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.
Recruiting
Phase 1/Phase 2
| Drug | Synonyms | Arms |
|---|---|---|
| P10s-PADRE with MONTANIDE™ ISA 51 VG + Doxorubicin + Cyclophosphamide + Paclitaxel | P10s-PADRE/ MONTANIDE™ ISA 51 VG with standard neoadjuvant chemotherapy | Chemo+Vaccine Arm |
| Doxorubicin + Cyclophosphamide + Paclitaxel | Standard neoadjuvant chemotherapy | Control Arm |
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 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.
| Name | Type | Description | Interventions |
|---|---|---|---|
| Control Arm | Active Comparator | 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. |
|
| Chemo+Vaccine Arm | Experimental | 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. |
|
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | Female |
| Healthy Volunteers: | No |
| Measure: | Safety/tolerability |
| Time Frame: | At the time of definitive surgery (4-8 weeks after chemo); between Week 20 and Week 23 |
| Safety Issue: | |
| Description: | Monitor the safety and tolerability of the investigational product, P10s-PADRE in MONTANIDETM ISA 51 VG, when it is administered in combination with SoC Neoadjuvant chemotherapy. |
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | University of Arkansas |
July 28, 2021
