Clinical Trials /

Talimogene Laherparepvec With Paclitaxel or Endocrine Therapy in Treating Participants With Metastatic, Unresectable, or Recurrent HER2- Negative Breast Cancer

NCT03554044

Description:

This phase Ib trials studies the side effects and how well talimogene laherparepvec works when given together with paclitaxel or endocrine therapy in treating participants with breast cancer that does not express the human epidermal growth factor receptor 2 (HER2) protein and has spread to other places in the body, cannot be removed by surgery, or has come back after. Biological therapies, such as talimogene laherparepvec, use substances made from living organisms that may attack specific tumor cells and stop them from growing or kill them. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Estrogen can cause the growth of breast cancer cells. Drugs used as endocrine therapy, such as letrozole, anastrozole, exemestane, tamoxifen or fulvestrant, may lessen the amount of estrogen made by the body or may may stop the growth of tumor cells by blocking estrogen from connecting to the cancer cells. Giving talimogene laherparepvec with paclitaxel or endocrine therapy may work better in treating participants with HER2-negative breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Talimogene Laherparepvec With Paclitaxel or Endocrine Therapy in Treating Participants With Metastatic, Unresectable, or Recurrent HER2- Negative Breast Cancer
  • Official Title: A Phase 1b Study of Talimogene Laherparepvec (T-VEC) in Combination With Paclitaxel or Endocrine Therapy in Patients With Metastatic, Unresectable, or Locoregionally Recurrent HER2-Negative Breast Cancer With Evidence of Injectable Disease in the Locoregional Area

Clinical Trial IDs

  • ORG STUDY ID: 17753
  • SECONDARY ID: NCI-2018-00652
  • SECONDARY ID: 17-21623
  • NCT ID: NCT03554044

Conditions

  • Anatomic Stage III Breast Cancer AJCC v8
  • Anatomic Stage IIIA Breast Cancer AJCC v8
  • Anatomic Stage IIIB Breast Cancer AJCC v8
  • Anatomic Stage IIIC Breast Cancer AJCC v8
  • Anatomic Stage IV Breast Cancer AJCC v8
  • Estrogen Receptor Positive
  • HER2/Neu Negative
  • Invasive Breast Carcinoma
  • Prognostic Stage III Breast Cancer AJCC v8
  • Prognostic Stage IIIA Breast Cancer AJCC v8
  • Prognostic Stage IIIB Breast Cancer AJCC v8
  • Prognostic Stage IIIC Breast Cancer AJCC v8
  • Prognostic Stage IV Breast Cancer AJCC v8
  • Recurrent Breast Carcinoma

Interventions

DrugSynonymsArms
AnastrozoleArimidex, ICI-D1033, ZD-1033Cohort II (talimogene laherparepvec, endocrine therapy)
ExemestaneAromasin, FCE-24304Cohort II (talimogene laherparepvec, endocrine therapy)
FulvestrantFaslodex, ICI 182,780, ZD9238Cohort II (talimogene laherparepvec, endocrine therapy)
LetrozoleCGS 20267, FemaraCohort II (talimogene laherparepvec, endocrine therapy)
PaclitaxelAnzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol KonzentratCohort I (talimogene laherparepvec, paclitaxel)
Talimogene LaherparepvecICP34.5-, ICP47-deleted Herpes Simplex Virus 1 (HSV-1) Incorporating the Human GM-CSF Gene, Imlygic, JS1 34.5-hGMCSF 47- pA-, T-VECCohort I (talimogene laherparepvec, paclitaxel)
TamoxifenCohort II (talimogene laherparepvec, endocrine therapy)

Purpose

This phase Ib trials studies the side effects and how well talimogene laherparepvec works when given together with paclitaxel or endocrine therapy in treating participants with breast cancer that does not express the human epidermal growth factor receptor 2 (HER2) protein and has spread to other places in the body, cannot be removed by surgery, or has come back after. Biological therapies, such as talimogene laherparepvec, use substances made from living organisms that may attack specific tumor cells and stop them from growing or kill them. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Estrogen can cause the growth of breast cancer cells. Drugs used as endocrine therapy, such as letrozole, anastrozole, exemestane, tamoxifen or fulvestrant, may lessen the amount of estrogen made by the body or may may stop the growth of tumor cells by blocking estrogen from connecting to the cancer cells. Giving talimogene laherparepvec with paclitaxel or endocrine therapy may work better in treating participants with HER2-negative breast cancer.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To evaluate the safety and tolerability of intra-lesional talimogene laherparepvec
      administration in combination with paclitaxel or endocrine therapy in patients with
      metastatic, unresectable, or locoregionally recurrent HER2-negative breast cancer with
      injectable sites of disease.

      SECONDARY OBJECTIVES:

      I. To evaluate the efficacy of talimogene laherparepvec in combination with paclitaxel in the
      study population using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.

      II. To evaluate the efficacy of talimogene laherparepvec in combination with endocrine
      therapy in the study population using RECIST 1.1 criteria.

      OUTLINE: Participants are assigned to 1 of 2 cohorts.

      COHORT I (PACLITAXEL): Participants receive talimogene laherparepvec intra-tumorally (IT)
      every 2 weeks for the first 12 weeks and then every 3 weeks thereafter. Participants also
      receive paclitaxel intravenously (IV) over 60 minutes on days 1, 8, 15, and 22. Courses
      repeat every 28 days in the absence of disease progression or unacceptable toxicity.

      COHORT II (ENDOCRINE THERAPY): Participants receive talimogene laherparepvec IT every 2 weeks
      for the first 12 weeks and then every 3 weeks thereafter. Participants also receive letrozole
      orally (PO), anastrazole PO, exemestane PO, tamoxifen PO on days 1-28 or fulvestrant
      intramuscularly (IM) every 2 weeks for 3 doses then every 4 weeks for the subsequent courses.
      Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, participants are followed up for 30 days.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort I (talimogene laherparepvec, paclitaxel)ExperimentalParticipants receive talimogene laherparepvec IT every 2 weeks for the first 12 weeks and then every 3 weeks thereafter. Participants also receive paclitaxel IV over 60 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Paclitaxel
Cohort II (talimogene laherparepvec, endocrine therapy)ExperimentalParticipants receive talimogene laherparepvec IT every 2 weeks for the first 12 weeks and then every 3 weeks thereafter. Participants also receive letrozole PO, anastrazole PO, exemestane PO, tamoxifen PO on days 1-28 or fulvestrant IM every 2 weeks for 3 doses then every 4 weeks for the subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Anastrozole
  • Exemestane
  • Fulvestrant
  • Letrozole
  • Tamoxifen

Eligibility Criteria

        Inclusion Criteria:

          -  Metastatic or locoregionally recurrent HER2-negative breast cancer; resectable disease
             allowed

          -  Ability to understand and voluntarily sign informed consent prior to undergoing any
             study-related assessments or procedures, as well as adhere to the study visit schedule
             and other protocol requirements

          -  Histologic or cytologic confirmation of invasive breast cancer that is HER2-negative
             by standard clinical criteria

          -  Patients who will participate in the endocrine therapy cohort must have invasive
             breast cancer that is estrogen receptor (ER)+ (>= 1% ER staining by
             immunohistochemistry [IHC])

          -  At least one accessible and injectable lesion in the locoregional area (ie. breast,
             chest wall, skin nodule or mass, axillary or supraclavicular lymph node) of at least 1
             centimeter (cm); (ultrasound imaging may be used as clinically indicated)

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

          -  Concomitant use of bisphosphonates, receptor activator of nuclear factor kappa-B
             ligand (RANKL) antibody, and ovarian suppression is allowed

          -  Absolute neutrophil count (ANC) ≥ 1.5x10^9/L for paclitaxel cohort, and ≥ 1.0x10^9/L
             for endocrine therapy cohort

          -  Hemoglobin (Hgb) ≥ 9 g/dL

          -  Platelets (plt) ≥ 100 x 10^9/L for paclitaxel cohort, and ≥ 75, 000 for endocrine
             therapy cohort

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper
             limit normal (ULN)

          -  Serum total bilirubin ≤ 1.5 x ULN

          -  Serum creatinine ≤ 1.5 x ULN, or 24-hour (hr) clearance ? 60 ml/min

          -  International normalization ratio (INR) or prothrombin time (PT) ≥ 1.5 x

          -  Females of child-bearing potential (FCBP) should have a negative urine or serum
             pregnancy test within 72 hours prior to enrollment; if urine test is positive or
             cannot be confirmed as negative, a serum pregnancy test will be required; FCBP must
             also be willing to adhere to acceptable forms of birth control (a physician-approved
             contraceptive method: tubal ligation; intra-uterine device; barrier contraceptive with
             spermicide; or vasectomized partner) during the study treatment and through 3 months
             after the last dose of talimogene laherparepvec; FCBP are defined as sexually mature
             women who:

               -  Have not undergone a hysterectomy (the surgical removal of the uterus) or
                  bilateral oophorectomy (the surgical removal of both ovaries) or,

               -  Have not been naturally postmenopausal for at least 12 consecutive months (i.e.
                  has had menses at any time during the preceding 12 consecutive months)

               -  Must be willing to practice abstinence or use effective contraception for a
                  minimum of 3 months following completion of study treatment (in addition to
                  during study therapy)

        Exclusion Criteria:

          -  Any significant medical condition, laboratory abnormalities, which places the subject
             at unacceptable risk if he/she were to participate in the study

          -  Any condition that confounds the ability to interpret data from the study

          -  Patients must have recovered from side effects resulting from prior cancer-directed
             therapy to a level of grade 1 or less (unless deemed not clinically significant by
             study investigator)

          -  Symptomatic central nervous system metastases; subjects with brain metastases that
             have been previously treated and are stable for 4 weeks off steroids are allowed;
             patients must be stable off steroids for brain metastases for at least 7 days;
             subjects with asymptomatic clinically insignificant brain metastases not requiring
             treatment are allowed; the exception does not include carcinomatous meningitis which
             is excluded regardless of clinical stability

          -  Patients with leptomeningeal disease

          -  History of symptomatic autoimmune disease or active autoimmune disease that has
             required systemic treatment in the 2 weeks prior to enrollment; replacement therapy
             (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for
             adrenal or pituitary insufficiency, etc.) is not considered a form of systemic
             treatment

          -  Evidence of immune suppression due to: a) known human immunodeficiency virus (HIV)
             infection or acquired immunodeficiency syndrome (AIDS); b) known leukemia or lymphoma;
             c) those who require high dose steroids (> 10 mg/day of prednisone or equivalent
             within 7 days prior to enrollment) or other immunosuppressive therapies (> 2 weeks);
             d) active hepatitis B or C; e) congenital or acquired cellular and/or humoral immune
             deficiency; f) other signs or symptoms of immune system suppression or concurrent
             opportunistic infection

          -  Paclitaxel arm: grade 2 or higher neuropathy

          -  Known history of: cardiac disease, heart failure or decreased left ventricular
             ejection fraction, significant clinical arrhythmias

          -  Patients must not have received an investigational agent within 4 weeks or ? 5 half
             lives, whichever is shorter, prior to starting study treatment

          -  Last dose of chemotherapy must be at least 3 weeks before first dose of study
             treatment; there is no required washout for endocrine therapy

          -  Major surgery or radiation ≤ 2 weeks prior to starting study treatment or who have not
             recovered from side effects of surgery or radiation

          -  Active herpetic skin lesions or prior complications of HSV-1 infection (e.g. herpetic
             encephalitis or keratitis)

          -  Lesions with underlying infection or clinically meaningful bleeding

          -  Requires intermittent or chronic systemic (intravenous or oral) treatment with an
             antiherpetic drug (e.g. acyclovir), other than intermittent topical use; patients
             requiring anti-herpetic prophylaxis during chemotherapy are excluded

          -  Previous treatment with talimogene laherparepvec or any other oncolytic virus

          -  Prior therapy with tumor vaccine

          -  Received live vaccine within 28 days prior to enrollment

          -  Known allergic reaction to talimogene laherparepvec, paclitaxel, aromatase inhibitors,
             tamoxifen, fulvestrant, or any of their components; an exception is made if the
             patient will not be receiving the offending agent/component (i.e. a patient who is
             allergic to paclitaxel but will be receiving endocrine therapy is eligible)

          -  Patients on therapeutic anticoagulation

          -  Women who are pregnant or breast-feeding

          -  FCBP who are unwilling to use acceptable method(s) of effective contraception during
             study treatment and through 3 months after the last dose of talimogene laherparepvec

          -  Sexually active subjects and their partners unwilling to use a 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

          -  Subjects who are unwilling to minimize exposure with his/her blood or other body
             fluids to individuals who are at higher risks for HSV 1 induced complications
             (immunosuppressed individuals, HIV positive individuals, pregnant women, or children
             under the age of 1 year) during talimogene laherparepvec treatment and through 30 days
             after the last dose of talimogene laherparepvec
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Distribution for the maximum observed grade for each adverse event of talimogene laherparepvec in both arms
Time Frame:Up to 2.5 years
Safety Issue:
Description:The highest grade of all clinically significant AEs possibly related to treatment for each patient will be reported. Treatment-related toxicities will be assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03, for all patients who receive at least one dose of study treatment.

Secondary Outcome Measures

Measure:Overall response rate
Time Frame:From the start of the treatment until disease progression/recurrence (Up to 2.5 years)
Safety Issue:
Description:
Measure:Response duration
Time Frame:From initial response assessed up to 2.5 years
Safety Issue:
Description:Defined as the time from initial response to the first documented tumor progression. ORR, response duration will be

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of California, San Francisco

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