Clinical Trials /

A Study of Nivolumab and Intrapleural Talimogene Laherparepvec for Malignant Pleural Effusion

NCT03597009

Description:

This is a Phase Ib/II clinical trial to evaluate the feasibility of administering talimogene laherparepvec into the intrapleural space of subjects with malignant pleural effusion through a pleurX catheter.

Related Conditions:
  • Lung Carcinoma
  • Malignant Pleural Neoplasm
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Nivolumab and Intrapleural Talimogene Laherparepvec for Malignant Pleural Effusion
  • Official Title: A Phase Ib/II Study of IV Nivolumab and Intrapleural Talimogene Laherparepvec for Patients With Malignant Pleural Effusion

Clinical Trial IDs

  • ORG STUDY ID: LCCC 1626
  • NCT ID: NCT03597009

Conditions

  • Malignant Pleural Effusion
  • Stage IV Metastatic Cancer
  • Lung Cancer

Interventions

DrugSynonymsArms
Talimogene laherparepvec (TVEC)Imlygic, OncoVexOpen-label, single-arm Phase I
NivolumabOpdivoOpen-label, single-arm Phase I

Purpose

This is a Phase Ib/II clinical trial to evaluate the feasibility of administering talimogene laherparepvec into the intrapleural space of subjects with malignant pleural effusion through a pleurX catheter.

Detailed Description

      This is a phase 1b/II clinical trial that includes a safety run-in cohort to investigate the
      novel approach of administering intrapleural talimogene laherparepvec via a pleurX catheter
      in patients with known malignant pleural effusion (MPE).

      In Phase Ib of this study, the safety of infusing talimogene laherparepvec directly into the
      pleural cavity of subjects diagnosed with MPE, through pleurX catheter, will be tested.

      In Phase II of this study, after establishing the safety of the above mentioned approach, 24
      subjects will enrolled and treated with intrapleural talimogene laherparepvec and IV
      nivolumab.
    

Trial Arms

NameTypeDescriptionInterventions
Open-label, single-arm Phase IExperimentalTalimogene laherparepvec (TVEC) administered into the intrapleural space of subjects with malignant pleural effusion (MPE) via a pleurX catheter with or without nivolumab
  • Talimogene laherparepvec (TVEC)
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

        Patients must meet the following inclusion criteria to participate in this study:

          1. Be ≥ 18 years of age on day of signing informed consent.

          2. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2

          3. Histologically or cytologically confirmed stage IV metastatic cancer.

          4. Confirmation of malignant pleural effusion via imaging (Computer tomography (CT) scan,
             chest x-ray (CXR), MRI, ultrasound, Positron Emission Tomography (PET)/CT), and
             cytology for which pleurX catheter placement is standard of care

          5. Recovered from all reversible toxicities related to their previous treatment (other
             than alopecia) to ≤grade 1 or baseline; exceptions to this criterion may be allowed
             following review by the principal investigator for toxicities that are not expected to
             be exacerbated by nivolumab or talimogene laherparepvec. Grade 2 peripheral neuropathy
             will not result in exclusion as neither study agent would be expected to exacerbate
             it.

          6. No history of untreated brain metastasis. Treated brain metastases must not be known
             to be progressive, symptomatic, or currently requiring > 10 mg of prednisone or
             prednisone equivalents within two weeks prior to study drug administration.

          7. Females of childbearing potential must have a negative serum pregnancy test within 72
             hours prior to receiving the first dose of study medication. Females of childbearing
             potential must agree to use 2 methods of effective contraception or abstain from
             heterosexual sex throughout the treatment period and for 5 months after the last dose
             of study treatment. Females of childbearing potential are women who have not been
             surgically sterilized (have undergone a hysterectomy, bilateral tubal ligation, or
             bilateral oophorectomy) or have not been free of menses for >1 year.

          8. Male patients with female partners must have had a prior vasectomy or agree to use an
             adequate method of contraception (i.e. double barrier method: condom plus spermicidal
             agent) starting with the first dose of study therapy through 7 months after the last
             dose of study treatment.

        Exclusion Criteria:

        Patients meeting any of the following exclusion criteria will not be able to participate in
        this study:

          1. Receiving any investigational agent, or using an investigational device, currently or
             within 28 days or 5 half-lives of Day 1 of treatment on this study, whichever is
             longer.

          2. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
             within 2 weeks prior to study Day 1

          3. Has had a prior monoclonal antibody within 4 weeks prior to study Day 1, or who has
             not recovered to, ≤ Grade 1 toxicity at baselines from adverse events due to agents
             administered more than 4 weeks earlier. Exceptions to these criteria may be allowed at
             the discretion of the investigator for toxicities that are not expected to be
             exacerbated by nivolumab or talimogene laherparepvec (e.g., alopecia, peripheral
             neuropathy, etc).

          4. Has received prior therapy with an anti-programmed cell death receptor (PD)-1,
             anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated
             antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug
             specifically targeting T-cell co-stimulation or checkpoint pathways).

          5. Any concurrent chemotherapy, intraperitoneal (IP), biologic or hormonal therapy for
             cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions
             (e.g., hormone replacement therapy) is acceptable.

          6. Major surgery within 28 days prior to day 1 of study treatment from which the patient
             has not completely recovered.

          7. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
             other form of immunosuppressive therapy within 7 days prior to the first dose of trial
             treatment.

          8. Has a known secondary malignancy that is progressing or requires active treatment.
             Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the
             skin, or in situ cervical cancer that has undergone potentially curative therapy.

          9. Has a history of non-infectious pneumonitis that required steroids; currently active
             non-infectious pneumonitis; or evidence of interstitial lung disease.

         10. Has an active infection requiring systemic therapy or history of uncontrolled
             infection.

         11. Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the trial, interfere with the subject's
             participation for the full duration of the trial, or is not in the best interest of
             the subject to participate, in the opinion of the treating investigator. This includes
             known psychiatric or substance abuse disorders that would interfere with cooperation
             with the requirements of the trial. This also includes unstable angina, serious
             uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardial infarction ≤ 6
             months prior to study entry.

         12. Has inadequate home environment or social support to safely complete the trial
             procedures

         13. Is pregnant or breastfeeding

         14. Known human immunodeficiency virus (HIV), hepatitis C virus (HCV) or evidence of
             active hepatitis B virus (HBV).

         15. Has a multi-loculated pleural effusion that would not lead to relief of dyspnea from
             drainage of a single loculation.

         16. Current active hepatic or biliary disease (with exception of patients with Gilbert's
             syndrome, asymptomatic gallstones, or stable chronic liver disease per investigator
             assessment).

         17. Active herpetic skin lesions or prior complications of herpetic infection or requires
             intermittent or chronic systemic (intravenous or oral) treatment with an antiherpetic
             drug (e.g., acyclovir), other than intermittent topical use.

         18. Has an active autoimmune disease requiring systemic treatment within the past 3 months
             or a documented history of clinically severe autoimmune disease, or a syndrome that
             requires systemic steroids or immunosuppressive agents; subjects with resolved
             childhood asthma/atopy would be an exception to this rule. Subjects that require
             intermittent use of bronchodilators or local steroid injections would not be excluded
             from the study. Subjects with hypothyroidism stable on hormone replacement or
             Sjorgen's syndrome will not be excluded from the study. 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.
             Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment
             (within the past 2 years) are not excluded.
      
Maximum Eligible Age:99 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase I Number of participants with treatment-related adverse events
Time Frame:7 weeks
Safety Issue:
Description:Number of participants with treatment-related adverse events as assessed by the NCI Common Terminology Criteria for Adverse Events which is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.

Secondary Outcome Measures

Measure:Median Progression free survival
Time Frame:2 years
Safety Issue:
Description:Progression free survival from day 1 of treatment until death or progression
Measure:Overall Survival
Time Frame:2 years
Safety Issue:
Description:Overall survival from day 1 of treatment until death
Measure:Response Rate
Time Frame:2 years
Safety Issue:
Description:Response rate after treatment per Immune-Related Response Evaluation Criteria In Solid Tumors (irRECIST)
Measure:Phase II Number of participants with treatment-related adverse events
Time Frame:13 weeks
Safety Issue:
Description:Number of participants with treatment-related adverse events as assessed by the NCI Common Terminology Criteria for Adverse Events which is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.
Measure:Average Dyspnea Score
Time Frame:13 weeks
Safety Issue:
Description:Results from patient reports of the Modified Borg Scale of Perceived Dyspnea, measuring change in scale over time. The scale evaluates perceived level of shortness of breath ranging from 0 to 10, where 0 indicates the greatest success of the treatment.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:UNC Lineberger Comprehensive Cancer Center

Trial Keywords

  • talimogene laherparepvec
  • Nivolumab
  • PleurX

Last Updated