locally advanced or metastatic triple-negative breast cancer MedDRA version: 20.0 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 100000004864 MedDRA version: 21.1 Level: LLT Classification code 10072740 Term: Locally advanced breast cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: ALECSAT
Pharmaceutical Form: Solution for injection
Other descriptive name: ALECSAT
Trade Name: Carboplatin Fresenius Kabi
Pharmaceutical Form: Concentrate for solution for infusion
Oth
Sponsors
Henrik Ditzel
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Have signed informed consent to study participation. The patient may also provide consent for Future Biomedical Research (FBR). However, the patient may participate in the main study without participating in FBR. 2. Female patients aged 18 years and older 3. Have locally advanced inoperable breast which cannot be treated with curative intent OR have metastatic breast cancer. 4. Have a histologically or cytologically TNBC (defined by absence of HER2 and estrogen receptor (ER) expression on primary tumor) confirmed by local pathologist. Patients initially diagnosed with hormone receptor–positive and/or HER2-positive breast cancer must have confirmation of TNBC in a tumor biopsy obtained from a local recurrence or distant metastasis site. 5. Able and willing to provide a fresh tumor biopsy from a local recurrence or distant metastasis site. 6. Eligible for chemotherapy with carboplatin and gemcitabine. 7. WHO Performance status 0-1. 8. Has received no more than two prior regimens for locally advanced or metastatic breast cancer. Prior therapy with checkpoint inhibitors (anti–PD-1, anti–PD-L1, anti–PD-L2, or anti-CTLA-4) agent is allowed. 9. Have measurable disease based on RECIST 1.1 as determined by local radiology review. 10. Have life expectancy =3 months at time of enrollment. 11. Women of child-bearing potential must have a negative pregnancy test at screening and agree to use acceptable methods of contraception during the study. 12. Demonstrate adequate organ function, within 10 days prior to the start of study treatment, as defined: Hematological: Absolute neutrophil count (ANC) =1,500/µL, Lymphocyte count >0.3 x 109/L. Platelets =100,000/µL. Renal: Creatinine =1.5 × ULN OR measured creatinine clearance (GFR can also be used in place of creatinine or CrCl) =30 mL/min for patient with creatinine levels >1.5 × institutional ULN) Hepatic: Total bilirubin =1.5 ×ULN ASAT and ALT =2.5 × ULN (=5 × ULN for patients with liver metastases), Albumin =3.0 g/dL Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 15 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: 1. Previously treated with carboplatin / gemcitabine. 2. Prior therapy with ALECSAT or other cellular immunotherapies. 3. Is currently participating in a clinical study and receiving an investigational agent or has participated in a clinical study and received an investigational agent within 4 weeks prior to inclusion or during the trial. 4. Has not recovered (e.g., to =Grade 1 or to baseline) from AEs due to a previously administered therapy (alopecia excluded). Prior to inclusion, the patient must have recovered adequately from any toxicity and/or complications associated with any recent procedure. 5. Has an active autoimmune disease that has required systemic treatment in the past 2 years (e.g., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). 6. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to inclusion. 7. Positive blood tests for anti-HIV-1/2; HBsAg, anti-HBc, Anti-HCV or being positive in a Treponema Pallidum test (syphilis). 8. Patients who have been exposed to high risk contagious virus within a reasonable time prior to enrolment, e.g., by travelling in areas with known high risk of infection or known epidemics. This includes but is not limited to: ? West Nile virus (in season): Less than 28 days following return from affected area; less than 6 months following full recovery from known West Nile virus infection or symptoms suggestive of West Nile virus infection ? Dengue virus: Less than 28 days following return from affected area or cessation of symptoms (include high fever, joint pain, body pain, and/or rash) in case of confirmed Dengue virus infection; less than 6 months following full recovery from diagnosis of dengue hemorrhagic fever ? Zika virus: Less than 28 days following return from an affected area or after sexual contact with a male who has been diagnosed with Zika virus infection or with a male who travelled or lived in a Zika affected area during the three months prior to the sexual contact; less than 60 days following recovery of symptoms in case of confirmed Zika virus infection ? Ebola virus: Less than 60 days after return from an affected area; Patients previously diagnosed with Ebola virus should be excluded from the study 9. Patients from high incidence areas for Human T-Lymphotropic Virus type 1 (HTLV-1) or who has a parent from a high incidence area or who has had sexual contact with a partner from a high incidence area must be excluded unless tested negative for HTLV-1 10. Blood transfusion with whole blood or red blood cells within 48 hours prior to the donation of blood for ALECSAT production. 11. Has an active infection requiring systemic therapy. 12. Has a known additional malignancy that progressed or required active treatment within the last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, and in situ cervical cancer. 13. Patients with symptomatic brain metastases. Patients previously treated or untreated for these conditions that are asymptomatic in the absence of corticosteroid and anticonvulsant therapy for at least 6 weeks and size no more than 20 mm are allowed to enroll. Radiotherapy for brain metastasis must have been completed at least 6 weeks prior to start of study treatment. Brain metastasis must be stable with verification by imaging (e.g. brai
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary efficacy objective of this study is to evaluate progression free survival (PFS) based on Response Evaluation Criteria In Solid Tumors, version 1.1 (RECIST 1.1) criteria (1) in patients with histologically confirmed, inoperable locally advanced or metastatic TNBC treated with ALECSAT as an add-on therapy to carboplatin and gemcitabine.;Secondary Objective: 1) To evaluate the objective response rate (ORR) based on RECIST 1.1. 2) To evaluate the safety and tolerability of ALECSAT + gemcitabine/carboplatin. 3) To obtain activity data on duration of response (DOR) 4) To obtain activity data on disease control rate (DCR) of ALECSAT + gemcitabine/carboplatin according to RECIST v1.1. 5) To evaluate overall survival (OS) in all patients. 6) To compare ORR, DOR, and PFS based on modified RECIST 1.1 for immune-based therapeutics (iRECIST) with the same measures derived using RECIST 1.1, both as assessed by local radiologic review. 7) To identify predictive markers of response to ALECSAT (please see 8.2.4 for further details). 8) To evaluate the anti-tumor response of combining ALECSAT therapy with epigenetic drug or anti-PDL1 antibody therapy using PDX mouse models generated from the patient´s tumor tissue.;Primary end point(s): Primary Endpoint: progression-free survival (PFS) according to RECIST v1.1 ;Timepoint(s) of evaluation of this end point: Treatment phase:42 months maximum. ALECSAT loading and maintenance treatment combined with carboplatin/gemcitabine on days 1 and 8 every 3 weekly cycles until disease progression, death, unacceptable toxicity, investigator/patient decision or end-of treatment visit at 24 months following last patient first visit (LPFV). Follow up:Safety: 30 days after last administration of study drug. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Endpoints: Objective response rate (ORR), duration of response (DOR) and disease control rate (DCR) according to RECIST 1.1. Overall survival (OS). To evaluate tolerability and safety (CTCEA v 5.0): Adverse events from the first dose of study medication until 30 days after termination of study medication ;Timepoint(s) of evaluation of this end point: Treatment phase:42 months maximum. ALECSAT loading and maintenance treatment combined with carboplatin/gemcitabine on days 1 and 8 every 3 weekly cycles until disease progression, death, unacceptable toxicity, investigator/patient decision or end-of treatment visit at 24 months following last patient first visit (LPFV). Follow up:Safety: 30 days after last administration of study drug. | — |
Countries
Denmark
Contacts
Public ContactHenrik Ditzel
Onkologisk afdeling R, Odense Universitetshospital
Outcome results
None listed