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

NCT03597009 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: LCCC 1626
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Malignant Pleural Effusion; Stage IV Metastatic Cancer; Lung Cancer

Keywords

talimogene laherparepvec; Nivolumab; PleurX

Outcome Measures

Primary Outcomes (2)

• Phase I Number of Participants With Treatment-related Adverse Events

  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.

  from day 1 of treatment to 30 days after the last dose of study medication (approximately 11 weeks)

• Phase II Resolution of MPE

  The rate of resolution of malignant pleural effusion following IV nivolumab combined with intrapleural injection of talimogene laherparepvec

  13 weeks

Secondary Outcomes (5)

• Median Progression Free Survival

  up to 2 years

• Overall Survival

  up to 2 years

• Response Rate

  up to 2 years

• Phase II Number of Participants With Treatment-related Adverse Events

  13 weeks

• Average Dyspnea Score

  13 weeks

Study Arms (1)

Open-label, single-arm Phase I

EXPERIMENTAL

Talimogene laherparepvec (TVEC) administered into the intrapleural space of subjects with malignant pleural effusion (MPE) via a pleurX catheter with or without nivolumab

Drug: Talimogene laherparepvec (TVEC); Drug: Nivolumab

Interventions

Talimogene laherparepvec (TVEC) DRUG

Talimogene laherparepvec (TVEC) (4ml of 108 pfu/ml) for up to 9 cycles, with or without nivolumab

Also known as: Imlygic, OncoVex

Open-label, single-arm Phase I

Nivolumab DRUG

Nivolumab (240 mg IV) will be co-administered with talimogene laherparepvec (TVEC) (4ml of 108 pfu/ml) for up to 9 cycles in the Dose Level 2 cohort

Also known as: Opdivo

Open-label, single-arm Phase I

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be ≥ 18 years of age on day of signing informed consent.
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
• Histologically or cytologically confirmed stage IV metastatic cancer.
• 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
• 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.
• 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.
• 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.

You may not qualify if:

• 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.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1
• 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).
• 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).
• 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.
• Major surgery within 28 days prior to day 1 of study treatment from which the patient has not completely recovered.
• 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.
• 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.
• Has a history of non-infectious pneumonitis that required steroids; currently active non-infectious pneumonitis; or evidence of interstitial lung disease.
• Has an active infection requiring systemic therapy or history of uncontrolled infection.
• 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.
• Has inadequate home environment or social support to safely complete the trial procedures
• Is pregnant or breastfeeding
• Known human immunodeficiency virus (HIV), hepatitis C virus (HCV) or evidence of active hepatitis B virus (HBV).
• Has a multi-loculated pleural effusion that would not lead to relief of dyspnea from drainage of a single loculation.

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• C. R. Bard: collaborator
• Amgen: collaborator

Study Sites (1)

Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Related Links

• University of North Carolina (UNC) Lineberger Comprehensive Cancer Center Clinical Trials

MeSH Terms

Conditions

Pleural Effusion, Malignant; Neoplasm Metastasis; Lung Neoplasms

Interventions

talimogene laherparepvec; Nivolumab

Condition Hierarchy (Ancestors)

Pleural Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Pleural Effusion; Pleural Diseases; Respiratory Tract Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lung Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Study terminated early due to slow accrual and withdrawal of funding so only one participant was enrolled.

Results Point of Contact

• Title: Robin Johnson
• Organization: University of North Carolina Lineberger Comprehensive Cancer Center

robin_v_johnson@med.unc.edu

919-966-1125

Study Officials

• Jared Weiss, MD

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: We will conduct a Phase Ib/II trial that includes a safety run-in period using 3 +3 dose escalation rules to evaluate the feasibility of administering talimogene laherparepvec into the intrapleural space of subjects with malignant pleural effusion (MPE) via a pleurX catheter.

Study Record Dates

• First Submitted: June 1, 2018
• First Posted: July 24, 2018
• Study Start: March 6, 2019
• Primary Completion: February 7, 2020
• Study Completion: February 12, 2020
• Last Updated: April 20, 2021
• Results First Posted: April 20, 2021

Record last verified: 2021-03

Locations

US (1)