Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer

• ClinicalTrials.gov Identifier: NCT02779855
• Recruitment Status: Active, not recruiting
• First Posted: May 20, 2016
• Last Update Posted: May 22, 2020
• Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Collaborator: Amgen
• Information provided by (Responsible Party): H. Lee Moffitt Cancer Center and Research Institute

Tracking Information

• First Submitted Date: May 19, 2016
• First Posted Date: May 20, 2016
• Last Update Posted Date: May 22, 2020
• Actual Study Start Date: May 2, 2017
• Estimated Primary Completion Date: August 31, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 19, 2016)

• Phase I: Maximum Tolerated Dose (MTD) / Recommended Phase II Dose (RP2D) [ Time Frame: Up to 6 months ]
  MTD/RP2D of talimogene laherparepvec administered with neoadjuvant paclitaxel- doxorubicin/cyclophosphamide chemotherapy.
• Phase II: Pathologic Complete Response Rate (pCR) [ Time Frame: Up to 36 months ]
  pCR following study treatment, defined as: Disappearance of histopathologic evidence of malignant cells in breast and axillary lymph nodes.

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided

Current Other Pre-specified Outcome Measures (submitted: May 19, 2016)

• Recurrence Free Survival Rate [ Time Frame: Up to 5 years follow-up ]
  Percentage of participants who are disease recurrence free at 5 year follow-up.
• Overall Survival (OS) Rate [ Time Frame: Up to 5 years follow-up ]
  Percentage of participants who are alive at 5 year follow-up.

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
• Official Title: A Phase 1/2 Study of Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Breast Cancer
• Ductal Carcinoma
• Invasive Breast Carcinoma
• Invasive Ductal Breast Carcinoma

Intervention

• Biological: Talimogene 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).
  Other Names:

  • IMLYGIC™
  • modified herpes simplex 1 virus
• Drug: Paclitaxel
  Paclitaxel chemotherapy infusion. The paclitaxel weekly dose is fixed at 80 mg/m^2.
  Other Name: Taxol®

Study Arms

Experimental: Talimogene laherparepvec + Chemotherapy

Talimogene laherparepvec with Neoadjuvant Paclitaxel Chemotherapy treatment administration on an outpatient basis. Phase I: Dose Escalation to Determine Maximum Tolerated Dose (MTD). Phase II: Treatment at MTD.

Interventions:

• Biological: Talimogene laherparepvec
• Drug: Paclitaxel

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: May 21, 2020): 50
• Original Estimated Enrollment (submitted: May 19, 2016): 46
• Estimated Study Completion Date: August 31, 2022
• Estimated Primary Completion Date: August 31, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02779855
• Other Study ID Numbers: MCC-18621
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
• Study Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Collaborators: Amgen

Investigators

• Principal Investigator: Hatem Soliman, M.D.; H. Lee Moffitt Cancer Center and Research Institute

• PRS Account: H. Lee Moffitt Cancer Center and Research Institute
• Verification Date: May 2020