Clinical Trials /

Talimogene Laherparepvec and Panitumumab for the Treatment of Locally Advanced or Metastatic Squamous Cell Carcinoma of the Skin

NCT04163952

Description:

This phase I trial studies the side effects and how well talimogene laherparepvec and panitumumab work in treating patients with squamous cell carcinoma of the skin that has spread to nearby tissues or lymph nodes (locally advanced) or other places in the body (metastatic). Talimogene laherparepvec is a type of vaccine made from a gene-modified virus that may help the body build an effective immune response to kill tumor cells. Immunotherapy with monoclonal antibodies, such as panitumumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving talimogene laherparepvec and panitumumab may work better in treating patients with squamous cell carcinoma of the skin compared to panitumumab alone.

Related Conditions:
  • Skin Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Talimogene Laherparepvec and Panitumumab for the Treatment of Locally Advanced or Metastatic Squamous Cell Carcinoma of the Skin
  • Official Title: A Phase 1 Study of Talimogene Laherparepvec and Panitumumab in Patients With Locally Advanced Squamous Cell Carcinoma of the Skin (SCCS)

Clinical Trial IDs

  • ORG STUDY ID: 091804
  • SECONDARY ID: NCI-2019-06083
  • SECONDARY ID: Pro2018002628
  • SECONDARY ID: 091804
  • SECONDARY ID: P30CA072720
  • NCT ID: NCT04163952

Conditions

  • Locally Advanced Skin Squamous Cell Carcinoma
  • Metastatic Skin Squamous Cell Carcinoma
  • Recurrent Skin Squamous Cell Carcinoma

Interventions

DrugSynonymsArms
PanitumumabABX-EGF, ABX-EGF Monoclonal Antibody, ABX-EGF, Clone E7.6.3, MoAb ABX-EGF, Monoclonal Antibody ABX-EGF, VectibixTreatment (talimogene laherparepvec, panitumumab)
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-VECTreatment (talimogene laherparepvec, panitumumab)

Purpose

This phase I trial studies the side effects and how well talimogene laherparepvec and panitumumab work in treating patients with squamous cell carcinoma of the skin that has spread to nearby tissues or lymph nodes (locally advanced) or other places in the body (metastatic). Talimogene laherparepvec is a type of vaccine made from a gene-modified virus that may help the body build an effective immune response to kill tumor cells. Immunotherapy with monoclonal antibodies, such as panitumumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving talimogene laherparepvec and panitumumab may work better in treating patients with squamous cell carcinoma of the skin compared to panitumumab alone.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the safety of the combined treatment of talimogene laherparepvec and
      panitumumab.

      II. To determine the preliminary efficacy of the combined treatment of talimogene
      laherparepvec and panitumumab, in comparison to single-agent panitumumab by historical
      control.

      SECONDARY OBJECTIVES:

      I. To assess the clinical efficacy of panitumumab in combination with intratumoral talimogene
      laherparepvec in terms of immune-related progression-free survival (irPFS) at 12 months,
      progression-free survival (PFS) hazard ratio, overall response rate (ORR), 1-year survival,
      overall survival (OS) and time to resectability.

      II. To measure the pathologic complete response rate to panitumumab combined with talimogene
      laherparepvec.

      III. Assess the response of injected and non-injected tumor deposits after panitumumab and
      talimogene laherparepvec.

      IV. Assess the time to initial response. V. Assess the durable response rate.

      VI. To analyze the following molecular correlates with response to therapy to confirm
      mechanism of action, and identify potential future targeted strategies and biomarkers of
      response:

      VIa. Mutation load in tumor tissue by next generation sequencing. VIb. Deoxyribonucleic acid
      (DNA) mutation signature in tumor tissue pre- and post-therapy by next generation sequencing.

      VIc. Messenger ribonucleic acid (mRNA) signature in tumor tissue pre-and post-therapy by
      Nanostring technology.

      VId. Immune cell populations and immune profile in pre- and post-therapy tumor tissue and
      peripheral blood by flow cytometry and immunohistochemistry (IHC).

      OUTLINE:

      Patients receive talimogene laherparepvec intratumorally (IM) on day 1. Patients then receive
      talimogene laherparepvec IM and panitumumab intravenously (IV) over 30-90 minutes on day 22.
      Treatment repeats every 2 weeks for up to 3 cycles in the absence of disease progression or
      unacceptable toxicity. Patients may receive up to 3 additional cycles of treatment per
      physician discretion.

      After completion of study treatment, patients are followed up at 30 days and then every 2
      months for 2 years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (talimogene laherparepvec, panitumumab)ExperimentalPatients receive talimogene laherparepvec IM on day 1. Patients then receive talimogene laherparepvec IM and panitumumab IV over 30-90 minutes on day 22. Treatment repeats every 2 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients may receive up to 3 additional cycles of treatment per physician discretion.
  • Panitumumab
  • Talimogene Laherparepvec

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed squamous cell carcinoma of the skin (SCCS) that is a) locally
             advanced or metastatic for which curative surgery or radiation would be difficult or
             impossible, or b) recurrent after initial surgery, chemotherapy, or radiation therapy,
             or c) considered to have aggressive features including the following: tumors 2 cm or
             more, tumors invading deep tissues such as muscle, cartilage or bone; tumors showing
             perineural invasion, and/or tumors metastatic to loco-regional lymph nodes. Patients
             may have had prior surgical interventions or been treated with investigational agents
             with residual or recurrent disease

          -  Tumor suitable for direct or ultrasound-guided injection defined as at least one
             cutaneous, subcutaneous, or nodal lesion, or aggregate of lesions, >= 10 mm in
             diameter

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2

          -  No prior treatment with panitumumab or talimogene laherparepvec for advanced disease

          -  Prior surgery or radiation is allowed if there is documented progression in the
             radiated/resected area or elsewhere by Response Evaluation Criteria in Solid Tumors
             (RECIST) criteria version (v) 1.1

          -  Measurable disease by RECIST criteria v 1.1

          -  Patients with a history of hematologic or solid organ transplant will be considered if
             they do not require high dose steroids or high dose immunosupressants for disease
             control or control of transplant rejection, and have adequate hematologic, renal, and
             hepatic function as specified below. Current medications must be reviewed with
             transplant pharmacy team to exclude potentially serious interactions and case
             discussed with the study principal investigator (PI)

          -  Second primary malignancy only if treatment would interfere with the patient?s
             participation in this trial in the opinion of the treating physician. Clear exceptions
             are 1) patient had a second primary malignancy but has been treated and disease free
             for at least 3 years, 2) in situ carcinoma (e.g., in situ carcinoma of the cervix)
             and, 3) additional skin cancers that have been definitively treated by surgery and/or
             radiation. Patients with chronic lymphocytic leukemia will be allowed if their blood
             counts are within acceptable hematologic parameters and if they are not currently
             requiring cytotoxic or biologic anticancer treatment (supportive treatment such as
             intravenous immunoglobulin [IVIG] is permitted)

          -  Patients with autoimmune disorders will be considered if they do not require high dose
             steroids or other immunosuppressants for disease control. Prednisone in daily doses up
             to 10 mg and inhaled steroids are acceptable

          -  Absolute neutrophil count (ANC) >= 1500/uL

          -  Platelet count >= 100,000/mm^2

          -  Hemoglobin >= 9 g/dL

          -  Total bilirubin < 1.5 x institutional upper limit of normal (ULN); if patient has
             conditions of congenital hyperbilirubinemia, then patient must have isolated
             hyperbilirubinemia (e.g., no other liver function test abnormalities) with maximum
             bilirubin < 2 x institutional ULN

          -  Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 x
             institutional ULN in absence of liver metastases; =< 5 x ULN in presence of liver
             metastases

          -  Alkaline phosphatase < 2.5 x institutional ULN

          -  Creatinine < 1.5 x institutional ULN or calculated creatinine clearance >= 60 mL/min
             as estimated using the Cockcroft-Gault formula

        Exclusion Criteria:

          -  Pregnant women. Women of childbearing age must be willing to undergo a pregnancy test
             prior to therapy and to use adequate contraception (e.g., hormonal or barrier method
             of contraception or abstinence) for the duration of the study and 6 months thereafter.
             Should a woman become pregnant or suspect she is pregnant while participating in this
             study, she should inform her treating physician immediately. Menopausal status will be
             defined as one or more of successful hysterectomy, bilateral tubal ligation or
             bilateral oophorectomy, amenorrhea >= 12 consecutive months without another cause, or
             a documented serum follicle stimulating hormone (FSH) >= 35 mIU/mL

          -  Tumor not suitable for direct or ultrasound-guided injection

          -  Prior treatment with talimogene laherparepvec for advanced disease

          -  Patients with active, uncontrolled infections including active herpetic infections or
             chronic herpetic infections requiring anti-viral therapy (e.g., acyclovir)

          -  Patients without adequate organ function as documented above

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to panitumumab, talimogene laherparepvec or other agents used in the study

          -  History of interstitial pneumonitis, pulmonary fibrosis, or evidence of interstitial
             pneumonitis
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events
Time Frame:Up to 30 days
Safety Issue:
Description:Will be based on National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.

Secondary Outcome Measures

Measure:Best overall response rate (ORR)
Time Frame:Up to 2 years
Safety Issue:
Description:Will be defined as the best response as recorded from the start of study drug until disease progression. ORR is defined as the proportion of patients with a best ORR characterized as either a complete response or partial response relative to the total number of evaluable patients. The response rate of the drug will be assessed according to the decision rule based on Simon?s two-stage design.
Measure:Durable response rate
Time Frame:Up to 2 years
Safety Issue:
Description:Will be defined as the percent of patients with complete response or partial response maintained continuously for a minimum of 6 months. The response rate of the drug will be assessed according to the decision rule based on Simon?s two-stage design.
Measure:Duration of response
Time Frame:Time from initial response until document progression, assessed up to 2 years
Safety Issue:
Description:The response rate of the drug will be assessed according to the decision rule based on Simon?s two-stage design.
Measure:Progression-free survival (PFS)
Time Frame:From date of enrollment to the date of death or progression, whichever occurred earlier (per RECIST 1.1), assessed up to 2 years
Safety Issue:
Description:The estimate of PFS will be performed by the Kaplan-Meier product limit model. Logrank test and Cox proportional hazards model will be used to explore the associations between PFS and patient characteristics.
Measure:Overall survival (OS)
Time Frame:From date of enrollment to the date of death or date last known alive, assessed up to 2 years
Safety Issue:
Description:The estimate of OS will be performed by the Kaplan-Meier product limit model. Logrank test and Cox proportional hazards model will be used to explore the associations between OS and patient characteristics.
Measure:Mutation load in tumor tissue
Time Frame:Up to 2 years
Safety Issue:
Description:Will be analyzed by next generation sequencing with response to therapy. Molecular correlates will also be obtained and descriptive statistics applied.
Measure:Deoxyribonucleic acid mutation signature in tumor tissue
Time Frame:Up to 2 years
Safety Issue:
Description:Will be analyzed by next generation sequencing with response to therapy. Molecular correlates will also be obtained and descriptive statistics applied.
Measure:Messenger ribonucleic acid signature in tumor tissue
Time Frame:Up to 2 years
Safety Issue:
Description:Will be analyzed by Nanostring technology with response to therapy. Molecular correlates will also be obtained and descriptive statistics applied.
Measure:Immune cell populations in tumor tissue
Time Frame:Up to 2 years
Safety Issue:
Description:Will be analyzed by flow cytometry and immunohistochemistry with response to therapy. Molecular correlates will also be obtained and descriptive statistics applied.
Measure:Immune cell populations peripheral blood
Time Frame:Up to 2 years
Safety Issue:
Description:Will be analyzed by flow cytometry and immunohistochemistry with response to therapy. Molecular correlates will also be obtained and descriptive statistics applied.
Measure:Expression of Cytokines in tumor tissue
Time Frame:Up to 2 years
Safety Issue:
Description:Will be analyzed by flow cytometry and immunohistochemistry with response to therapy. Molecular correlates will also be obtained and descriptive statistics applied.
Measure:Expression of Cytokines in peripheral blood
Time Frame:Up to 2 years
Safety Issue:
Description:Will be analyzed by flow cytometry and immunohistochemistry with response to therapy. Molecular correlates will also be obtained and descriptive statistics applied.
Measure:Pathologic complete response rate
Time Frame:Up to 2 years
Safety Issue:
Description:
Measure:Time to resectability
Time Frame:Up to 2 years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Rutgers, The State University of New Jersey

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