected to be enrolled, depending on the number of dose escalations and assuming that a total of 6 patients will be treated at the final recommended phase II dose level. Patients who complete the first 21 day treatment cycle of CB-839 and capecitabine chemotherapy will be included in the analysis.
Measured: At least 21 days of treatment
PHASE II: Progression-free Survival (PFS)
The number of participants that achieved PFS will be analyzed. Progression free survival (PFS) on combination CB-839 and capecitabine as determined by clinical assessment and RECIST criteria in patients with metastatic PIK3CA mutant colorectal cancer who are refractory to fluoropyrimidine based therapy. Progression free survival is defined as the time from randomization to documented progression or death without progression.
Measured: 6 months
Secondary outcomes (4)
PHASE I: Proportion of Patient Who Respond to Treatment
Disease control rate will be determined using RECIST criteria.
RECIST response categories: Progressive disease (PD): >=20% increase in sum of longest diameter (LD) of target lesion(s), taking as reference smallest sum LD recorded since treatment started. Complete response (CR): disappearance of all target lesions. Partial response (PR): >=30% decrease in sum of LD of target lesion(s), taking as reference baseline sum LD. Stable disease (SD): neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD.
Measured: At least 21 days of treatment
PHASE I: Dose-limiting Toxicities
Phase I: Dose-limiting toxicities as assessed by CTCAE version 4 of combination CB-839 and capecitabine in patients with advanced solid tumors with no remaining treatment options or patients for whom single agent capecitabine is an acceptable therapy
Measured: Up to 18 months after beginning treatment
PHASE II: Number of Patients With Response to Treatment
In the phase II component of this study, the primary endpoint is response rate. Disease control rate will be determined using RECIST criteria.
RECIST response categories: Progressive disease (PD): >=20% increase in sum of longest diameter (LD) of target lesion(s), taking as reference smallest sum LD recorded since treatment started. Complete response (CR): disappearance of all target lesions. Partial response (PR): >=30% decrease in sum of LD of target lesion(s), taking as reference baseline sum LD. Stable disease (SD): neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD.
Measured: Up to 18 months after beginning treatment
PHASE II: Overall Survival
The number of participants to achieve overall survival will be analyzed. Overall survival of patients with metastatic PIK3CA mutant colorectal cancer who are refractory to fluoropyrimidine based therapy following treatment with CB-839 and capecitabine chemotherapy. Overall survival is defined as the time from randomization to death from any cause.
Measured: Up to 18 months after beginning treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2016 (estimated)
- Study start12 Sep 2016
- Primary completion10 Jan 2023
- Study completion10 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Colorectal 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- David Bajor, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, David Bajor, MD, Case Comprehensive Cancer Center
- Investigators
- David Bajor, MD, Principal investigator, University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02861300
- Sponsor's protocol ID
- CASE1216
- Status last verified
- Dec 2024
- First submitted
- 5 Aug 2016
- Last updated
- 19 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Sridhar SK, Abass KS, Gowthami B, Naveen NR. Beyond the obvious: targeting the SLC transportome and non-canonical drug transport mechanisms in cancer therapy. Invest New Drugs. 2025 Aug;43(4):1070-1085. doi: 10.1007/s10637-025-01577-w. Epub 2025 Aug 22.
PubMed 40847194
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of CB-839 and Capecitabine in Patients With Advanced Solid Tumors and Fluoropyrimidine Resistant PIK3CA Mutant Colorectal Cancer
- ClinicalTrials.gov ID
- NCT02861300
- Acronym / sponsor ID
- CASE1216
- Conditions
- Colorectal Cancer, Colon Cancer, Rectal Cancer, Solid Tumor
- Keywords
- CB-839, PIK3CA, capecitabine
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- David Bajor, MDUniversity, hospital or other
- Study start
- 12 Sep 2016 (actual)
- Primary completion
- 10 Jan 2023 (actual)
- Study completion
- 10 Jan 2023 (actual)
- First posted
- 10 Aug 2016 (estimated)
- Results
- Posted 19 Dec 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study has two portions. The main goal of the Phase I portion of this research study is to see what doses of CB-839 and capecitabine can safely be given to patients without having too many side effects. Other purposes of this research study will be to determine what side effects are seen with this combination of medicines. The Phase II portion of the study will test how many patients show shrinkage in their tumor with this combination of medicines and what changes occur inside the cancer cells and blood cells after treatment.
Detailed description
Phase I Primary Objective:
To determine the safety, tolerability and recommended phase II dose (RP2D) of combination CB-839 and capecitabine chemotherapy in patients with advanced solid tumors for whom there are no remaining treatment options or for whom single agent capecitabine is an acceptable therapy.
Phase II Primary Objective:
To determine the disease control rate of combination CB-839 and capecitabine chemotherapy in patients with metastatic PIK3CA mutant colorectal cancers who are refractory to fluoropyrimidine based therapy.
Phase I Secondary Objectives:
To determine the dose-limiting toxicities and maximum tolerated dose of combination therapy with CB-839 and capecitabine in patients with advanced solid tumors for whom there are no remaining treatment options or for whom single agent capecitabine is an acceptable therapy.
To determine the disease control rate as assessed by RECIST criteria of combination therapy with CB-839 and capecitabine in patients with advanced solid tumors for whom there are no remaining treatment options or for whom single agent capecitabine is an acceptable therapy.
Phase II Secondary Objectives:
To determine the progression free survival following treatment with CB-839 and capecitabine chemotherapy in patients with metastatic PIK3CA mutant colorectal cancer and are refractory to fluoropyrimidine therapy.
To determine the overall survival following treatment with CB-839 and capecitabine chemotherapy in patients who have metastatic PIK3CA mutant colorectal cancer and are refractory to fluoropyrimidine therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CB-839 + capecitabine | Experimental | Drug: CB-839, Drug: CapecitabinePatients will receive CB-839 orally twice daily for 21 days (continuous administration) and capecitabine orally twice daily for 14/21 days. In the phase I portion of the study, patients will receive escalating doses of CB-839 and capecitabine and will have day 15 blood samples drawn and archived for as needed assessment of CB-839 pharmacokinetics. In the phase II portion of the study, patients will receiving 800mg CB-839 and 1000mg/m^2 capecitabine as were determined to be safe doses during the phase I portion of the study. They will also undergo pre-treatment and post-treatment blood samples and tissue biopsies for evaluation of pharmacodynamic biomarkers. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (32 listed)
- Phase I
- Phase II
Key exclusion criteria (9 listed)
- Both Phase I and Phase II
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 |
|---|---|---|
| CB-839Patients will receive CB-839 orally twice daily during each cycle. Each cycle will be 21 days long. Disease assessment will occur after cycle 3. | Drug | CB-839 + capecitabine |
| CapecitabineAlso: Xelodacapecitabine will be given orally twice daily for 14-21 days of cycles. Each cycle will be 21 days long. Disease assessment will occur after cycle 3. | Drug | CB-839 + capecitabine |
Primary outcome
PHASE I: Recommended Dose for Phase II Study
Time frame: At least 21 days of treatment
The Phase I study has been designed to define the recommended phase II dose of CB-839 and capecitabine. A traditional 3+3 dose escalation design will be adopted. Nine to twenty-four patients are expected to be enrolled, depending on the number of dose escalations and assuming that a total of 6 patients will be treated at the final recommended phase II dose level. Patients who complete the first 21 day treatment cycle of CB-839 and capecitabine chemotherapy will be included in the analysis.
PHASE II: Progression-free Survival (PFS)
Time frame: 6 months
The number of participants that achieved PFS will be analyzed. Progression free survival (PFS) on combination CB-839 and capecitabine as determined by clinical assessment and RECIST criteria in patients with metastatic PIK3CA mutant colorectal cancer who are refractory to fluoropyrimidine based therapy. Progression free survival is defined as the time from randomization to documented progression or death without progression.
4 secondary outcomes
PHASE I: Proportion of Patient Who Respond to Treatment
Time frame: At least 21 days of treatment
PHASE I: Dose-limiting Toxicities
Time frame: Up to 18 months after beginning treatment
PHASE II: Number of Patients With Response to Treatment
Time frame: Up to 18 months after beginning treatment
PHASE II: Overall Survival
Time frame: Up to 18 months after beginning treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40847194Sridhar SK, Abass KS, Gowthami B, Naveen NR. Beyond the obvious: targeting the SLC transportome and non-canonical drug transport mechanisms in cancer therapy. Invest New Drugs. 2025 Aug;43(4):1070-1085. doi: 10.1007/s10637-025-01577-w. Epub 2025 Aug 22.
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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.
David Bajor, MD principal investigator
University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing CB-839 and Capecitabine in people with Colorectal Cancer and Colon Cancer, run by David Bajor, MD at 2 sites 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 32 inclusion and 9 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: finished, as of the sponsor's last update on 19 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 combined 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.
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?
Yes. Results are posted in the registry (first posted 19 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
PHASE I: Recommended Dose for Phase II Study (time frame: At least 21 days of treatment). The study lists 2 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 NCT02861300, 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 19 Dec 2024.