Triple Negative Breast CancerPhase 2NCT03487666
OXEL: Immune Checkpoint or Capecitabine or Combination Therapy as Adjuvant Therapy for TNBC With Residual Disease
A Phase 2 study testing Nivolumab and Capecitabine in people with Triple Negative Breast Cancer, run by Georgetown University at 4 sites in United States.
Trial summary
This pilot study will provide preliminary data regarding the role of PIS in predicting the benefit of immune checkpoint inhibition with or without chemotherapy for high risk patients with TNBC and residual disease after effective neoadjuvant chemotherapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Triple Negative Breast Cancer
- What is being tested?
- Nivolumab and Capecitabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 4 sitesUnited States
- Study dates
- 21 May 2018to 2 May 2024
- Phase
- Phase 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Biopsy proven TNBC:
- ER- and PR- defined as ≤5% cells stain positive
- HER2 negativity defined as:
- IHC 0, 1+ without in situ hybridization (ISH) HER2/neu chromosome 17 ratio OR
- IHC 2+ and ISH HER2/neu chromosome 17 ratio non-amplified with ratio less than 2.0 and if reported average HER2 copy number < 6 signals/cells
- Residual disease of 1.0 cm at least of the primary tumor and/or node positive disease (at least ypN1)
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- Patients must have completed neoadjuvant chemotherapy; patients must NOT have received capecitabine as part of their neoadjuvant therapy regimen. Acceptable preoperative regimens include an anthracycline or a taxane, or both. Participants who received preoperative therapy as part of a clinical trial may enroll. Participants may not have received adjuvant chemotherapy after s urgery prior to randomization. . Carboplatin-containing neoadjuvant chemotherapy is also allowed). Patients who cannot complete all planned neoadjuvant treatment cycles for any reason are considered high risk and therefore are eligible for the study if they have residual disease.
- Recovery of all toxicities from previous therapies to at least grade 1, except alopecia and ≤ grade 2 neuropathy which are allowed.
- Must have completed definitive resection of primary tumor and have no evidence of unresected or metastatic disease at the time of study entry
- Negative margins for both invasive and ductal carcinoma in situ (DCIS) are desirable, however patients with positive margins may enroll if the treatment team believes no further surgery is possible and patient has received radiotherapy; patients with margins positive for lobular carcinoma in situ (LCIS) are eligible
- Either mastectomy or breast conserving surgery (including lumpectomy or partial mastectomy) is acceptable
- Sentinel node biopsy post neoadjuvant chemotherapy (i.e. at the time of definitive surgery) is allowed; axillary dissection is encouraged in patients with lymph node involvement, but is not mandatory
- ECOG PS 0-2
- Patients must not be planning to receive concomitantly other biologic therapy, hormonal therapy, other chemotherapy, surgery or other anti-cancer therapy except radiation therapy while receiving treatment on this protocol.
- At the time of registration (randomization), patients must have the following laboratory results (obtained within 28 days prior to registration):
- A serum TSH prior to registration to obtain a baseline value.
- Patients must have adequate bone marrow function as evidenced by all of the following:
- ANC ≥ 1,500 microliter (mcL);
- Platelets ≥ 100,000/mcL;
- Hemoglobin ≥ 9 g/dL.
- Patients must have adequate hepatic function as evidenced by the following:
- Total bilirubin ≤ 1.5 x institutional upper limit of normal (IULN) (except Gilbert's Syndrome, who must have a total bilirubin < 3.0 mg/dL), and
- SGOT (AST) or SGPT (ALT) and alkaline phosphatase ≤ 2.5 x IULN.
- Patients must have adequate renal function as evidenced by ONE of the following:
- Serum creatinine ≤ IULN OR
- Measured or calculated creatinine clearance ≥ 60 mL/min.
- Women of childbearing potential must have a negative urine or serum pregnancy test within 28 days prior to registration and within 24h prior to the start of nivolumab. In addition, women of childbearing potential must agree to have a pregnancy test every 4 weeks while on nivolumab.
- Signed ICF
- Age ≥18
Who cannot join
- Stage IV disease
- Receipt of adjuvant chemotherapy
- Diagnosis of other invasive cancer except for adequately treated cervix cancer or skin cancer, or more than 5 years since other diagnosis of invasive cancer without current evidence of disease
- Previous exposure to capecitabine, fluorouracil or immunotherapy with anti-PD1, anti-PDL1, anti-CTLA4 or similar drugs.
- Active autoimmune disease that has required systemic treatment in the past 2 years; replacement therapy is not considered a form of systemic therapy
- TB, active hepatitis B, active hepatitis C or other active infection. Patients who have completed curative therapy for HCV are eligible. Patients with known HIV infection are eligible if they meet each of the following 3 criteria: CD4 counts ≥ 350 mm3; serum HIV viral load of < 25,000 IU/ml and treated on a stable antiretroviral regimen.
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- History of (non-infectious) pneumonitis that required steroids or evidence of active pneumonia
- Uncontrolled disease
- Chronic use of systemic steroids
- Live vaccine within 30 days prior to registration.
- Incapacity to provide consent or to follow clinical trial procedures
- Pregnancy, lactation, or planning to be pregnant
- Patients with microsatellite unstable tumors will not be excluded as immunotherapy as adjuvant therapy is not standard for these patients but we will prospective collect this data.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
University of Chicago
Chicago, Illinois, 60637
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, 07601
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007
MedStar Washington Hospital Center
Washington D.C., District of Columbia, 20010
About this study
Official title: OXEL: A Pilot Study of Immune Checkpoint or Capecitabine or Combination Therapy as Adjuvant Therapy for Triple Negative Breast Cancer With Residual Disease Following Neoadjuvant Chemotherapy
This pilot study will provide preliminary data regarding the role of PIS in predicting the benefit of immune checkpoint inhibition with or without chemotherapy for high risk patients with TNBC and residual disease after effective neoadjuvant chemotherapy.
- Conditions
- Triple Negative Breast Cancer
- Being tested
- Nivolumab, Capecitabine
- Keywords
- Triple Negative Breast Cancer, Nivolumab, Capecitabine
- Medical subject headings
- Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabDrug
Also called Opdivo
Nivolumab is a human programmed death receptor-1 (PD-1) antibody currently approved in different diseases.
CapecitabineDrug
Also called Xeloda
Capecitabine was selected for Arm B given the recent results from CREATE-X trial and the increasing use by the community (feasibility). Importantly, available data from other scenarios indicates that capecitabine does not have immunosuppressive effects
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | Nivolumab 360 mg iv q3weeks for x 6 cycles Receives: Drug: Nivolumab |
| Arm B | Active comparator | Capecitabine 1250mg/m2 bid D1-D14 q3 weeks x 6 cycles Receives: Drug: Capecitabine |
| Arm C | Experimental | Nivolumab 360mg iv q3weeks + Capecitabine 1250mg/m2 bid D1-D14 q3 weeks x 6 cycles Receives: Drug: Nivolumab; Drug: Capecitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change in the Peripheral Immunoscore (PIS) at Week 6
PIS were developed using methods previously described (Farsaci, B. et al. Cancer Immunol. Res. 2016), based on tertile distribution of frequencies and ratios of peripheral immune cell subsets in patients prior to therapy. Immune subsets were calculated as a % of PBMC and sorted by frequency. Points were assigned to each subset in a given patient based on tertile distribution. For subsets with an expected positive effect on anti-tumor immunity zero (0) points were assigned to the low bin, one (1) point for the middle bin, and two (2) points if in the high bin. For subsets with an expected negative effect on anti-tumor immunity zero (0) points were assigned to the high bin, one (1) point for the middle bin, and two (2) points if in the low bin. The peripheral immunoscore for a given patient was the sum of points assigned to the individual PBMC subsets that were included within the immunoscore. Positive change means enhanced and negative change means reduced immune function.
Measured: 6 weeks
Secondary outcomes (4)
Percent Change of Peripheral Immuno Score (PIS) at Week 12
PISs were developed using methods previously described (Farsaci, B. et al. Cancer Immunol. Res. 2016), based on tertile distribution of frequencies and ratios of peripheral immune cell subsets in patients prior to therapy. Immune subsets were calculated as a % of PBMC and sorted by frequency. Points were assigned to each subset in a given patient based on tertile distribution. For subsets with an expected positive effect on anti-tumor immunity zero (0) points were assigned to the low bin, one (1) point for the middle bin, and two (2) points if in the high bin. For subsets with an expected negative effect on anti-tumor immunity zero (0) points were assigned to the high bin, one (1) point for the middle bin, and two (2) points if in the low bin. The peripheral immunoscore for a given patient was the sum of points assigned to the individual PBMC subsets that were included within the immunoscore. Positivie change mean enhanced and negative change means reduced immune function.
Measured: 12 weeks
Grade 3 and 4 Adverse Events
The number of grade 3 and 4 adverse events as assessed clinically by an investigator, according to the National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.0 [NCI CTCAE v4.03]. Grade 4 adverse events were associated with worse outcomes.
Measured: From date of consent until 100 days after the last dose of study treatment, approximately up to 11 months
Invasive Disease Free Survival (DRFS)
iDFS was defined as the time from date of randomization to the date of first invasive disease recurrence, second invasive primary cancer (breast or not), or death from any cause.
Measured: 2 years
Circulating Tumor DNA
Out of the patients with available ct-DNA samples at baseline, week 6 and week 12, the proportion of patients with detectable ct-DNA at the same timepoints.
Measured: 6 weeks and 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2018
- Study start21 May 2018
- Primary completion3 Nov 2021
- Study completion2 May 2024
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 Triple Negative Breast CancerStudies of the same condition, open and under way.
- More trials run by Georgetown UniversityThe sponsor's other registered studies.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Georgetown University
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Candace Mainor, MD, Study chair, MedStar Georgetown University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03487666
- Sponsor's protocol ID
- 2017-1535
- Status last verified
- Nov 2024
- First submitted
- 20 Mar 2018
- Last updated
- 3 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Toney NJ, Lynch MT, Lynce F, Mainor C, Isaacs C, Schlom J, Donahue RN. Serum analytes as predictors of disease recurrence and the duration of invasive disease-free survival in patients with triple negative breast cancer enrolled in the OXEL trial treated with immunotherapy, chemotherapy, or chemoimmunotherapy. J Immunother Cancer. 2025 Apr 23;13(4):e011379. doi: 10.1136/jitc-2024-011379.
PubMed 40274284
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- OXEL: A Pilot Study of Immune Checkpoint or Capecitabine or Combination Therapy as Adjuvant Therapy for Triple Negative Breast Cancer With Residual Disease Following Neoadjuvant Chemotherapy
- ClinicalTrials.gov ID
- NCT03487666
- Acronym / sponsor ID
- 2017-1535
- Conditions
- Triple Negative Breast Cancer
- Keywords
- Triple Negative Breast Cancer, Nivolumab, Capecitabine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Georgetown UniversityUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- 21 May 2018 (actual)
- Primary completion
- 3 Nov 2021 (actual)
- Study completion
- 2 May 2024 (actual)
- First posted
- 4 Apr 2018 (actual)
- Results
- Posted 3 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 pilot study will provide preliminary data regarding the role of PIS in predicting the benefit of immune checkpoint inhibition with or without chemotherapy for high risk patients with TNBC and residual disease after effective neoadjuvant chemotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm A | Experimental | Drug: NivolumabNivolumab 360 mg iv q3weeks for x 6 cycles |
| Arm B | Active comparator | Drug: CapecitabineCapecitabine 1250mg/m2 bid D1-D14 q3 weeks x 6 cycles |
| Arm C | Experimental | Drug: Nivolumab, Drug: CapecitabineNivolumab 360mg iv q3weeks + Capecitabine 1250mg/m2 bid D1-D14 q3 weeks x 6 cycles |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (29 listed)
- Biopsy proven TNBC:
- Residual disease of 1.0 cm at least of the primary tumor and/or node positive disease (at least ypN1)
- Patients must have completed neoadjuvant chemotherapy; patients must NOT have received capecitabine as part of their neoadjuvant therapy regimen. Acceptable preoperative regimens include an anthracycline or a taxane, or both. Participants who received preoperative therapy as part of a clinical trial may enroll. Participants may not have received adjuvant chemotherapy after s urgery prior to randomization. . Carboplatin-containing neoadjuvant chemotherapy is also allowed). Patients who cannot complete all planned neoadjuvant treatment cycles for any reason are considered high risk and therefore are eligible for the study if they have residual disease.
- Recovery of all toxicities from previous therapies to at least grade 1, except alopecia and ≤ grade 2 neuropathy which are allowed.
- Must have completed definitive resection of primary tumor and have no evidence of unresected or metastatic disease at the time of study entry
Key exclusion criteria (13 listed)
- Stage IV disease
- Receipt of adjuvant chemotherapy
- Diagnosis of other invasive cancer except for adequately treated cervix cancer or skin cancer, or more than 5 years since other diagnosis of invasive cancer without current evidence of disease
- Previous exposure to capecitabine, fluorouracil or immunotherapy with anti-PD1, anti-PDL1, anti-CTLA4 or similar drugs.
- Active autoimmune disease that has required systemic treatment in the past 2 years; replacement therapy is not considered a form of systemic therapy
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 |
|---|---|---|
| NivolumabAlso: OpdivoNivolumab is a human programmed death receptor-1 (PD-1) antibody currently approved in different diseases. | Drug | Arm A, Arm C |
| CapecitabineAlso: XelodaCapecitabine was selected for Arm B given the recent results from CREATE-X trial and the increasing use by the community (feasibility). Importantly, available data from other scenarios indicates that capecitabine does not have immunosuppressive effects | Drug | Arm B, Arm C |
Primary outcome
Percent Change in the Peripheral Immunoscore (PIS) at Week 6
Time frame: 6 weeks
PIS were developed using methods previously described (Farsaci, B. et al. Cancer Immunol. Res. 2016), based on tertile distribution of frequencies and ratios of peripheral immune cell subsets in patients prior to therapy. Immune subsets were calculated as a % of PBMC and sorted by frequency. Points were assigned to each subset in a given patient based on tertile distribution. For subsets with an expected positive effect on anti-tumor immunity zero (0) points were assigned to the low bin, one (1) point for the middle bin, and two (2) points if in the high bin. For subsets with an expected negative effect on anti-tumor immunity zero (0) points were assigned to the high bin, one (1) point for the middle bin, and two (2) points if in the low bin. The peripheral immunoscore for a given patient was the sum of points assigned to the individual PBMC subsets that were included within the immunoscore. Positive change means enhanced and negative change means reduced immune function.
4 secondary outcomes
Percent Change of Peripheral Immuno Score (PIS) at Week 12
Time frame: 12 weeks
Grade 3 and 4 Adverse Events
Time frame: From date of consent until 100 days after the last dose of study treatment, approximately up to 11 months
Invasive Disease Free Survival (DRFS)
Time frame: 2 years
Circulating Tumor DNA
Time frame: 6 weeks and 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40274284Toney NJ, Lynch MT, Lynce F, Mainor C, Isaacs C, Schlom J, Donahue RN. Serum analytes as predictors of disease recurrence and the duration of invasive disease-free survival in patients with triple negative breast cancer enrolled in the OXEL trial treated with immunotherapy, chemotherapy, or chemoimmunotherapy. J Immunother Cancer. 2025 Apr 23;13(4):e011379. doi: 10.1136/jitc-2024-011379.
- Related InfoLink provided by the sponsor.
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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.
Candace Mainor, MD study chair
MedStar Georgetown University Hospital
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nivolumab and Capecitabine in people with Triple Negative Breast Cancer, run by Georgetown University at 4 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 29 inclusion and 13 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 3 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 4 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 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?
Yes. Results are posted in the registry (first posted 3 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?
Percent Change in the Peripheral Immunoscore (PIS) at Week 6 (time frame: 6 weeks). 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 NCT03487666, 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 3 Dec 2024.