Breast Cancer, Ductal Carcinoma, Invasive Breast Carcinoma, Invasive Ductal Breast Carcinoma
Conditions
Keywords
triple negative breast cancer (TNBC), estrogen receptor, progesterone receptor, invasive ductal carcinoma, breast cancer tumors
Brief summary
The purpose of this study is to determine if an oncolytic virus called Talimogene laherparepvec (a modified herpes simplex 1 virus that can specifically destroy cancer cells while leaving normal cells alone) injected directly into the tumor during chemotherapy prior to surgery can enhance the elimination of triple negative breast cancer tumors. The natural herpes simplex 1 virus typically causes cold sores around the mouth, but the talimogene laherparepvec version of the herpes virus has been changed to prevent it from reproducing in normal tissue. However, it can still attack and break open cancer tissue which is why it is used as a treatment for cancer. It is thought that this virus can also help recruit the participant's immune system to attack the cancer cells during their treatment and possibly destroy the tumor tissue more effectively than chemotherapy alone. This virus is already FDA approved to treat melanoma skin tumors, so investigators want to determine if this virus can achieve a similar benefit in women with triple negative breast tumors.
Interventions
BIOLOGICALTalimogene laherparepvec
Talimogene laherparepvec injection. Phase I: Dose escalation. Phase II: Treatment at Maximum Tolerated Dose (MTD) from Phase I. The MTD dose level is defined as the highest dose level with ≤1 out of 6 patients experiencing a dose limiting toxicity (DLT).
DRUGPaclitaxel
Paclitaxel chemotherapy infusion. The paclitaxel weekly dose is fixed at 80 mg/m\^2.
Sponsors
H. Lee Moffitt Cancer Center and Research Institute
Amgen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Must have histologically or cytologically confirmed clinical stage T2-3 N0-2 triple negative (estrogen receptor/progesterone receptor \<1% human epidermal growth factor receptor 2 (HER2) 0-1 by ImmunoHistoChemistry (IHC) or unamplified by fluorescence in situ hybridization (FISH)) invasive ductal carcinoma. * Must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>20 mm with conventional techniques or as \>10 mm with spiral CT scan. As well, participants must have primary tumor able to be visualized on ultrasound and amenable to direct injection. * No prior history of an invasive breast cancer * Adults ages 18-70 * Eastern Cooperative Oncology Group (ECOG) performance status 0-1 * Must have normal organ and marrow function as outlined in protocol * Sexually active women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation. * Ability to understand and the willingness to sign a written informed consent document
Exclusion criteria
* T4 tumors, known metastatic disease, recurrent disease, inflammatory breast cancer, multicentric disease, and/or synchronous bilateral breast cancer * A second active malignancy, exceptions are localized non-melanoma skin cancers or prior in situ carcinoma * Receiving any other investigational agents or are unable to be treated with doxorubicin, cyclophosphamide, and paclitaxel. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to talimogene laherparepvec or other agents used in the study * Known active or prior herpes simplex virus infections (HSV), prior complications from HSV infections such as encephalitis, or require systemic antiviral therapy at the time of study enrollment * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, known active hepatitis B/C infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Women who are pregnant or nursing * Immunocompromised patients may be at increased risk of herpetic infections when treated with talimogene laherparepvec. Therefore, HIV-positive patients, patients with acquired or congenital immunodeficiency conditions, those on chronic systemic immunosuppressants (requiring \> 10 mg of prednisone or equivalent/day), Those with active autoimmune disease are excluded from the study. * Have received any live vaccine therapies used for the prevention of infectious disease within 28 days prior to enrollment and during treatment period. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed. However, intranasal influenza vaccines (eg, Flu - Mist®) are live attenuated vaccines, and are not allowed.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase I: Maximum Tolerated Dose (MTD) / Recommended Phase II Dose (RP2D) | Up to 6 months | MTD/RP2D of talimogene laherparepvec administered with neoadjuvant paclitaxel- doxorubicin/cyclophosphamide chemotherapy. |
| Phase II: Percentage of Participants With Pathologic Complete Response Rate (pCR) | Up to 36 months | Perceptage of participants with pCR following study treatment, defined as: Disappearance of histopathologic evidence of malignant cells in breast and axillary lymph nodes. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORHatem Soliman, M.D.
H. Lee Moffitt Cancer Center and Research Institute
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Phase 1 Dose Level 1 Talimogene laherparepvec with Neoadjuvant Paclitaxel Chemotherapy treatment administration on an outpatient basis. Phase I Dose Level 1: 10\^6 PFU (plaque forming units) for all five injections
Paclitaxel: Paclitaxel chemotherapy infusion. The paclitaxel weekly dose is fixed at 80 mg/m\^2. | 3 |
| Phase 1 Dose Level 2 Talimogene laherparepvec with Neoadjuvant Paclitaxel Chemotherapy treatment administration on an outpatient basis. Phase I Dose Level 2: 10\^6 PFU (plaque forming units) 1st injection, followed by 10\^8 for remaining injections.
Paclitaxel: Paclitaxel chemotherapy infusion. The paclitaxel weekly dose is fixed at 80 mg/m\^2. | 6 |
| Phase 2 Phase II: Treatment at Maximum Tolerated Dose (MTD) from Phase I. The MTD dose level is defined as the highest dose level with ≤1 out of 6 patients experiencing a dose limiting toxicity (DLT).
Talimogene laherparepvec: Talimogene laherparepvec injection. Phase II: treatment at MTD
Paclitaxel: Paclitaxel chemotherapy infusion. The paclitaxel weekly dose is fixed at 80 mg/m\^2. | 40 |
| Total | 49 |
Baseline characteristics
| Characteristic | Phase 1 Dose Level 1 | Phase 1 Dose Level 2 | Phase 2 | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 6 Participants | 38 Participants | 47 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 6 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 4 Participants | 33 Participants | 38 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 5 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 4 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) White | 2 Participants | 3 Participants | 27 Participants | 32 Participants |
| Region of Enrollment United States | 3 participants | 6 participants | 40 participants | 49 participants |
| Sex: Female, Male Female | 3 Participants | 6 Participants | 40 Participants | 49 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 4 / 6 | 1 / 40 |
| other Total, other adverse events | 3 / 3 | 6 / 6 | 39 / 40 |
| serious Total, serious adverse events | 1 / 3 | 4 / 6 | 7 / 40 |
Outcome results
Primary
Phase II: Percentage of Participants With Pathologic Complete Response Rate (pCR)
Perceptage of participants with pCR following study treatment, defined as: Disappearance of histopathologic evidence of malignant cells in breast and axillary lymph nodes.
Time frame: Up to 36 months
Population: All patients evaluable for response per protocol
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Talimogene Laherparepvec + Chemotherapy | Phase II: Percentage of Participants With Pathologic Complete Response Rate (pCR) | 66.7 percentage of participants |
| Phase 1 Dose Level 2 | Phase II: Percentage of Participants With Pathologic Complete Response Rate (pCR) | 50 percentage of participants |
| Phase 2 | Phase II: Percentage of Participants With Pathologic Complete Response Rate (pCR) | 43.24 percentage of participants |
Primary
Phase I: Maximum Tolerated Dose (MTD) / Recommended Phase II Dose (RP2D)
MTD/RP2D of talimogene laherparepvec administered with neoadjuvant paclitaxel- doxorubicin/cyclophosphamide chemotherapy.
Time frame: Up to 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Talimogene Laherparepvec + Chemotherapy | Phase I: Maximum Tolerated Dose (MTD) / Recommended Phase II Dose (RP2D) | 100 million plaque forming units per mL |
Other Pre-specified
Overall Survival (OS) Rate
Percentage of participants who are alive at 5 year follow-up.
Time frame: Up to 5 years follow-up
Other Pre-specified
Recurrence Free Survival Rate
Percentage of participants who are disease recurrence free at 5 year follow-up.
Time frame: Up to 5 years follow-up