Malignant Pleural EffusionPhase 1/2NCT03597009
A Study of Nivolumab and Intrapleural Talimogene Laherparepvec for Malignant Pleural Effusion
A Phase 1/2 study testing Talimogene laherparepvec (TVEC) and Nivolumab in people with Malignant Pleural Effusion and Stage IV Metastatic Cancer, run by UNC Lineberger Comprehensive Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Malignant Pleural Effusion, Stage IV Metastatic Cancer, Lung Cancer
- What is being tested?
- Talimogene laherparepvec (TVEC) and Nivolumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Mar 2019to 12 Feb 2020
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must meet the following inclusion criteria to participate in this study:
- 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
- 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.
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- 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.
Who cannot join
- Patients meeting any of the following exclusion criteria will not be able to participate in this study:
- 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.
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- 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.
- Current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, or stable chronic liver disease per investigator assessment).
- 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.
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
About this study
Official title: A Phase Ib/II Study of IV Nivolumab and Intrapleural Talimogene Laherparepvec for Patients With Malignant Pleural Effusion
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.
Read the 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.
- Being tested
- Talimogene laherparepvec (TVEC), Nivolumab
- Keywords
- talimogene laherparepvec, Nivolumab, PleurX
- Medical subject headings
- Pleural Effusion, Malignant, Neoplasm Metastasis, Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Talimogene laherparepvec (TVEC)Drug
Also called Imlygic, OncoVex
Talimogene laherparepvec (TVEC) (4ml of 108 pfu/ml) for up to 9 cycles, with or without nivolumab
NivolumabDrug
Also called Opdivo
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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Talimogene laherparepvec (TVEC); Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 13 weeks
Secondary outcomes (5)
Median Progression Free Survival
Progression free survival from day 1 of treatment until death or progression. Per immune-related Response Evaluation Criteria in Solid Tumours (irRECIST), immune-related Progressive Disease (irPD)is defined as at least 20% and minimum 5 mm absolute increase in total measured tumor burden compared to nadir, or irPD for non-target or new un-measurable lesions.
Measured: up to 2 years
Overall Survival
Overall survival from day 1 of treatment until death
Measured: up to 2 years
Response Rate
Response rate after treatment per Immune-Related Response Evaluation Criteria In Solid Tumors (irRECIST) defined as the proportion of patients with reduction in tumor (immune-related Complete Response (irCR) or immune-related Partial Response (irPR)). irCR is a complete disappearance of all lesions (whether measurable or not) and no new lesions. Lymph nodes must decrease to <10mm in short axis. irPR is a decrease in tumor burden ≥ 30%, in total measured tumor burden relative to baseline, non-target lesions are not in complete response (disappearance of all lesions) and not unequivocal progression or new non-measurable lesions.
Measured: up to 2 years
Phase II 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.
Measured: 13 weeks
Average Dyspnea Score
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.
Measured: 13 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2018
- Study start6 Mar 2019
- Primary completion7 Feb 2020
- Study completion12 Feb 2020
Why it stopped: due to slow accrual and withdrawal of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Malignant Pleural EffusionStudies of the same condition, open and under way.
- More trials run by UNC Lineberger Comprehensive Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- UNC Lineberger Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- C. R. Bard, Amgen
- Responsible party
- Sponsor
- Investigators
- Jared Weiss, MD, Principal investigator, UNC Lineberger Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03597009
- Sponsor's protocol ID
- LCCC 1626
- Status last verified
- Mar 2021
- First submitted
- 1 Jun 2018
- Last updated
- 20 Apr 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib/II Study of IV Nivolumab and Intrapleural Talimogene Laherparepvec for Patients With Malignant Pleural Effusion
- ClinicalTrials.gov ID
- NCT03597009
- Acronym / sponsor ID
- LCCC 1626
- Keywords
- talimogene laherparepvec, Nivolumab, PleurX
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: due to slow accrual and withdrawal of funding
- Enrolment
- 1 participants (actual)
- Lead sponsor
- UNC Lineberger Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- C. R. Bard, Amgen
- Study start
- 6 Mar 2019 (actual)
- Primary completion
- 7 Feb 2020 (actual)
- Study completion
- 12 Feb 2020 (actual)
- First posted
- 24 Jul 2018 (actual)
- Results
- Posted 20 Apr 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Open-label, single-arm Phase I | Experimental | Drug: Talimogene laherparepvec (TVEC), Drug: NivolumabTalimogene laherparepvec (TVEC) administered into the intrapleural space of subjects with malignant pleural effusion (MPE) via a pleurX catheter with or without nivolumab |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
- 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.
Key exclusion criteria (19 listed)
- Patients meeting any of the following exclusion criteria will not be able to participate in this study:
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Talimogene laherparepvec (TVEC)Also: Imlygic, OncoVexTalimogene laherparepvec (TVEC) (4ml of 108 pfu/ml) for up to 9 cycles, with or without nivolumab | Drug | Open-label, single-arm Phase I |
| NivolumabAlso: OpdivoNivolumab (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 | Drug | Open-label, single-arm Phase I |
Primary outcome
Phase I Number of Participants With Treatment-related Adverse Events
Time frame: from day 1 of treatment to 30 days after the last dose of study medication (approximately 11 weeks)
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.
Phase II Resolution of MPE
Time frame: 13 weeks
The rate of resolution of malignant pleural effusion following IV nivolumab combined with intrapleural injection of talimogene laherparepvec
5 secondary outcomes
Median Progression Free Survival
Time frame: up to 2 years
Overall Survival
Time frame: up to 2 years
Response Rate
Time frame: up to 2 years
Phase II Number of Participants With Treatment-related Adverse Events
Time frame: 13 weeks
Average Dyspnea Score
Time frame: 13 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- University of North Carolina (UNC) Lineberger Comprehensive Cancer Center Clinical TrialsLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jared Weiss, MD principal investigator
UNC Lineberger Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Talimogene laherparepvec (TVEC) and Nivolumab in people with Malignant Pleural Effusion and Stage IV Metastatic Cancer, run by UNC Lineberger Comprehensive Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 20 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase I Number of Participants With Treatment-related Adverse Events (time frame: from day 1 of treatment to 30 days after the last dose of study medication (approximately 11 weeks)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Apr 2021; AzTrials last refreshed its copy on 8 Nov 2026.