Clinical Trials /

Talimogene Laherparepvec in Treating Patients With Recurrent Breast Cancer That Cannot Be Removed by Surgery

NCT02658812

Description:

This phase II trial studies how well talimogene laherparepvec works in treating patients with breast cancer that has come back and cannot be removed by surgery. Biological therapies, such as talimogene laherparepvec, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop cancer cells from growing.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Talimogene Laherparepvec (T-VEC) for Breast Cancer Local Recurrence
  • Official Title: A Phase II Study Using Talimogene Laherparepvec as a Single Agent for Inflammatory Breast Cancer (IBC) or Non-IBC Patients With Inoperable Local Recurrence

Clinical Trial IDs

  • ORG STUDY ID: 2014-0034
  • SECONDARY ID: NCI-2016-00199
  • NCT ID: NCT02658812

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
Talimogene Laherparepvec (T-VEC)T-VEC, OncoVEX GM-CSFTalimogene Laherparepvec (T-VEC)

Purpose

The goal of this clinical research study is to learn if talimogene laherparepvec can help to control recurrent breast cancer. The safety of this drug will also be studied.

Detailed Description

      Study Drug Administration:

      Participant will receive the study drug in cycles. Cycle 1 will be 3 weeks and every cycle
      after that will be 2 weeks.

      If participant is found to be eligible to take part in this study, they will receive
      talimogene laherparepvec as an injection into the tumor on Day 1 of each cycle. If the
      doctor thinks it is in participant's best interest, they may also receive injections into
      areas of the skin to which the disease has spread.

      Study Visits:

      On Day 1 of Cycles 1 and 2:

        -  Participant will have a physical exam.

        -  Blood (about 2 tablespoons) will be drawn for routine tests, if this has not been done
           in the last 7 days.

        -  At Cycle 2, photographs will be taken of lesions on participant's chest.

      On Day 1 of Cycle 5:

        -  Participant will have a physical exam.

        -  Blood (about 7 tablespoons) will be drawn for routine tests, to check the immune
           system, and for tumor marker testing.

        -  Participant will have a CT or PET/CT scan to check the status of the disease.
           Participant may have a bone scan, if PET/CT is not available.

        -  Photographs will be taken of any lesions on participant's chest.

        -  If the doctor thinks it is needed, participant will have a core biopsy to check the
           immune system and to check the status of the disease.

      On Day 1 of Cycle 7 and then every odd numbered cycle after that (Cycles 9, 11, 13, and so
      on):

        -  Participant will have a physical exam.

        -  Photographs will be taken of any lesions on participant's chest.

      On Day 1 of Cycle 9 and then every 4 cycles after that (Cycles 13, 17, 21, and so on):

        -  Blood (about 2 tablespoons) will be drawn for routine tests and tumor marker testing.

        -  Participant will have a CT or PET/CT scan to check the status of the disease.
           Participant may have a bone scan, if PET/CT is not available.

      Length of Treatment:

      Participant may continue taking the study drug for as long as the doctor thinks it is in
      their best interest. Participant will no longer be able to take the study drug if the
      disease gets worse, if intolerable side effects occur, or if they are unable to follow study
      directions.

      Patient's participation on the study will be over after the follow-up visits.

      End-of-Treatment Visit:

      After participant's last dose of study drug but before the start of any new treatments,
      blood (about 2 tablespoons) will be drawn to check their immune system, if possible.

      Follow-Up Visits:

      About 30 days after the end-of-treatment visit and then every 3 months after that for up to
      1 year, participant will have a follow-up visit or phone call to learn how they are doing.
      After 30 days, instead of having a clinic visit, the study staff will review participant's
      medical records. If participant is called, it should take about 2 minutes.

      This is an investigational study. Talimogene laherparepvec (T-VEC) is FDA approved and
      commercially available for the treatment of melanoma. It is considered investigational to
      use T-VEC to treat breast cancer. The study doctor can explain how the study drug is
      designed to work.

      Up to 35 participants will be enrolled in this study. All will take part at MD Anderson.
    

Trial Arms

NameTypeDescriptionInterventions
Talimogene Laherparepvec (T-VEC)ExperimentalTalimogene laherparepvec given via intra-tumoral injection at visible locally recurrent breast cancer site and skin metastases at an initial dose of 10^6 PFU/mL . Second talimogene laherparepvec dose administered 10^8 PFU/mL on Day 22, and talimogene laherparepvec administered every 2 weeks after the second course with same dose with the maximum dose of 4.0 mL for each course.
  • Talimogene Laherparepvec (T-VEC)

Eligibility Criteria

        Inclusion Criteria:

          1. Histological confirmation of breast carcinoma.

          2. Histological confirmation of recurrence of chest wall with or without distant
             metastasis disease.

          3. Patients may have any molecular status (ER, PR and HER2) and must have failed at
             least 1 systemic regimen after their diagnosis of locoregional disease

          4. Previous adjuvant endocrine therapy for initial breast cancer was allowed but had to
             be discontinued at least 1 week before receiving the study drug.

          5. Previous chemotherapy for local recurrence is allowed but must have been discontinued
             at least 4 weeks before receiving the study drug and the patient must have recovered
             from acute adverse effects.

          6. Previous radiation therapy was allowed but must have been discontinued at least 2
             months before study drug is administered, and the patient must have recovered from
             acute toxic effects.

          7. Age >=18 years old

          8. Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1

          9. Adequate hematologic function: 1).Absolute neutrophil count (ANC) >= 1.5x109/L;
             2).Platelet count >= 100x109/L; 3).Hemoglobin >=10.0 g/L. 4).International
             normalization ratio (INR) or prothrombin time (PT) 1.5 x ULN, unless the subject is
             receiving anticoagulant therapy, in which case PT and partial thromboplastin time
             (PTT)/ activated PTT (aPTT) must be within therapeutic range of intended use of
             anticoagulants

         10. Adequate renal function: Calculated creatinine clearance > 30 ml/min

         11. Adequate Hepatic function: a).Aspartate aminotransferase (AST) <= 2.5 x ULN;
             b).Alanine aminotransferase (ALT) <= 2.5 x ULN; c).Total bilirubin <= 1.5 x ULN.

         12. Subjects must be candidate for intralesional injection into cutaneous, subcutaneous
             or nodal tumors with or without image ultrasound guidance defined as one or more of
             the following At least 1 injectable lesion >= 5 mm in longest diameter, multiple
             injectable lesions that in aggregate have a longest diameter of >=5 mm.

         13. Female patients of childbearing potential must have negative urine or serum pregnancy
             test no more than 3 days prior to starting study treatment.

         14. Patients must be able and willing to give written informed consent.

        Exclusion Criteria:

          1. Patients who have operable disease with curable intent, and/or are candidates for
             radiation therapy for local control.

          2. Patients receiving concurrent anti-cancer therapy (chemotherapy, immunotherapy,
             radiation therapy, hormonal therapy, and biological therapy) while taking study
             medication, or have previously received .talimogene laherparepvec or any other
             oncolytic virus.

          3. Patients with metastatic sites that requires chemotherapy and/or non-hormonal
             targeted therapy.

          4. Known active central nervous metastases. Subjects with previously treated brain
             metastases may participate provided they are stable (without evidence of progression
             by imaging for at least four weeks prior to the first dose of trial treatment and any
             neurologic symptoms have returned to baseline), have no evidence of new or enlarging
             brain metastases, and are not using steroids >10 mg/day pf prednisone or equivalent

          5. More than three lesions per organ for visceral metastases except for lung or lymph
             node sites.

          6. History or evidence of symptomatic autoimmune disease (eg, pneumonitis,
             glomerulonephritis, vasculitis, or other), or history of active autoimmune disease
             that has required systemic treatment (ie, use of corticosteroids, immunosuppressive
             drugs or biological agents used for treatment of autoimmune diseases) in past 2
             months prior to enrollment. Replacement therapy (eg, thyroxine for hypothyroidism,
             insulin for diabetes or physiologic corticosteroid replacement therapy for adrenal or
             pituitary insufficiency) is not considered a form of systemic treatment for
             autoimmune disease.

          7. Patients with concurrent disease or condition that would make them inappropriate for
             study participation, or any serious medical disorder that would interfere with
             patients' safety

          8. History of a second cancer, except treated basal cell or squamous cell skin cancer,
             in situ cervical cancer or other cancers for which patients are disease free for at
             least 3 years.

          9. Patients with initial diagnoses of stage IV disease.

         10. Patients with active infection and requiring IV or oral antibiotics

         11. Evidence of immune suppression due to: a) Known human immunodeficiency virus (HIV)
             infection or AIDS; b) Known leukemia or lymphoma; c) Those who require high dose
             steroids or other immunosuppressive agents; d) Known hepatitis B or C infection; e)
             Congenital or acquired cellular and/or humoral immune deficiency; f) other signs or
             symptoms of immune system suppression

         12. Active herpetic skin lesions or prior complication of HSV-1 infections (e.g. herpetic
             encephalitis or keratitis).

         13. Currently pregnant or breast-feeding, or planning to become pregnant during study
             treatment and through 3 months after the last dose of study treatment.

         14. Female subject of childbearing potential who is unwilling to use acceptable method(s)
             of effective contraception during study treatment and through 3 months after the last
             dose of talimogene laherparepvec. (Women of not childbearing potential:
             post-menopausal [age > 55 years with cessation of menses > 12 months or < 55 years
             but not spontaneous menses for at least 2 years or < 55 years and spontaneous menses
             within the past 1 year, but currently amenorrheic (eg, spontaneous or secondary to
             hysterectomy), and with postmenopausal gonadotropin levels (luteinizing hormone and
             follicle-stimulating hormone levels > 40 IU/L) or postmenopausal estradiol levels (<
             5 ng/dL) or according to the definition of "postmenopausal range" for the laboratory
             involved] or who have had a hysterectomy, bilateral salpingectomy, or bilateral
             oophorectomy).

         15. Sexually active subjects and their partners unwilling to use male or female latex
             condom to avoid potential viral transmission during sexual contact while on treatment
             and within 30 days after treatment with talimogene laherparepvec.

         16. Currently enrolled in another clinical trial (exclude non-cancer treatment trail) or
             received an investigational agent within 4 weeks of study initiation

         17. Requires intermittent or chronic treatment with antiherpetic drugs, except for
             topical agents

         18. Patients who is known sensitive to any of the products or components to be
             administered during treatment with talimogene laherparepvec.

         19. Chronic oral or systemic steroid medication use at a dose of >10 mg/d of prednisone
             or equivalent [steroids with low systemic absorption (e.g. triamcinolone
             hexacetonide) injected into joint space are allowed]
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Disease Control Rate
Time Frame:Disease assessments performed up to cycle 10 (approximately 6 months)
Safety Issue:
Description:Disease control rate defined as the percentage of complete response (CR), partial response (PR) or stable disease in overall patients. Response evaluated using RECIST ver.1.1. Disease assessment will be performed at the end of cycle 4, cycle 8 and cycle 10.

Secondary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame:From beginning of treatment to disease progression or death, up to 1 year
Safety Issue:
Description:Definition of PFS is time from treatment initiation until disease progression or death, with progression confirmed after the end of cycle 10.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Trial Keywords

  • Breast Cancer
  • Inflammatory breast cancer
  • IBC
  • Non-inflammatory breast cancer
  • Inoperable local recurrence
  • Talimogene laherparepvec
  • T-VEC
  • OncoVEX GM-CSF

Last Updated

August 1, 2016