A Combined Phase i/II Efficacy Study of a Carbohydrate Mimotope-based Vaccine With MONTANIDE™ ISA 51 VG STERILE Combined With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 2
- 主要终点
- Safety and Tolerability Adverse Events
研究概览
简要总结
The purpose of this study is to evaluate a new investigational cancer vaccine, P10s-PADRE in combination with standard neoadjuvant chemotherapy and surgery in patients with clinical stage I, II or III triple negative breast cancer (TNBC). This study will compare the vaccine plus standard neoadjuvant chemotherapy and surgery to standard neoadjuvant chemotherapy and surgery alone.
详细描述
The purpose of this study is to evaluate an investigational agent, P10s-PADRE, a peptide mimotope-based vaccine, in combination with standard neoadjuvant chemotherapy in patients with clinical stage I, II or III estrogen-receptor (ER) negative, progesterone receptor (PR) negative and HER2-negative (= triple negative - TN) breast cancer. P10s-PADRE will be administered with MONTANIDE™ ISA 51 VG as adjuvant. Human breast cancers that express Tumor Associated Carbohydrate Antigens (TACAs) can be immunogenic, and enhancing the anti-TACA antibodies and immune effector function already present may augment the cytotoxic effects of standard therapies.
A randomized two-arm, open-label, multi-center phase I/II trial is designed with the goal being to evaluate the efficacy of combining vaccination of the P10s-PADRE formulation with neoadjuvant chemotherapy. Patients will be randomly assigned in a 2:1 ratio to standard chemotherapy plus P10s-PADRE or to standard chemotherapy alone. Efficacy will be based on the rate of pathologic Complete Response (pCR) observed among TN breast-cancer patients treated with the combination as compared with the group of patients who receive standard chemotherapy alone.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Females of all races with biopsy-proven clinical stage I, II, or III TNBC (ER-negative, PR-negative and HER2-negative) who will undergo SoC neoadjuvant treatment
- •Age 18 years and older
- •ECOG Performance Status 0 or 1
- •White blood cell (WBC) count ≥ 3,000/mm3 within 3 weeks prior to registration
- •Platelet count ≥ 100,000/mm3 within 3 weeks prior to registration
- •Bilirubin ≤ 2 x institutional upper limit (IUL) of normal obtained within 3 weeks prior to registration
- •Serum glutamic-oxaloacetic transaminase (SGOT) or aspartate aminotransferase test (AST) ≤ 2 x IUL of normal obtained within 3 weeks prior to registration
- •Serum glutamic-pyruvic transaminase (SGPT) or alanine aminotransferase test (ALT) ≤ 2 x IUL of normal obtained within 3 weeks prior to registration
- •Serum creatinine ≤ 1.8 mg/dl obtained within 3 weeks prior to registration
- •Must sign an informed consent document approved by the UAMS IRB
排除标准
- •ER-positive, PR-positive, HER2-positive, inflammatory, metastatic, stage IV or recurrent breast cancer.
- •Active infection requiring treatment with antibiotics.
- •Existing diagnosis or history of organic brain syndrome that might preclude participation in the full protocol.
- •Existing diagnosis or history of significant impairment of basal cognitive function that might preclude participation in the full protocol.
- •Other current malignancies. Subjects with prior history at any time of any in situ cancer, including lobular carcinoma of the breast in situ, cervical cancer in situ, atypical melanocytic hyperplasia or Clark I melanoma in situ or basal or squamous skin cancer are eligible, provided they are disease-free at the time of registration. Subjects with other malignancies are eligible if they have been continuously disease free for ≥ 5 years prior to the time of registration.
- •Active autoimmune disorders or conditions of immunosuppression; Existing diagnosis or history of autoimmune disorders or conditions of immunosuppression that have been in remission for less than 6 months.
- •Treatment with corticosteroids, including oral steroids (i.e. prednisone, dexamethasone [except when used as an antiemetic in SoC therapy]), continuous use of topical steroid creams or ointments or any steroid-containing inhalers. Subjects who discontinue the use of these classes of medication for at least 6 weeks prior to registration are eligible if, in the judgment of the treating physician, the subject is not likely to require these classes of drugs during the treatment period. Replacement doses of steroids for subjects with adrenal insufficiency are allowed.
- •Pregnancy or breastfeeding (due to the unknown effects of peptide/mimotope vaccines on a fetus or infant). Women of childbearing potential must have a negative urine pregnancy test within 72 hours prior to starting week 1 and must be counseled to use an accepted and effective method of contraception (including abstinence) while on treatment and for a period of 18 months after completing or discontinuing treatment. Accepted methods of contraception include oral contraceptives, barrier methods, IUDs, and abstinence.
- •Any other significant medical or psychiatric conditions, which, in the opinion of the enrolling investigator, may interfere with consent or compliance of the treatment regimen.
- •Enrollment in any other clinical trial using investigational drug products or devices prior to first post-surgery study lab (Week 46 visit). Concurrent enrollment in observational studies is allowed.
研究组 & 干预措施
Chemotherapy Only Arm
Subjects randomized to the control arm will receive SoC neoadjuvant chemotherapy starting on week 1. Doxorubicin and cyclophosphamide (AC) will be administered concurrently every two weeks for four cycles with pegfilgrastim (or equivalent growth factor) on day 2 of each AC cycle, followed by paclitaxel weekly x 12 weeks.
干预措施: Doxorubicin (Drug)
Chemotherapy Only Arm
Subjects randomized to the control arm will receive SoC neoadjuvant chemotherapy starting on week 1. Doxorubicin and cyclophosphamide (AC) will be administered concurrently every two weeks for four cycles with pegfilgrastim (or equivalent growth factor) on day 2 of each AC cycle, followed by paclitaxel weekly x 12 weeks.
干预措施: Cyclophosphamide (Drug)
Chemotherapy Only Arm
Subjects randomized to the control arm will receive SoC neoadjuvant chemotherapy starting on week 1. Doxorubicin and cyclophosphamide (AC) will be administered concurrently every two weeks for four cycles with pegfilgrastim (or equivalent growth factor) on day 2 of each AC cycle, followed by paclitaxel weekly x 12 weeks.
干预措施: Paclitaxel (Drug)
Chemo+Vaccine Arm
Subjects randomized to the chemo+vaccine arm will be immunized with P10s-PADRE in MONTANIDE™ ISA 51 VG a total of three times. The vaccine will be administered on weeks 1, 2 and 3 prior to chemotherapy. Then, they will start their SoC neoadjuvant chemotherapy on week 4. Doxorubicin and cyclophosphamide (AC) will be administered concurrently every two weeks for four cycles with pegfilgrastim (or equivalent growth factor) on day 2 of each AC cycle, followed by paclitaxel weekly x 12 weeks.
干预措施: P10s-PADRE with MONTANIDE™ ISA 51 VG (Biological)
Chemo+Vaccine Arm
Subjects randomized to the chemo+vaccine arm will be immunized with P10s-PADRE in MONTANIDE™ ISA 51 VG a total of three times. The vaccine will be administered on weeks 1, 2 and 3 prior to chemotherapy. Then, they will start their SoC neoadjuvant chemotherapy on week 4. Doxorubicin and cyclophosphamide (AC) will be administered concurrently every two weeks for four cycles with pegfilgrastim (or equivalent growth factor) on day 2 of each AC cycle, followed by paclitaxel weekly x 12 weeks.
干预措施: Doxorubicin (Drug)
Chemo+Vaccine Arm
Subjects randomized to the chemo+vaccine arm will be immunized with P10s-PADRE in MONTANIDE™ ISA 51 VG a total of three times. The vaccine will be administered on weeks 1, 2 and 3 prior to chemotherapy. Then, they will start their SoC neoadjuvant chemotherapy on week 4. Doxorubicin and cyclophosphamide (AC) will be administered concurrently every two weeks for four cycles with pegfilgrastim (or equivalent growth factor) on day 2 of each AC cycle, followed by paclitaxel weekly x 12 weeks.
干预措施: Cyclophosphamide (Drug)
Chemo+Vaccine Arm
Subjects randomized to the chemo+vaccine arm will be immunized with P10s-PADRE in MONTANIDE™ ISA 51 VG a total of three times. The vaccine will be administered on weeks 1, 2 and 3 prior to chemotherapy. Then, they will start their SoC neoadjuvant chemotherapy on week 4. Doxorubicin and cyclophosphamide (AC) will be administered concurrently every two weeks for four cycles with pegfilgrastim (or equivalent growth factor) on day 2 of each AC cycle, followed by paclitaxel weekly x 12 weeks.
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Safety and Tolerability Adverse Events
时间窗: From the start of treatment to the time of definitive surgery (4-8 weeks after chemo); from Week 0 to Week 20-23
A Safety/Tolerability Event is defined as the occurrence of one of the following: * A Serious Adverse Event, OR * A non-Serious Adverse Event of Grade = 3, 4, or 5, OR * A non-Serious Adverse Event of Grade = 2 whose Relationship to P10s-PADRE Vaccine was classified as Definite, Probable, or Possible
Pathologic Complete Response (pCR)
时间窗: During and/or Immediately After Surgery
A tumor-response call of either ypT0N0 or ypTisN0 determined through surgical staging after neoadjuvant therapy. The staging system used to determine the tumor-response call is the AJCC Staging System described in a 2014 FDA Guidance for Industry. • A tumor-response call of "pyT0N0" is also equated with pCR in the published literature.
Pathological Node Status: Number of Positive Lymph Nodes
时间窗: Surgery
Number of positive lymph nodes found out of dissected lymph nodes
Pathological Node Status: Number of Dissected Lymph Nodes
时间窗: Surgery
Number of dissected lymph nodes at surgery for study participants
Tumor Response
时间窗: Surgery
Participants had their tumors surgically removed and pathologically staged using the AJCC Staging criteria. The main method of pathologic staging for breast cancer is the TNM system which stands for (Tumor size, lymph Node status and Metastases). "yp" prior to TN means the tissue was staged after neoadjuvant therapy. The larger the number after "T" means the larger the size, and the larger the number after "N" means the number of affected nearby lymph nodes. Therefore, tumor gradings with T3Nx are worse than those with T0Nx. The two categories "pyT0N0" and "ypT0N0" are both considered to be synonymous with pCR in the published literature.
Pathological Tumor Size
时间窗: Surgery
Tumor size at surgery/pathology report
次要结局
- Frequencies of T Cells - CD3+/CD4+(Weeks 1, 7, 10, 15, 18, 23, and 46)
- Frequencies of T Cells - CD3+/CD8+(Weeks 1, 7, 10, 15, 18, 23, and 46)
- Fold Increase in P10s-MAP-Reactive Immunoglobulin Titers(Weeks 7, 10, 15, 18, 23, 46, and 70)
- Frequencies of Cells - CD69+/CD3+(Weeks 1, 7, 10, 15, 18, 23, 46, and 70)
- Activation Profiles of T Cells - CD69 on CD3+(Weeks 1, 7, 10, 15, 18, 23, 46, 70)
- Frequencies of NK Cells - CD16(Week 1, 7, 10, 15, 18, 23, 46, 70)
- Frequencies of NK Cells - NKG2D(Weeks 1, 7, 10, 15, 18, 23, 46, and 70)
- Activation Profiles of NK Cells: CD69(Weeks 1, 7, 10, 15, 18, 23, 46, and 70)
- Activation Profiles of NK Cells: NKp46(Weeks 1, 7, 10, 15, 18, 23, 46, and 70)
- Activation Profiles of NK Cells: NKG2D(Weeks 1, 7, 10, 15, 18, 23, 46, and 70)
- Activation Profiles of NK Cells: CD16(Weeks 1, 7, 10, 15, 18, 23, 46, and 70)
- Frequencies of NK Cells - CD69(Weeks 1, 7, 10, 15, 18, 23, 46, and 70)
- Frequencies of NK Cells - NKp46(Weeks 1, 7, 10, 15, 18, 23, 46, and 70)
- Frequencies of Circulating Regulatory T Cells (Tregs)(Weeks 1, 7, 10, 15, 18, 23, 46, and 70)