Non-small Cell Lung Cancer Stage IPhase 1NSCLCNCT03029871
Oncolytic Adenovirus-Mediated Gene Therapy for Lung Cancer
A Phase 1 study testing Ad5-yCD/mutTKSR39rep-ADP Adenovirus in people with Non-small Cell Lung Cancer Stage I, run by Benjamin Movsas, M.D. at 1 site in United States.
Trial summary
The primary objective of this phase 1 trial is to determine the dose-dependent toxicity and maximum tolerated dose (MTD) of oncolytic adenovirus-mediated cytotoxic gene therapy in combination with SBRT in medically inoperable stage I/IIA (T1A - T2B) NSCLC. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer Stage I
- What is being tested?
- Ad5-yCD/mutTKSR39rep-ADP Adenovirus
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Jan 2017to 31 Dec 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Pathologically (histologically or cytologically) proven diagnosis of NSCLC.
- Clinical stage I/IIA (T1a - T2b; AJCC Staging 7th edition) with a tumor size > 1 cm to ≤ 6 cm in diameter (long axis) based on the following minimum diagnostic workup:
- Note: Subjects may have M0 or MX status (e.g., lung nodules that are being observed). Known M1 disease is excluded. Subjects may have only one target lesion for SBRT.
- Evaluation at lung multi-disciplinary tumor board with recommendation for SBRT within 12 weeks of registration.
- Whole body positron emission tomography (PET/CT) scan within 12 weeks of registration using [18F]-FDG with adequate visualization of the primary tumor and draining lymph node basins in the hilar and mediastinal regions.
- Mediastinal lymph node sampling by any technique is allowed but not required. Subjects with > 1.5 cm mediastinal lymph nodes on CT or abnormal PET (including suspicious but non-diagnostic uptake) may still be eligible if directed tissue biopsies of abnormally identified areas are negative for cancer.
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- Zubrod Performance Status 0 - 2 with 4 weeks of registration.
- Age ≥ 18.
- Subjects must have adequate baseline organ function, as assessed by the following laboratory values, within 30 days before initiating the study therapy:
- Adequate renal function with serum creatinine ≤ 1.5 mg/dL or creatinine clearance >50 mL/min/m2.
- Platelet count > 100,000/μL.
- Absolute neutrophil count > 1,000/μL.
- Hemoglobin > 10.0 g/dL.
- Bilirubin > 1.5 mg/dL
- AST/SGOT and ALT/SGPT < 3.0 times upper limit of normal (ULN).
- Negative serum or urine pregnancy test within 72 hours prior to the adenovirus injection for women of childbearing potential.
- Women of childbearing potential and male participants must agree to use a medically effective means of birth control throughout and for 60 days beyond the treatment phase of the study.
- Subjects must possess the ability to give informed consent and express a willingness to meet all of the expected requirements of the protocol for the duration of the study.
Who cannot join
- Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 2 years (e.g., carcinomas in situ of the breast, oral cavity, or cervix are permissible). Subjects with previous lung cancer are permitted if the subject is disease-free for a minimum of 2 years or if this is a solitary recurrence in the lung measuring > 2 cm and ≤ 5 cm after surgery.
- Any known metastatic disease. Subjects may have MX status (e.g., lung nodules that are being observed).
- Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields.
- Prior chemotherapy for the study cancer.
- Plans for the subject to receive other local therapy (including standard fractionated radiotherapy and/or surgery and/or other local ablative therapies) while on this study, except in the case of disease progression.
- Plans for the subject to receive systemic therapy (including standard chemotherapy or biologic targeted agents), while on this study, except in the case of disease progression.
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- Acute infection. Acute infection is defined by any viral, bacterial, or fungal infection that requires specific therapy within 72 hours of initiation of the study therapy.
- Previous history of liver disease including hepatitis.
- Immunosuppressive therapy including systemic corticosteroids. Use of inhaled and topical corticosteroids is permitted.
- Impaired immunity or susceptibility to serious viral infections.
- Allergy to any product used in the protocol.
- Serious medical or psychiatric illness or concomitant medication, which, in the judgment of the principal investigator, might interfere with the subject's ability to respond to or tolerate the treatment or complete the trial.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase 1 Trial of Oncolytic Adenovirus-Mediated Cytotoxic Gene Therapy in Combination With Stereotactic Body Radiation Therapy (SBRT) in Clinical Stage 1/11A (T1A-T2B) Non-Small Cell Lung Cancer
The primary objective of this phase 1 trial is to determine the dose-dependent toxicity and maximum tolerated dose (MTD) of oncolytic adenovirus-mediated cytotoxic gene therapy in combination with SBRT in medically inoperable stage I/IIA (T1A - T2B) NSCLC. To accomplish this objective, 9 subjects will be enrolled in the study. We hypothesize that the combined treatment will demonstrate acceptable toxicity, and that it will be feasible to quantify adenovirus-mediated HSV-1 TK gene expression in the lung by PET. This phase 1 trial will lay the foundation for a follow-up phase 2 trial designed to examine efficacy.
Read the detailed description
Nine subjects (3 cohorts, 3 subjects/cohort) with medically inoperable stage I/IIA (T1a - T2b) NSCLC with tumors measuring > 2 to ≤ 5 cm will receive a single intratumoral injection of the oncolytic Ad5-yCD/mutTKSR39rep-ADP adenovirus at one of three dose levels (1 x 1011 vp, 3 x 1011 vp, 1 x 1012 vp). Depending on the location of the target lesion, the adenovirus will be injected either transbronchially (central tumors) or percutaneously under computed tomography (CT)-guidance (peripheral tumors). Two days later, subjects will be administered (orally) a 10 day course of 5-fluorocytosine (5-FC) and valganciclovir (vGCV) prodrug therapy along with 48 Gy (4 fractions of 12 Gy) of SBRT. Prior to and following the adenovirus injection, subjects will be administered [18F]-FHBG, a HSV-1 TK substrate, and will undergo PET imaging to quantify HSV-1 TK gene expression. Toxicity assessments will occur twice a week for the first 2 weeks and then at scheduled follow-up visits through 60 months. The primary endpoint is toxicity. Secondary endpoints include 1) tumor (radiological) response, 2) local, regional, and distal tumor control, 3) progression-free and overall survival, and 4) quality of life. Exploratory endpoints include 1) intensity, persistence, and biodistribution of HSV-1 TK gene expression, and 2) association of select serum biomarkers with toxicity and tumor response.
- Conditions
- Non-small Cell Lung Cancer Stage I
- Being tested
- Ad5-yCD/mutTKSR39rep-ADP Adenovirus
- Keywords
- lung cancer, adenovirus, gene therapy, SBRT
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Adenoviridae Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ad5-yCD/mutTKSR39rep-ADP AdenovirusBiological
oncolytic adenovirus
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | Nine subjects (3 cohorts, 3 subjects/cohort) with medically inoperable stage I/IIA (T1a - T2b) NSCLC with tumors measuring > 2 to ≤ 5 cm will receive a single intratumoral injection of the oncolytic Ad5-yCD/mutTKSR39rep-ADP adenovirus at one of three dose levels (1 x 1011 vp, 3 x 1011 vp, 1 x 1012 vp). Depending on the location of the target lesion, the adenovirus will be injected either transbronchially (central tumors) or percutaneously under computed tomography (CT)-guidance (peripheral tumors). Two days later, subjects will be administered (orally) a 10 day course of 5-fluorocytosine (5-FC) and valganciclovir (vGCV) prodrug therapy along with 48 Gy (4 fractions of 12 Gy) of SBRT. Prior to and following the adenovirus injection, subjects will be administered [18F]-FHBG, a HSV-1 TK substrate, and will undergo PET imaging to quantify HSV-1 TK gene expression. Receives: Biological: Ad5-yCD/mutTKSR39rep-ADP Adenovirus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Toxicity and maximum tolerated dose
Treatment-related adverse events (CTCAE v4.03)
Measured: 60 days
Secondary outcomes (3)
Tumor response
RECIST
Measured: 3 months to 5 years
Survival
Progression-free and overall
Measured: 3 months to 5 years
Quality of Life
FACT-TOI (Functional Assessment of Cancer Therapy-Trial Outcome Index)
Measured: 3 months to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2017 (estimated)
- Study start13 Jan 2017
- Primary completion31 Dec 2018 (estimated)
- Study completion31 Dec 2022 (estimated)
Why it stopped: No participants were enrolled
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-small Cell Lung Cancer Stage IStudies of the same condition, open and under way.
- 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
- Primary purpose
- Treatment
- Intervention model
- Sequential
- Model description
- Nine subjects (3 cohorts, 3 subjects/cohort)
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Benjamin Movsas, M.D.
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Benjamin Movsas, M.D., Henry Ford Health System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03029871
- Sponsor's protocol ID
- 10835
- Acronym
- NSCLC
- Status last verified
- Aug 2019
- First submitted
- 19 Jan 2017
- Last updated
- 13 Aug 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Trial of Oncolytic Adenovirus-Mediated Cytotoxic Gene Therapy in Combination With Stereotactic Body Radiation Therapy (SBRT) in Clinical Stage 1/11A (T1A-T2B) Non-Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT03029871
- Acronym / sponsor ID
- NSCLC / 10835
- Conditions
- Non-small Cell Lung Cancer Stage I
- Keywords
- lung cancer, adenovirus, gene therapy, SBRT
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: No participants were enrolled
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Benjamin Movsas, M.D.University, hospital or other
- Study start
- 13 Jan 2017 (actual)
- Primary completion
- 31 Dec 2018 (estimated)
- Study completion
- 31 Dec 2022 (estimated)
- First posted
- 24 Jan 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this phase 1 trial is to determine the dose-dependent toxicity and maximum tolerated dose (MTD) of oncolytic adenovirus-mediated cytotoxic gene therapy in combination with SBRT in medically inoperable stage I/IIA (T1A - T2B) NSCLC. To accomplish this objective, 9 subjects will be enrolled in the study. We hypothesize that the combined treatment will demonstrate acceptable toxicity, and that it will be feasible to quantify adenovirus-mediated HSV-1 TK gene expression in the lung by PET. This phase 1 trial will lay the foundation for a follow-up phase 2 trial designed to examine efficacy.
Detailed description
Nine subjects (3 cohorts, 3 subjects/cohort) with medically inoperable stage I/IIA (T1a - T2b) NSCLC with tumors measuring > 2 to ≤ 5 cm will receive a single intratumoral injection of the oncolytic Ad5-yCD/mutTKSR39rep-ADP adenovirus at one of three dose levels (1 x 1011 vp, 3 x 1011 vp, 1 x 1012 vp). Depending on the location of the target lesion, the adenovirus will be injected either transbronchially (central tumors) or percutaneously under computed tomography (CT)-guidance (peripheral tumors). Two days later, subjects will be administered (orally) a 10 day course of 5-fluorocytosine (5-FC) and valganciclovir (vGCV) prodrug therapy along with 48 Gy (4 fractions of 12 Gy) of SBRT. Prior to and following the adenovirus injection, subjects will be administered [18F]-FHBG, a HSV-1 TK substrate, and will undergo PET imaging to quantify HSV-1 TK gene expression. Toxicity assessments will occur twice a week for the first 2 weeks and then at scheduled follow-up visits through 60 months. The primary endpoint is toxicity. Secondary endpoints include 1) tumor (radiological) response, 2) local, regional, and distal tumor control, 3) progression-free and overall survival, and 4) quality of life. Exploratory endpoints include 1) intensity, persistence, and biodistribution of HSV-1 TK gene expression, and 2) association of select serum biomarkers with toxicity and tumor response.
Study design
- Primary purpose
- Treatment
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Nine subjects (3 cohorts, 3 subjects/cohort)
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Biological: Ad5-yCD/mutTKSR39rep-ADP AdenovirusNine subjects (3 cohorts, 3 subjects/cohort) with medically inoperable stage I/IIA (T1a - T2b) NSCLC with tumors measuring > 2 to ≤ 5 cm will receive a single intratumoral injection of the oncolytic Ad5-yCD/mutTKSR39rep-ADP adenovirus at one of three dose levels (1 x 1011 vp, 3 x 1011 vp, 1 x 1012 vp). Depending on the location of the target lesion, the adenovirus will be injected either transbronchially (central tumors) or percutaneously under computed tomography (CT)-guidance (peripheral tumors). Two days later, subjects will be administered (orally) a 10 day course of 5-fluorocytosine (5-FC) and valganciclovir (vGCV) prodrug therapy along with 48 Gy (4 fractions of 12 Gy) of SBRT. Prior to and following the adenovirus injection, subjects will be administered [18F]-FHBG, a HSV-1 TK substrate, and will undergo PET imaging to quantify HSV-1 TK gene expression. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Pathologically (histologically or cytologically) proven diagnosis of NSCLC.
- Clinical stage I/IIA (T1a - T2b; AJCC Staging 7th edition) with a tumor size > 1 cm to ≤ 6 cm in diameter (long axis) based on the following minimum diagnostic workup:
- Note: Subjects may have M0 or MX status (e.g., lung nodules that are being observed). Known M1 disease is excluded. Subjects may have only one target lesion for SBRT.
- Evaluation at lung multi-disciplinary tumor board with recommendation for SBRT within 12 weeks of registration.
- Whole body positron emission tomography (PET/CT) scan within 12 weeks of registration using [18F]-FDG with adequate visualization of the primary tumor and draining lymph node basins in the hilar and mediastinal regions.
Key exclusion criteria (12 listed)
- Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 2 years (e.g., carcinomas in situ of the breast, oral cavity, or cervix are permissible). Subjects with previous lung cancer are permitted if the subject is disease-free for a minimum of 2 years or if this is a solitary recurrence in the lung measuring > 2 cm and ≤ 5 cm after surgery.
- Any known metastatic disease. Subjects may have MX status (e.g., lung nodules that are being observed).
- Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields.
- Prior chemotherapy for the study cancer.
- Plans for the subject to receive other local therapy (including standard fractionated radiotherapy and/or surgery and/or other local ablative therapies) while on this study, except in the case of disease progression.
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 |
|---|---|---|
| Ad5-yCD/mutTKSR39rep-ADP Adenovirusoncolytic adenovirus | Biological | Arm 1 |
Primary outcome
Toxicity and maximum tolerated dose
Time frame: 60 days
Treatment-related adverse events (CTCAE v4.03)
3 secondary outcomes
Tumor response
Time frame: 3 months to 5 years
Survival
Time frame: 3 months to 5 years
Quality of Life
Time frame: 3 months to 5 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2019.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ad5-yCD/mutTKSR39rep-ADP Adenovirus in people with Non-small Cell Lung Cancer Stage I, run by Benjamin Movsas, M.D. 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 18 inclusion and 12 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: withdrawn, as of the sponsor's last update on 13 Aug 2019. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Toxicity and maximum tolerated dose (time frame: 60 days). 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 13 Aug 2019.