Clinical Trials /

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

NCT03487666

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: OXEL: Pilot Study of Immune Checkpoint or Capecitabine or Combination Therapy as Adjuvant Therapy for TNBC With Residual Disease
  • 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

Clinical Trial IDs

  • ORG STUDY ID: 2017-1535
  • NCT ID: NCT03487666

Conditions

  • Triple Negative Breast Cancer

Interventions

DrugSynonymsArms
NivolumabOpdivoArm A
CapecitabineXelodaArm B

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Arm AExperimentalNivolumab 360 mg iv q3weeks for x 6 cycles
  • Nivolumab
Arm BActive ComparatorCapecitabine 1250mg/m2 bid D1-D14 q3 weeks x 6 cycles
  • Capecitabine
Arm CExperimentalNivolumab 360mg iv q3weeks + Capecitabine 1250mg/m2 bid D1-D14 q3 weeks x 6 cycles
  • Nivolumab
  • Capecitabine

Eligibility Criteria

        Inclusion criteria:

          1. 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

          2. Residual disease of 1.0 cm at least of the primary tumor and/or node positive disease
             (at least ypN1)

          3. 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.

          4. Recovery of all toxicities from previous therapies to at least grade 1, except
             alopecia and ≤ grade 2 neuropathy which are allowed.

          5. 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

          6. ECOG PS 0-2

          7. 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.

          8. At the time of registration (randomization), patients must have the following
             laboratory results (obtained within 28 days prior to registration):

               1. A serum TSH prior to registration to obtain a baseline value.

               2. 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.

               3. 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.

               4. 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.

               5. 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.

          9. Signed ICF

         10. Age ≥18

        Exclusion criteria:

          1. Stage IV disease

          2. Receipt of adjuvant chemotherapy

          3. 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

          4. Previous exposure to capecitabine, fluorouracil or immunotherapy with anti-PD1,
             anti-PDL1, anti-CTLA4 or similar drugs.

          5. Active autoimmune disease that has required systemic treatment in the past 2 years;
             replacement therapy is not considered a form of systemic therapy

          6. 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.

          7. History of (non-infectious) pneumonitis that required steroids or evidence of active
             pneumonia

          8. Uncontrolled disease

          9. Chronic use of systemic steroids

         10. Live vaccine within 30 days prior to registration.

         11. Incapacity to provide consent or to follow clinical trial procedures

         12. 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Immune activation measured by changes in the peripheral immunoscore (PIS) at week 6
Time Frame:6 weeks
Safety Issue:
Description:Quantification of immune activation measured by changes of PIS from baseline to week 6 in each arm.

Secondary Outcome Measures

Measure:Immune activation measured by changes of PIS at week 12
Time Frame:12 weeks
Safety Issue:
Description:Quantification of immune activation measured by changes of PIS from baseline to week 12 in each arm.
Measure:Grade 3 and 4 toxicities according to the National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.0 [NCI CTCAE v4.03]
Time Frame:18 weeks + 30 days after last dose received
Safety Issue:
Description:Quantification of grade 3 and 4 toxicities according to the National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.0 [NCI CTCAE v4.03]
Measure:Distant recurrence free survival (DRFS) and Overall Survival
Time Frame:3 years
Safety Issue:
Description:To determine association between changes in PIS from baseline to week 6 and week 12 and clinical outcome variables (DRFS and OS at 3 years). After end of study visit, clinical follow up or telephone communication every 3 months (DRFS and OS at 3 years). Distant recurrence free survival (DRFS) is defined by time from study enrollment to date of first invasive distant disease recurrence, second invasive primary cancer (breast or not), or death due to any cause.
Measure:Immune activation in the tumor by IHC
Time Frame:18 weeks
Safety Issue:
Description:Quantification of immune activation by IHC
Measure:Immune activation in the tumor by flow cytometry
Time Frame:18 weeks
Safety Issue:
Description:Quantification of immune activation by flow cytometry
Measure:Immune activation in the tumor by ELISA
Time Frame:18 weeks
Safety Issue:
Description:Quantification of immune activation by ELISA
Measure:Intracellular cytokine staining and CD8+ T-cell clonal expansion
Time Frame:18 weeks
Safety Issue:
Description:Quantification of antigen-specific responses by intracellular cytokine staining and CD8+ T-cell clonal expansion
Measure:Circulating tumor DNA
Time Frame:12 weeks
Safety Issue:
Description:Quantification of ct-DNA at different time points

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Georgetown University

Trial Keywords

  • Triple Negative Breast Cancer
  • Nivolumab
  • Capecitabine

Last Updated