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Metastatic Non-small Cell Lung CancerPhase 2STOMPNCT03004183

SBRT and Oncolytic Virus Therapy Before Pembrolizumab for Metastatic TNBC and NSCLC

A Phase 2 study testing ADV/HSV-tk, Valacyclovir and SBRT in people with Metastatic Non-small Cell Lung Cancer and Metastatic Triple-negative Breast Cancer, run by The Methodist Hospital Research Institute at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This is a Phase II trial to determine the efficacy and safety of stereotactic body radiation therapy (SBRT) and in situ oncolytic virus therapy used as a window of opportunity treatment before pembrolizumab in patients with metastatic triple negative breast cancer (TNBC) and metastatic non-small cell lung cancer… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
ADV/HSV-tk, Valacyclovir and SBRT
Could I receive a placebo?
No, everyone receives an active treatment
How many people
57 participants
Where
1 siteUnited States
Study dates
1 Jul 2017to 9 Jan 2024
Phase
Phase 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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Willing and able to provide written informed consent/assent for the trial.
  • Male or female aged ≥18 years on the day of informed consent signing.
  • Histologically confirmed locally advanced or metastatic TNBC that has relapsed on or is refractory to standard of care therapy OR histologically or cytologically confirmed metastatic NSCLC that is immunotherapy and chemotherapy naïve or previously treated with 1 cycle of platinum-containing chemotherapy. Epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) mutation-negative NSCLC patients and NSCLC patients with EGFR or ALK genomic tumor aberrations that have failed FDA-approved targeted therapy for these aberrations will be eligible for enrollment in the study.
  • Measurable disease based on RECIST 1.1, a target lesion of suitable diameter (at least 1 cm) for SBRT, and a non-target lesion (visceral metastatic lesion) at least 1 cm in diameter for abscopal effect evaluation.
  • Willing to provide biopsy tissues as required by the study.
  • Eastern Cooperative Oncology Group performance status of 0 or 1.
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  • Adequate organ function as defined by the following laboratory values:
  • Absolute neutrophil count ≥1,500/µL (without granulocyte colony stimulating factor support within 14 days of assessment)
  • Platelets ≥100,000/µL
  • Hemoglobin ≥8 g/dL or ≥5.6 mmol/L without transfusion or erythropoietin dependency (within 7 days of assessment)
  • White blood cell count >2,500/µL and <15,000/µL
  • Lymphocyte count ≥500/µL
  • Serum creatinine <2 X upper limit of normal (ULN)
  • Serum total bilirubin ≤1.0 X ULN (Subjects with known Gilbert's disease who have serum bilirubin level ≤3 X ULN may be enrolled)
  • Asparate transaminase and alanine transaminase ≤2.5 X ULN with normal alkaline phosphatase (≤5 X ULN for subjects with liver metastases) OR ≤1.5 X ULN in conjunction with alkaline phosphatase >2.5 X ULN
  • Albumin >2.5 mg/dL
  • International normalized ratio or prothrombin time (PT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or activated partial thromboplastin time (aPTT) is within therapeutic range of intended use of anticoagulants
  • aPTT ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
  • Life expectancy ≥ 6 months.
  • ≥ 4 weeks since any major surgery, completion of radiation therapy, or completion of all prior systemic anticancer therapy (adequately recovered from the acute toxicities of any prior therapy).
  • Female subjects of childbearing potential should have a negative serum pregnancy (beta-human chorionic gonadotropin) within 7 days prior to receiving the first dose of the trial treatment and should not be lactating.
  • Female subjects of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study therapy.
  • Male subjects of childbearing potential must agree to use an adequate method of contraception for the course of the study through 120 days after the last dose of study therapy.

Who cannot join

  • Unwilling or unable to comply with the study protocol.
  • Subjects for who bone metastases are the only available non-target lesions for abscopal effect evaluation.
  • Subjects with tumors for which SBRT is not considered appropriate standard therapy. This includes subjects with target lesions less than 1 cm in diameter and those with large central lung lesions.
  • Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of trial treatment.
  • 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.
  • Known history of active tuberculosis (Bacillus Tuberculosis).
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  • Known or suspected hypersensitivity to pembrolizumab or any of its excipients or any component of the proposed regimen (gene vector/valacyclovir).
  • Known gallbladder or bile duct disease (i.e., infection or cholecystitis) or acute or chronic pancreatitis.
  • Eastern Cooperative Oncology Group performance status of ≥2 or oxygen dependence (e.g., advanced chronic obstructive pulmonary disease).
  • Inability to swallow food or any condition of the upper gastrointestinal tract that precludes administration of oral medications (valacyclovir).
  • Congestive heart failure: New York Association class III or IV heart failure or unstable angina.
  • Sustained or clinically significant cardiac arrhythmias including sustained ventricular tachycardia, ventricular fibrillation, clinically significant bradycardia, advanced heart block (Mobitz II or higher atrioventricular nodal block), prolonged corrected QT interval (longer than 470 milliseconds), or history of acute myocardial infarction.
  • Concomitant disease(s) that could prolong QT such as autonomic neuropathy (caused by diabetes or Parkinson's disease), human immunodeficiency virus (HIV), cirrhosis, uncontrolled hypothyroidism, or cardiac failure.
  • History of syncope or family history of idiopathic sudden death.
  • Targeted small molecule therapy or monoclonal antibody or radiation therapy within 3 weeks prior to study Day 0 or has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
  • Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
  • Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
  • Known active central nervous system metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability.
  • Active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). 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.
  • History of (non-infectious) pneumonitis that required steroids or current pneumonitis.
  • Active infection requiring systemic therapy.
  • 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.
  • Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Pregnant or breastfeeding, expecting to conceive or father children within the projected duration of the trial, starting with the prescreening or screening visit through 120 days after the last dose of trial treatment, or is unwilling to practice an effective method of birth control. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to administration of trial treatment.
  • Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent (TNBC cohort only).
  • Prior treatment with immunomodulatory therapy or immunotherapy (TNBC cohort only).
  • Prior treatment with gene vector therapy.
  • Received prior systemic cytotoxic chemotherapy for metastatic disease (NSCLC cohort).
  • Known history of HIV (HIV 1/2 antibodies).
  • History of liver disease such as cirrhosis or known active hepatitis B (e.g., hepatitis B surface antigen reactive) or hepatitis C (e.g., hepatitis C virus RNA [qualitative] is detected).
  • History of or current alcohol misuse/abuse within the past 12 months.
  • Major surgery within 4 weeks prior to study enrollment.
  • Received a live vaccine within 30 days of planned start of trial therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines and are not allowed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Houston Methodist Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Phase II Window of Opportunity Trial of Stereotactic Body Radiation Therapy and In Situ Oncolytic Virus Therapy in Metastatic Triple Negative Breast Cancer and Metastatic Non-Small Cell Lung Cancer Followed by Pembrolizumab

This is a Phase II trial to determine the efficacy and safety of stereotactic body radiation therapy (SBRT) and in situ oncolytic virus therapy used as a window of opportunity treatment before pembrolizumab in patients with metastatic triple negative breast cancer (TNBC) and metastatic non-small cell lung cancer (NSCLC). In situ oncolytic virus therapy will consist of adenovirus-mediated expression of herpes simplex virus thymidine kinase (ADV/HSV-tk) plus valacyclovir therapy.

Read the detailed description

This is a Phase II trial to determine the efficacy and safety of stereotactic body radiation therapy (SBRT) and in situ oncolytic virus therapy used as a window of opportunity treatment before pembrolizumab in patients with metastatic triple negative breast cancer (TNBC) and metastatic non-small cell lung cancer (NSCLC). In situ oncolytic virus therapy will consist of adenovirus-mediated expression of herpes simplex virus thymidine kinase (ADV/HSV-tk) plus valacyclovir. Male and female patients aged ≥ 18 years with histologically confirmed locally advanced or metastatic TNBC that has relapsed on or is refractory to 1 or more lines of standard of care therapy or histologically or cytologically confirmed metastatic NSCLC that is immunotherapy and chemotherapy naïve or previously treated with 1 cycle of platinum-containing chemotherapy are eligible to participate in the study. ADV/HSV-tk (5 x 1011 viral particles) in a 2-mL total volume will be injected intratumorally on Day 0 of the study. Valacyclovir will be orally administered at a dose of 2 g three times daily for 14 days. Valacyclovir treatment will be administered 24 hours after the gene vector injection from Day 1 to Day 15 of the study. SBRT of 30 gray (Gy; 6 Gy X 5 fractions) will be administered over 2 weeks from Day 2 to Day 16 of the study. Pembrolizumab (200 mg) will be administered intravenously over 30 minutes every 3 weeks starting on Day 17 of the study and continuing until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. The primary endpoint will be the objective response rate of ADV/HSV-tk + valacyclovir therapy in combination with SBRT used as a window of opportunity treatment before pembrolizumab in patients with metastatic TNBC and metastatic NSCLC. RECIST 1.1 will be used to assess treatment response. Secondary endpoints will include a) clinical benefit rate; b) duration of response; c) overall survival and progression-free survival rates; d) toxicity (toxicity will be defined as any treatment-related death or any ≥ grade 3 toxicity excluding alopecia and constitutional symptoms as assessed by the NCI CTCAE v4.03); and e) antitumor activity of ADV/HSV-tk plus valacyclovir therapy in combination with SBRT used as a window of opportunity treatment before pembrolizumab.

Being tested
ADV/HSV-tk, Valacyclovir, SBRT, Pembrolizumab
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Triple Negative Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ADV/HSV-tkBiological

    Replication-defective recombinant adenovirus vector

  • ValacyclovirDrug

    Also called valacyclovir hydrochloride

    Prodrug of the antiviral drug acyclovir

  • SBRTRadiation

    Low-dose SBRT

  • PembrolizumabDrug

    Also called Keytruda

    Humanized immunoglobulin G4 anti-programmed death-1 (PD-1) monoclonal antibody

Study groups in NCT03004183
Study groupRoleWhat they receive
Single armExperimentalADV/HSV-tk (5 x 1011 virus particles) in a 2-mL total volume will be injected intratumorally on Day 0. Valacyclovir will be orally administered at a dose of 2 g three times daily for 14 days from Day 1 to Day 15. SBRT of 30 Gy (6 Gy X 5 fractions) will be administered over 2 weeks from Day 2 to Day 16. Pembrolizumab (200 mg) will be administered intravenously over 30 minutes every 3 weeks starting on Day 17 and continuing until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
Receives: Biological: ADV/HSV-tk; Drug: Valacyclovir; Radiation: SBRT; Drug: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate

    The objective response rate (ORR) of ADV/HSV-tk plus (+) valacyclovir therapy in combination with SBRT used as a window of opportunity treatment before pembrolizumab in patients with metastatic TNBC and metastatic NSCLC. Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 will be used to assess treatment response. Modified immune-related response criteria (irRC; derived from RECIST 1.1) will also be documented.

    Measured: 30 days after the last dose of pembrolizumab until disease progression, initiating a non-study cancer treatment, withdrawing consent, or becoming lost to follow-up. Median duration of follow-up was 8.3 months (95% CI 3.0-10.1 months).

Secondary outcomes (6)

  1. Duration of Response

    Duration of response to ADV/HSV-tk plus valacyclovir therapy in combination with SBRT followed by pembrolizumab

    Measured: 30 days after the last dose of pembrolizumab until disease progression, initiating a non-study cancer treatment, withdrawing consent, or becoming lost to follow-up. Median duration of follow-up was 8.3 months (95% CI 3.0-10.1 months).

  2. Overall Survival Rate

    Overall survival (OS) rate in subjects receiving ADV/HSV-tk plus valacyclovir therapy in combination with SBRT followed by pembrolizumab. OS is the time (measured in months) from intratumoral viral injection to death or last date of contact.

    Measured: After confirmed disease progression or starts a new therapy, the subject moves into the Survival Follow-up to be contacted every 12 weeks to assess for survival status until death, withdrawal, or end of study. Median duration of follow-up was 8.3 months.

  3. Number of Participants With Treatment-related Adverse Events

    To document the toxicities associated with ADV/HSV-tk + valacyclovir therapy in combination with SBRT used as a window of opportunity treatment before pembrolizumab in patients with metastatic TNBC and metastatic NSCLC. Toxicity will be defined as the number of participants with any treatment-related death or any ≥ Grade 3 hematological toxicity excluding alopecia and constitutional symptoms, as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03.

    Measured: Adverse Events (AEs) and Serious Adverse Events (SAEs) will be captured from the time of informed consent signing up to 30 days after the final dose of pembrolizumab, (up to 24 months of treatment for patients without disease progression).

  4. Antitumor Activity

    Measure the antitumor activity as assessed by RECIST 1.1. Modified immune-related response criteria will also be documented.

    Measured: 30 days after the last dose of pembrolizumab

  5. Clinical Benefit Rate

    Clinical benefit rate of ADV/HSV-tk plus valacyclovir therapy in combination with SBRT followed by pembrolizumab

    Measured: 30 days after the last dose of pembrolizumab until disease progression, initiating a non-study cancer treatment, withdrawing consent, or becoming lost to follow-up. Median duration of follow-up was 8.3 months (95% CI 3.0-10.1 months).

  6. Progression-free Survival in Months

    To determine the progression-free survival (PFS) of ADV/HSV-tk + valacyclovir therapy in combination with SBRT used as a window of opportunity treatment before pembrolizumab in patients with metastatic TNBC and metastatic NSCLC as measured in months and defined the number of months a patient remains free from disease progression.

    Measured: 30 days after the last dose of pembrolizumab until disease progression, initiating a non-study cancer treatment, withdrawing consent, or becoming lost to follow-up.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Dec 2016 (estimated)
  2. Study start1 Jul 2017
  3. Primary completion22 Jul 2022
  4. Study completion9 Jan 2024

Resources

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
57 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03004183
Sponsor's protocol ID
Pro00015649
Acronym
STOMP
Status last verified
Aug 2024
First submitted
20 Dec 2016
Last updated
15 Oct 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Data and materials on human subjects will be shared with other eligible investigators through appropriate means in accordance with the NIH policy on Sharing Research Data (NIH Guide, February 26, 2003). Data will be also shared with the funding agency and regulatory agencies as required. Data will be shared with other investigators within the limits of HIPAA and other patient confidentiality requirements. This will generally require removal of all patient identifiers for all source documents and the use of arbitrarily assigned one-way identifiers. In some cases, requestors will be asked to sign a formal data sharing agreement that will provide for a commitment to use data only for research purposes and not to identify individuals, keep the data secure, and destroy or return data after analyses are complete. Prior approval will be obtained from collaborating investigators, research sponsors, and/or other stake-holders before sharing if proprietary information or products are involved.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ADV/HSV-tk, Valacyclovir and SBRT in people with Metastatic Non-small Cell Lung Cancer and Metastatic Triple-negative Breast Cancer, run by The Methodist Hospital Research Institute 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 23 inclusion and 33 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: finished, as of the sponsor's last update on 15 Oct 2024. 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 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 25 Jan 2023). 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?

Objective Response Rate (time frame: 30 days after the last dose of pembrolizumab until disease progression, initiating a non-study cancer treatment, withdrawing consent, or becoming lost to follow-up. Median duration of follow-up was 8.3 months (95% CI 3.0-10.1 months).). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03004183.

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 15 Oct 2024.

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