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Nadunolimab in Combination With Gemcitabine Plus Carboplatin in Patients With Advanced Triple Negative Breast Cancer. (TRIFOUR)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05181462
Recruitment Status : Recruiting
First Posted : January 6, 2022
Last Update Posted : March 3, 2022
Sponsor:
Collaborator:
Spanish Breast Cancer Research Group
Information provided by (Responsible Party):
Cantargia AB

Brief Summary:

Triple negative breast cancer (TNBC) represents approximately 15% of all breast cancers (BC) worldwide. The term triple negative means that tumor growth is not stimulated by the hormones estrogen and progesterone, nor by the HER2 protein, so unlike other types of BC, TNBC, which is an aggressive form of BC, does not have specific effective therapies available being the least common form of BC and the most difficult to treat.

Advanced or metastatic TNBC is treated with combinations of platinum-based chemotherapy with taxanes or gemcitabine with a 5-year survival rate of 12%. Recent studies have shown that TNBC expresses Interleukin 1 Receptor Accessory Protein (IL1RAP) at higher levels than other forms of BC.

Nadunolimab is a fully humanized monoclonal antibody that blocks the signals that occur within the cell produced by IL1RAP protein, thereby impairing the cancer cells' ability to secrete tumor stimulating substances, in turn reducing the tumor, inflammation and tumor progression. On the other hand, it is an antibody designed to activate the immune system to fight cancer cells.

This clinical trial is divided into two phases, phase Ib in which it is expected to include up to 18 patients and phase II in which it is expected to include 98 patients. The main purpose of phase Ib is to ensure that the combination of nadunolimab plus chemotherapy (gemcitabine plus carboplatin) is safe and determine the highest dose of nadunolimab that can be given safely without causing serious side effects. If the pre-specified objectives in this part are achieved, the trial will be expanded to a randomized phase II, to evaluate the efficacy of the combination of nadunolimab plus gemcitabine plus carboplatin, compared to a control group that will receive gemcitabine plus carboplatin only.


Condition or disease Intervention/treatment Phase
Triple Negative Breast Cancer Drug: Carboplatin Drug: Gemcitabine Drug: Nadunolimab Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 116 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Phase Ib: Single-arm (dose-escalation 3+3 design).

  • Carboplatin Area Under the Curve (AUC) 2 mg/mL/min intravenous (IV) on days 1 and 8, every 3-week cycles.
  • Gemcitabine 1000 mg/m2 IV on days 1 and 8, every 3-week cycles.
  • Nadunolimab escalation (Dose Level (DL) -1: 0.5 mg/Kg, DL 1: 1 mg/kg, DL 2: 2.5 mg/kg), DL 3: 5 mg/kg IV on days 1 and 8, every 3-week cycles.

Phase II: Randomized 1:1, non-comparative, open-label.

Patients randomized to arm A will receive:

  • Carboplatin AUC 2 mg/mL/min IV on days 1 and 8, every 3-week cycles.
  • Gemcitabine 1000 mg/m2 IV on days 1 and 8, every 3-week cycles.
  • Nadunolimab Recommended Phase II Dose (RP2D) mg/kg IV on days 1 and 8, every 3-week cycles.

Patients randomized to arm B will receive:

  • Carboplatin AUC 2 mg/mL/min IV on days 1 and 8, every 3-week cycles.
  • Gemcitabine 1000 mg/m2 IV on days 1 and 8, every 3-week cycles.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Non-comparative Open-label Phase 1b/2 Study of Nadunolimab in Combination With Gemcitabine Plus Carboplatin in Patients With Advanced Triple Negative Breast Cancer. "TRIFOUR Study"
Actual Study Start Date : January 11, 2022
Estimated Primary Completion Date : August 2024
Estimated Study Completion Date : August 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Phase Ib: Single-arm (dose-escalation 3+3 design).
  • Carboplatin Area Under the Curve (AUC) 2 mg/mL/min intravenous (IV) on days 1 and 8, every 3-week cycles.
  • Gemcitabine 1000 mg/m2 IV on days 1 and 8, every 3-week cycles.
  • Nadunolimab escalation (DL -1: 0.5 mg/Kg, DL 1: 1 mg/kg, DL 2: 2.5 mg/kg), DL 3: 5 mg/kg IV on days 1 and 8, every 3-week cycles.
Drug: Carboplatin
Carboplatin Area Under the Curve (AUC) 2 mg/mL/min intravenous (IV) on days 1 and 8, every 3-week cycles

Drug: Gemcitabine
Gemcitabine 1000 mg/m2 IV on days 1 and 8, every 3-week cycles

Drug: Nadunolimab
Nadunolimab escalation (DL -1: 0.5 mg/Kg, DL 1: 1 mg/kg, DL 2: 2.5 mg/kg), DL 3: 5 mg/kg IV on days 1 and 8, every 3-week cycles.
Other Name: CAN04

Experimental: Phase II: Randomized 1:1, non-comparative, open-label.Patients randomized to arm A
  • Carboplatin AUC 2 mg/mL/min IV on days 1 and 8, every 3-week cycles.
  • Gemcitabine 1000 mg/m2 IV on days 1 and 8, every 3-week cycles.
  • Nadunolimab Recommended Phase II Dose (RP2D) mg/kg IV on days 1 and 8, every 3-week cycles
Drug: Carboplatin
Carboplatin Area Under the Curve (AUC) 2 mg/mL/min intravenous (IV) on days 1 and 8, every 3-week cycles

Drug: Gemcitabine
Gemcitabine 1000 mg/m2 IV on days 1 and 8, every 3-week cycles

Drug: Nadunolimab
Nadunolimab escalation (DL -1: 0.5 mg/Kg, DL 1: 1 mg/kg, DL 2: 2.5 mg/kg), DL 3: 5 mg/kg IV on days 1 and 8, every 3-week cycles.
Other Name: CAN04

Active Comparator: Phase II: Randomized 1:1, non-comparative, open-label.Patients randomized to arm B
  • Carboplatin AUC 2 mg/mL/min IV on days 1 and 8, every 3-week cycles.
  • Gemcitabine 1000 mg/m2 IV on days 1 and 8, every 3-week cycles.
Drug: Carboplatin
Carboplatin Area Under the Curve (AUC) 2 mg/mL/min intravenous (IV) on days 1 and 8, every 3-week cycles

Drug: Gemcitabine
Gemcitabine 1000 mg/m2 IV on days 1 and 8, every 3-week cycles




Primary Outcome Measures :
  1. Incidence rate of Dose Limiting Toxicity (DLT) within the first cycle of nadunolimab in combination with gemcitabine plus carboplatin [ Time Frame: At the end of Cycle 1 (each cycle is 21 days) ]

    DLT is defined according to the NCI-CTCAE version 5.0 as any of the following events considered by investigator to be related to investigational treatment:

    1. Grade (G) 5 Treatment Emergent AE
    2. G ≥ 3 neutropenia + fever and/or infection (single temp. > 38.3°C or sustained temp. ≥ 38°C >1 hour)
    3. G 4 neutropenia > 7 days
    4. G 4 thrombocytopenia > 3 days
    5. G ≥ 3 thrombocytopenia > 7 days or accompanied by G 2 bleeding or platelet transfusion
    6. Delay in the initiation of Cycle 2 > 7 days from the calculated start date due to a lack of adequate recovery of treatment-related hematological or non-hematological toxicity
    7. G ≥ 3 AE with permanent discontinuation of any of the study drugs
    8. Elevations of bilirubin and transaminases meeting Hy's Law criteria
    9. G 4 laboratory abnormalities discussed with the Medical Coordinators, Sponsor and GEICAM
    10. G ≥ 3 non-hematological toxicity
    11. G 2 toxicity considered a dose limiting

  2. Objective Response Rate (ORR) [ Time Frame: Through study completion, an average of 58 months ]

    Tumor response is assessed according to Response Evaluation Criteria for Solid Tumors (RECIST) version 1.1 as per investigators' assessment.

    ORR is defined as the rate of Complete Response (CR) plus Partial Response (PR) according to RECIST version 1.1, out of the patients who receive at least one dose of treatment and have measurable disease. These results will be calibrated against the ORR in the control arm.



Secondary Outcome Measures :
  1. Clinical Benefit Rate (CBR) [ Time Frame: Through study completion, an average of 58 months ]
    CBR is defined as the rate of a Complete Response (CR) plus Partial Response (PR) plus Stable Disease (SD) lasting ≥ 24 weeks, according to RECIST v1.1 and as per investigator's assessment out of enrolled patients. n. Per RECIST, CR is defined as the disappearance of all target lesions; PR is defined as an >=30% decrease in the sum of the longest diameter of target lesions; SD is defined as a failure to meet criteria for CR or PR in the absence of progressive disease

  2. Disease Control Rate (DCR) [ Time Frame: Through study completion, an average of 58 months ]
    DCR is defined as the rate of CR, PR plus SD of any duration, according to RECIST v1.1 and as per investigator's assessment out of enrolled patients.

  3. Duration of Response (DoR) [ Time Frame: Through study completion, an average of 58 months ]
    DoR assessed according to RECIST v1.1, is defined as the time from the date of first documentation of overall response (CR or PR) to the date of first documented progressive disease (PD), or death from any cause, whichever occurs first. PD is defined using RECIST, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

  4. Progression-Free Survival (PFS) [ Time Frame: Through study completion, an average of 58 months ]
    PFS according to RECIST v1.1 as per the investigator's assessment. It is defined as the time from the date of enrolment to the date of PD or death from any cause, whichever occurs first.

  5. Proportion of patients free of PD at 6 and 12 months [ Time Frame: Up to 12 months ]
    PD is defined using RECIST, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions within 6 and 12 months.

  6. PFS rate at 6 and 12 months [ Time Frame: Up to 12 months ]
    PFS according to RECIST v1.1 as per the investigator's assessment. It is defined as the time from the date of enrolment to the date of PD or death from any cause, whichever occurs first at 6 and 12 months

  7. Overall Survival (OS) [ Time Frame: Through study completion, an average of 58 months ]
    OS is defined as the time from the date of enrolment to the date of death from any cause.

  8. Proportion of patients alive at 12 and 18 months [ Time Frame: Up to 12 months ]
    Proportion of patients alive at 12 and 18 months; on the basis of the median duration of OS observed.

  9. Immune Overall Response Rate (iORR) [ Time Frame: Through study completion, an average of 58 months ]
    Response parameters per Guidelines for Response Criteria for Use in Trials Testing Immunotherapeutics (iRECIST) criteria in patients who receive treatment beyond PD by RECIST 1.1 Tumor response is assessed using iRECIST. iORR is defined as the percentage of patients with a Immune Complete Response (iCR) or Immune Partial Response (iPR) out of the patients from the efficacy population. Per iRECIST, iCR is defined as the disappearance of all measurable and non-measurable lesions, and lymph nodes must decrease to < 10 mm in short axis; iPR is defined as an >=30% decrease in total measured tumor burden relative to baseline; Immune Overall Response (iOR) = iCR + iPR.

  10. Immune Clinical Benefit Rate (iCBR) [ Time Frame: Through study completion, an average of 58 months ]
    Response parameters per iRECIST criteria in patients who receive treatment beyond PD by RECIST 1.1 Tumor response is assessed using iRECIST. iCBR is defined as the rate of a Immune Complete Response (iCR) plus Immune Partial Response (iPR) plus Immune Stable Disease (iSD) lasting ≥ 24 weeks iCR is defined as the disappearance of all target lesions; iPR is defined as an >=30% decrease in the sum of the longest diameter of target lesions; iSD is defined as a failure to meet criteria for iCR or iPR in the absence of progressive disease

  11. Immune Disease Control Rate (iDCR) [ Time Frame: Through study completion, an average of 58 months ]
    Response parameters per iRECIST criteria in patients who receive treatment beyond PD by RECIST 1.1 iDCR is defined as the rate of iCR, iPR plus iSD of any duration

  12. Immune Progression Free Survival (iPFS) [ Time Frame: Through study completion, an average of 58 months ]
    Response parameters per iRECIST criteria in patients who receive treatment beyond PD by RECIST 1.1 iPFS is defined as the time from the date of enrolment to the date of immuno Progressive Disease (iPD) or death from any cause, whichever occurs first.

  13. The Number of Participants Who Experienced Adverse Events (AE) [ Time Frame: Through study completion, an average of 58 months ]
    It will be assessed by the frequency, severity and nature of AEs, serious adverse event (SAE), changes in vital signs and standard clinical and laboratory tests (haematology, serum chemistry, and urine). The severity of AEs will be graded by the NCI CTCAE version 5.0 and the AE terms will be coded by the current version of the Medical Dictionary for Regulatory Activities (MedDRA).

  14. Change from baseline (CFB) by Quality of Life (QoL) [ Time Frame: At 12,18 and 24 months ]

    CFB in the global health status (GHS) score and each scale of the EORTC quality of life questionnaire (QLQ) -C30 questionnaire.

    Patient reported outcomes of health-related quality of life will be assessed using the EORTC QLQ-C30 questionnaire and analyzed on the QoL population.

    Published scoring manuals and guidelines will be used to generate scale scores and handle missing data. Descriptive statistics for actual values will be tabulated at each scheduled time point.

    CFB will be presented at each scheduled time point for the GHS score and each of the functionals and symptoms scales from the EORTC QLQ-C30 questionnaires.

    Longitudinal analysis of scores will be performed using linear mixed models.


  15. Time to deterioration (TTD) by Quality of Life (QoL) [ Time Frame: At 12,18 and 24 months ]

    CFB in the global health status (GHS) score and each scale of the EORTC QLQ-C30 questionnaire.

    Patient reported outcomes of health-related quality of life will be assessed using the EORTC QLQ-C30 questionnaire and analyzed on the QoL population.

    Published scoring manuals and guidelines will be used to generate scale scores and handle missing data. Descriptive statistics for actual values will be tabulated at each scheduled time point.

    TTD will be assessed using the Kaplan-Meier method. The median event time and 95% CI for the median will be estimated if reached. TTD will be censored at the date of the last QoL assessment prior to the start of a new therapy.


  16. Incidence of Tolerability [ Time Frame: Through study completion, an average of 58 months ]
    It will be assessed by incidence of different type of dose modifications, discontinuations due to AEs, number of administered cycles, etc.

  17. Exposure levels of nadunolimab when administered in combination with gemcitabine plus carboplatin (Pharmacokinetics) [ Time Frame: Days 1 and 8 from all cycles and post-treatment visit, an average of 58 months ]
    Blood samples for nadunolimab serum concentration analysis will be collected prior to each nadunolimab infusion and 1 hour after the end of each nadunolimab infusion on Day 1 and on Day 8 (all cycles), and at post-treatment visit (30 (±3) days after the last dose of study treatment.

  18. Anti-drug antibodies (ADAs) against nadunolimab (Immunogenicity) [ Time Frame: Days 1 and 8 from all cycles and post-treatment visit, an average of 58 months ]

    The formation of ADAs against nadunolimab will be assessed in blood samples collected prior to nadunolimab administration on Day 1 of each cycle and post-treatment visit.

    Immunogenicity will be evaluated by determination of the presence of ADAs as measured in serum by a tiered testing approach involving an initial screening assay, confirmation, and titration of confirmed positive samples. Samples will be banked so that further characterisation of the effect of ADAs upon nadunolimab binding to its target antigen may be undertaken.

    Characterisation of banked samples will include assessment of neutralising antibodies for samples that have been confirmed positive for ADA




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria: Patients are eligible to be enrolled in the study only if they meet all of the following criteria:

  1. The patient has signed and dated the informed consent form (ICF) and it has been obtained before conducting any specific procedure for the study.
  2. Female or male BC patients of ≥ 18 years of age.
  3. Permission to access archived tumor tissue sample (either from primary breast tumor or a metastatic lesion, preferably the most recent one) for biomarker analysis. Not having archived tissue is not a reason to exclude the patient from enrollment.
  4. Paired tumor biopsies, pre-treatment and on-treatment, for pharmacodynamic analysis are not compulsory and will be obtained as per investigator judgement and patient decision. However, patients and investigators are encouraged to obtain them if the patient has easily accessible disease like skin or superficial lymph nodes. Ideally, the same lesion (always in the same organ) should be biopsied before treatment and on treatment whenever possible. It is allowed to use archived biopsies as pre-treatment samples, obtained after ending the previous systemic treatment).
  5. The lesion accessible for biopsy may not be the only target lesion and should not be located in a previously irradiated field (unless this index lesion has PD ≥ 20% post-radiation).
  6. Histologically confirmed TNBC that is either locally recurrent, inoperable and cannot be treated with curative intent or is metastatic:

    1. Documented Hormone Receptor (HR) negative BC based on local laboratory determination on the most recent tumor biopsy. HR negative defined as < 1% positive cells by immunohistochemistry (IHC) for estrogen receptor (ER) and progesterone receptor (PgR).
    2. Documented Human Epidermal Growth Factor Receptor 2 (HER2) negative BC based on local laboratory determination on the most recent tumor biopsy. HER2 negative tumor is determined according to recommendations of the applicable American Society of Clinical Oncology (ASCO)/ College of American Pathologists (CAP) guidelines available.
    3. Patients are eligible for the study irrespectively of BRCA1/2 mutational status. It is not required to have the analysis performed before the study inclusion.
  7. Patients should be eligible to receive gemcitabine and carboplatin as the following line of therapy. No more than 1 previous line of systemic therapy for the advanced disease is allowed:

    1. Those patients with PD during or within 6 months after completing the (neo)adjuvant treatment are allowed to be included in the study and are considered for second-line group of patients.
    2. Prior therapy with immuno-checkpoint inhibitors (ICIs) either in the metastatic setting (as first-line therapy) or in the (neo)adjuvant setting is allowed.
    3. Previous treatment with platinum-derived agents in early-stage setting is allowed if the platinum-free interval is at least of 12 months.
    4. Prior therapy with PARP inhibitors is allowed.
  8. Documented progressive disease (i.e. biopsy sample, pathology or imaging report) from the last treatment.
  9. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1.
  10. Patients must have at least one measurable lesion that can be accurately assessed at baseline and is suitable for repeated assessment by CT scan, MRI, plan X-ray or physical examination. Clinical lesions will only be considered measurable when they are superficial and ≥ 10mm in diameter as assessed using callipers (e.g. skin nodules). Patients with bone-only disease must have a lytic or mixed (lytic + blastic) lesion, which has not been previously irradiated and can be accurately assessed by CT scan/MRI according to RECIST version 1.1 (with a component of soft tissue mass).
  11. Adequate organ and bone marrow function defined as follows:

    e. Absolute Neutrophil Count (ANC) ≥ 1.500/mm3 (1.5x109/L), without previous Granulocyte Colony-Stimulating Factor (G-CSF) within 2 weeks prior to the study treatment.

    f. Platelets ≥ 100.000/mm3 (100x109/L), without previous transfusion within 2 weeks prior to the study treatment.

    g. Hemoglobin ≥ 9 g/dL (90 g/L), without previous transfusion within 28 days before starting with the study treatment.

    h. Serum creatinine ≤ 1.5 x Upper Limit of Normal (ULN) or estimated creatinine clearance ≥ 60 mL/min as calculated using the Cockcroft-Gault formula.

    i. Total serum bilirubin ≤ 1.5 x ULN (≤ 3.0 x ULN if Gilbert´s disease). j. Aspartate aminotransferase (AST) and/or Alanine aminotransferase (ALT) ≤ 3.0 x ULN (≤ 5.0 x ULN if liver metastases present).

    k. Alkaline phosphatase ≤ 2.5 x ULN (≤ 5.0 x ULN if bone or liver metastases present).

  12. Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to NCI CTCAE v5.0 Grade ≤ 1 (except alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion). In case of immune-related toxicities, adequately resolved to Grade 1 or non-persistent Grade 2 AEs with the recommended measures by the current guidelines.
  13. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
  14. Negative serum pregnancy test for premenopausal women, and for women who have experienced menopause onset < 12 month prior to first dose of therapy..

    • For premenopausal women: agreement to remain abstinent or use single or combined non-hormonal contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 7 months after the last dose of study treatment.
    • For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and to refrain from donating sperm during the same period, as defined below with female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 6 months after the last dose of carboplatin/gemcitabine to avoid exposing the embryo. Due to the possibility of irreversible infertility with carboplatin/gemcitabine, men receiving these chemotherapies should consult with their doctor regarding conservation of sperm prior to treatment initiation.

Abstinence is only acceptable if it is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of contraception.

Examples of non-hormonal contraceptive methods with a failure rate of < 1% per year include tubal ligation, male sterilization, and certain intrauterine devices. Alternatively, two methods (e.g., two barrier methods such as a condom and a cervical cap) may be combined to achieve a failure rate of < 1% per year. Barrier methods must always be supplemented with the use of a spermicide.

Exclusion Criteria:Patients will be excluded from the study if they meet any of the following criteria:

  1. Patient has received extended field radiotherapy ≤ 4 weeks before the start of treatment (≤ 2 weeks for limited field radiation for palliation), and who has not recovered to ≤ Grade 1, according to NCI CTCAE v5.0, from related AEs of such therapy (except for alopecia).
  2. Treatment with systemic anticancer treatments, investigational products, or major surgery within 4 weeks before the first dose of study drug or 5 half-lives, whichever is shorter. Patients should have recovered from previous treatment toxicity to ≤ Grade 1 (except alopecia and peripheral neuropathy).
  3. No prior treatment with an anthracycline and a taxane unless contraindicated or not considered the most suitable treatment option (e.g. in the de novo metastatic setting) according to physician's opinion.
  4. Significant cardiovascular disease, such as New York Heart Association (NYHA) cardiac disease (Class II or greater), myocardial infarction, or cerebrovascular accident within 3 months prior to randomisation, unstable arrhythmias, or unstable angina. Patients with a known left ventricular ejection fraction (LVEF) < 50% will be excluded.
  5. Patients with known coronary artery disease or congestive heart failure (CHF) not meeting the above criteria, must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate.
  6. Presence of an abnormal ECG that is clinically significant in the investigator's opinion, including complete left bundle branch block, second or third-degree heart block, or QT interval corrected using Fridericia's formula (QTcF) > 480 ms demonstrated by at least two consecutive ECGs.
  7. Patients with uncontrolled brain metastases; however, patients who have been previously treated with surgery, whole-brain radiation, and/or stereotactic radiosurgery and are considered controlled (with ≤ 10 mg/day of prednisone or equivalent) at the time of receiving the first dose of nadunolimab are allowed. For asymptomatic patients, screening brain imaging is not required.
  8. Spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for > 2 weeks prior to enrolment.
  9. Severe (Grade 3) infection requiring oral or IV antibiotics within 4 weeks prior to enrolment, including but not limited to hospitalization for complications of infection, bacteremia, or pneumonia. Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
  10. Patients testing positive for human immunodeficiency virus (HIV) are NOT excluded from this study, but HIV-positive patients must meet all the following criteria:

    1. Have CD4+ T-cell (CD4+) counts ≥ 350 350 cells/µL.
    2. Have not had an opportunistic infection within the past 12 months. Patients on prophylactic antimicrobials can be included in the study.
    3. Should be on stable antiretroviral therapy for at least 4 weeks.
    4. Have an HIV viral load less than 400 copies/mL prior to enrolment.
  11. Negative hepatitis B surface antigen (HBsAg) test at screening. Negative total hepatitis B core antibody (HBcAb) test at screening, or positive HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening. Patients who have a positive HBcAb test should have negative viral load.
  12. Negative hepatitis C virus (HCV) antibody test at screening or positive HCV antibody test followed by a negative HCV RNA test at screening. The HCV RNA test will be performed only for patients who have a positive HCV antibody test.
  13. Pregnant or lactating or intending to become pregnant during or within 6 months after the last dose of study treatment.
  14. Known hypersensitivity or allergy to any component of the nadunolimab, carboplatin or gemcitabine drug formulations, and known hypersensitivity to platinum-containing compounds.
  15. Patients who receive a live vaccination, etanercept, or other Tumor necrosis factor (TNF)-alpha inhibitors just prior to participation in this study (within 28 days of first study drug administration).
  16. Patients with a history of autoimmune disease requiring systemic immunosuppressive therapy (daily prednisone equivalent doses > 10 mg/day). Patients with autoimmune diseases and without systemic therapies are allowed.
  17. Diagnosis of any other malignancy within 5 years prior to randomization, except for adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of any origin or stage I colorectal.
  18. Patients with a history of slowly progressive dyspnea and non-productive cough or disorders such as sarcoidosis, silicosis, idiopathic pulmonary fibrosis, hypersensitivity pneumonitis lung or multiple allergies.
  19. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications.
  20. Polymerase chain reaction (PCR) positive or antigen test positive for coronavirus disease 2019 (COVID-19). Patients who had previously symptomatic COVID-19 infection should have recovered to Grade ≤ 1 or baseline.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05181462


Contacts
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Contact: CANTARGIA AB +46 46 2756260 clinicaltrials@cantargia.com

Locations
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Spain
Hospital Universitario Virgen De La Victoria Recruiting
Málaga, Andalucía, Spain, 29010
Hospital Universitario Virgen Del Rocío Not yet recruiting
Sevilla, Andalucía, Spain, 41013
Hospital Universitario Central de Asturias Recruiting
Oviedo, Asturias, Spain, 33011
Hospital del Mar Not yet recruiting
Barcelona, Cataluña, Spain, 08003
Hospital Clinic de Barcelona Recruiting
Barcelona, Cataluña, Spain, 08036
ICO Institut Catalá d'Oncologia de L´Hospitalet Recruiting
Hospitalet de Llobregat, Barcelona, Cataluña, Spain, 08908
Fundación Instituto Valenciano de Oncología Recruiting
Valencia, Comunidad Valenciana, Spain, 46009
Complejo Hospitalario Universitario A Coruña Recruiting
A Coruña, Galicia, Spain, 15006
Hospital Universitario Gregorio Marañón Recruiting
Madrid, Spain, 28007
Clínica Universidad de Navarra Recruiting
Madrid, Spain, 28027
Hospital Clínico San Carlos Not yet recruiting
Madrid, Spain, 28040
Hospital Universitario 12 de Octubre Recruiting
Madrid, Spain, 28041
Sponsors and Collaborators
Cantargia AB
Spanish Breast Cancer Research Group
Investigators
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Study Director: Chief Investigator Hospital General Universitario Gregorio
Study Director: Chief Investigator Clínica Universitaria de Navarra
Study Director: Chief Investigator Instituto de Investigación Sanitaria (IIS) Biodonostia - OSI
Study Director: Chief Medical Officer Cantargia AB
Additional Information:
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Responsible Party: Cantargia AB
ClinicalTrials.gov Identifier: NCT05181462    
Other Study ID Numbers: CAN04CLIN005
2021-003402-46 ( EudraCT Number )
First Posted: January 6, 2022    Key Record Dates
Last Update Posted: March 3, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The Study Protocol and the Statistical Analysis Plan (SAP) will be shared on the ClinicalTrials.gov web site. Also, results will be publish on congresses and manuscripts in scientific journal.
Supporting Materials: Study Protocol
Time Frame: When results will be analyzed following the Statistical Analysis Plan (SAP).
Access Criteria: The results will be published. Every efforts Will be made to have open-access manuscripts.
URL: https://cantargia.com/

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Cantargia AB:
Unresectable locally advanced
Metastatic triple negative breast cancer
Nadunolimab
Additional relevant MeSH terms:
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Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Gemcitabine
Carboplatin
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs