OXEL: Immune Checkpoint or Capecitabine or Combination Therapy as Adjuvant Therapy for TNBC With Residual Disease

NCT03487666 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 2017-1535
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Triple Negative Breast Cancer

Keywords

Triple Negative Breast Cancer; Nivolumab; Capecitabine

Outcome Measures

Primary Outcomes (1)

• 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.

  6 weeks

Secondary Outcomes (4)

• Percent Change of Peripheral Immuno Score (PIS) at Week 12

  12 weeks

• Grade 3 and 4 Adverse Events

  From date of consent until 100 days after the last dose of study treatment, approximately up to 11 months

• Invasive Disease Free Survival (DRFS)

  2 years

• Circulating Tumor DNA

  6 weeks and 12 weeks

Study Arms (3)

Arm A

EXPERIMENTAL

Nivolumab 360 mg iv q3weeks for x 6 cycles

Drug: Nivolumab

Arm B

ACTIVE COMPARATOR

Capecitabine 1250mg/m2 bid D1-D14 q3 weeks x 6 cycles

Drug: Capecitabine

Arm C

EXPERIMENTAL

Nivolumab 360mg iv q3weeks + Capecitabine 1250mg/m2 bid D1-D14 q3 weeks x 6 cycles

Drug: Nivolumab; Drug: Capecitabine

Interventions

Nivolumab DRUG

Nivolumab is a human programmed death receptor-1 (PD-1) antibody currently approved in different diseases.

Also known as: Opdivo

Arm A; Arm C

Capecitabine DRUG

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

Also known as: Xeloda

Arm B; Arm C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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):

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Georgetown University: lead
• Bristol-Myers Squibb: collaborator

Study Sites (4)

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

MedStar Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Related Publications (1)

• 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.

  PMID: 40274284 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

Nivolumab; Capecitabine

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Candace Mainor, MD
• Organization: Georgetown University

Candace.Mainor@gunet.georgetown.edu

202-444-2223

Study Officials

• Candace Mainor, MD

  MedStar Georgetown University Hospital

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2018
• First Posted: April 4, 2018
• Study Start: May 21, 2018
• Primary Completion: November 3, 2021
• Study Completion: May 2, 2024
• Last Updated: December 3, 2024
• Results First Posted: December 3, 2024

Record last verified: 2024-11

Locations

US (4)