Solid TumorPhase 2NCT03544723
Safety and Efficacy of p53 Gene Therapy Combined With Immune Checkpoint Inhibitors in Solid Tumors.
A Phase 2 study testing Ad-p53 in people with Solid Tumor and Lymphoma, run by MultiVir, Inc. at 3 sites in United States.
Trial summary
This is a single arm Phase 2 study of the combination of adenoviral p53 (Ad-p53) gene therapy administered intra-tumorally with approved immune checkpoint inhibitors in patients with recurrent or metastatic cancers. Comparison will be made to historical data. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumor, Lymphoma
- What is being tested?
- Ad-p53
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 3 sitesUnited States
- Study dates
- 1 Oct 2018to 31 Dec 2022
- Phase
- Phase 2
- 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
- Signed informed consent.
- Male or female greater than or equal to 18 years of age (females of childbearing potential must be non-pregnant with a negative pregnancy test and non-lactating). Males and females must use contraception for the duration of the study.
- Primary diagnosis must be histologically confirmed.
- Progression or Recurrence of solid tumors or lymphoma suitable for anti-PD-1/anti-PD-L1 therapy.
- As far as possible, all target lesions utilized for RECIST response determination should be suitable for ultra-sound, CT or endoscopic guided intra-tumoral injection. If all target lesions cannot be treated with Ad-p53, but the patient is otherwise suitable for the study, this should be reviewed with the Sponsor.
- Patients entered on the study must have disease that that is evaluable for response using RECIST 1.1 criteria with a minimum measurable lesion size of the longest axis greater than or equal to 1.0 cm (CT/MRI) or greater than or equal to 2.0 cm (non-helical CT), or nodal shortest diameter greater than or equal to 1.5 cm by CT/MRI.
Show all 24Show fewer
- No brain metastases or treated and stable brain metastases
- ECOG Performance Status 0-1
- Life expectancy greater than or equal to 6 months.
- Adequate bone marrow and hepatic function as evidenced by the following:
- ANC greater than or equal to 1500 cells/mm3
- AST/SGOT and/or ALT/SGPT less than or equal to 3.0 x ULN
- Alkaline phosphatase less than or equal to 5 x ULN
- Platelet count greater than or equal to 100,000 cells/mm3
- Hemoglobin ≥9.0 g/dL
- Creatinine less than 2.0 mg/dL or creatinine clearance greater than or equal to 50 mL/min
- Total bilirubin less than 1.5 x ULN
- Serum albumin greater than or equal to 3.0 g/dL
- Favorable tumor p53 biomarker profile as defined by wild type p53 gene sequence, or less than 20 percent p53 positive tumor cells by immunohistochemistry (IHC), or p53 gene mutations that will not inhibit normal p53 function such as gene deletions, truncations, or frame-shift mutations that result in non-functional p53 tetramerization. Mutant p53 gene profiles should be reviewed with the Sponsor to confirm eligibility.
- Normal troponin blood levels.
- Echo with normal ejection fractions.
- QTcb less than or equal to 470 ms
- Normal lung oxygen saturation by pulse oximeter.
- Coagulation status should be suitable for intra-tumoral injections. Prothrombin Time (PT) less than or equal to 1.5 x ULN (or INR less than or equal to 1.3)*, Partial thromboplastin time (PTT) less than or equal to 1.5 x ULN* *Prolongation in INR, PT, and PTT when the result is from therapeutic anti-coagulation treatment are permitted for patients whose injectable lesions are cutaneous and/or subcutaneous such that direct pressure could be applied in the event of excessive bleeding.
Who cannot join
- History of allergic reactions to any components of the treatments (Ad-p53 or immune checkpoint inhibitors).
- Active alcohol dependence
- Neuropathy of less than or equal to grade 2 CTCAE.
- Except for ongoing treatment with anti-PD-1 or anti-PD-L1 which is permitted (see Inclusion Criterion #4 above), there should be no other antibody-based therapy, targeted small-molecule therapy, hormonal therapy, chemotherapy, radiation, biological or investigational therapy within 14 days of first administration of Study Treatment (C1D1). Subjects with prior cytotoxic or investigational products less than 2 weeks prior to trial treatment might be eligible after discussion between investigator and Sponsor, if toxicities from the prior treatment have been resolved to Grade 1 (NCI CTCAE). If a patient with HNSCC is receiving combination pembrolizumab plus chemotherapy, the first Ad-p53 Study Treatment should be administered 2 weeks following the completion of final chemotherapy treatments and 5 days before their next anti-PD-1/anti-PD-L1 scheduled dose. Ad-p53 intratumoral injections should not be given within 24 hours of immune checkpoint inhibitor infusions.
- Prior additional malignancy within 2 years except for non-melanoma skin cancer, carcinoma in situ of the breast, oral cavity, cervix or other cancers, unless approved by the Sponsor.
- Prior autologous or allogenic organ or tissue transplantation.
Show all 21Show fewer
- Severe, active comorbidity, including any of the following:
- Active clinically serious infection (grade 2 or greater, CTCAE) or requiring intravenous antibiotics at the time of study treatment.
- Thrombotic or embolic event within the last 6 months unless approved by the Sponsor.
- Bleeding or evidence or history of clinically significant bleeding diathesis or coagulopathy within the last 3 months
- Uncontrolled hypertension despite treatment with anti-hypertensive medication (systolic blood pressure less than160 mmHg or diastolic blood pressure less than 100 mmHg)
- Must not have active, known or suspected autoimmune disease or be immunosuppressed
- Known acute or chronic hepatitis B or hepatitis C infection with signs of immunosuppression
- Known significant immunodeficiency due to underlying illness (e.g. HIV/AIDS) and/or immunosuppressive medication including high-dose corticosteroids; HIV patients may be approved by the Sponsor if on treatment with appropriate viral titers.
- Severe bleeding, hemoptysis, gastrointestinal hemorrhage, CNS bleeding, clinically significant hemorrhage or vaginal bleeding during the last 6 months
- Active brain metastases or leptomeningeal metastases are not allowed
- Subjects must not have evidence of autoimmune pneumonitis or inflammatory lung disease on CT scan and chest x-ray. Pneumonitis secondary to radiation scarring is permitted in the absence of dyspnea.
- QTCb less than 470 ms
- Systemic corticosteroid treatment for more than 6 months at doses above 10 mg prednisolone or equivalent before study entry
- Psychological, familial, sociological or geographical or other condition which in the opinion of the investigator would not permit study follow-up or other compliance with the study protocol.
- Subjects may not have target tumors for Ad-p53 injection adjacent to vital structures such as carotid arteries.
Trial locations and contacts
3 sites in 1 country.
United States3 sites, 3 recruiting
- Recruiting
Robert H. Lurie Comprehensive Cancer Center | Northwestern University
Chicago, Illinois, 60611
Stephan Anami, 312-695-2084, stephan.anami@northwestern.edu
Victoria Villaflor, MD
- Recruiting
Rush University Cancer Center
Chicago, Illinois, 60612
Aaron Munoz, 312-563-8756, aaron_munoz@rush.edu
Steffi Leung, 312-942-5183, Steffi_Leung@rush.edu
- Recruiting
Morristown Medical Center
Morristown, New Jersey, 07960
Missak Haigentz, MD, 973-971-7960
Stephanie Beers, RN, 973-971-6283, Stephanie.Beers@atlantichealth.org
About this study
Official title: A Phase 2, Multi-Center, Open Label Study to Evaluate Adenoviral p53 (Ad-p53) in Combination With Immune Checkpoint Inhibitor Therapy in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma and Other Tumors Approved for Anti-PD-1 or Anti-PD-L1 Therapy
This is a single arm Phase 2 study of the combination of adenoviral p53 (Ad-p53) gene therapy administered intra-tumorally with approved immune checkpoint inhibitors in patients with recurrent or metastatic cancers. Comparison will be made to historical data. General safety and efficacy using RECIST 1.1 and Immune-Related Response Criteria as well as ECOG performance will be utilized.
Read the detailed description
This is a Phase 2 study of the combination of Ad-p53 administered intra-tumorally in combination with physician's choice of FDA approved immune checkpoint inhibitor therapy in patients with recurrent or metastatic cancers. This is a safety and efficacy study with a single cohort, consisting of the combination of Ad-p53 and infusions of immune checkpoint inhibitors. Immune checkpoint inhibitor treatments will be administered in accordance with FDA package inserts. Comparison will be made to historical data. General safety and preliminary efficacy will be determined using RECIST 1.1, ECOG status and Immune-Related Response Criteria. Biomarker testing of archival or fresh tissue is performed during the study. Enrollment will be up to 40 patients.
- Conditions
- Solid Tumor, Lymphoma
- Being tested
- Ad-p53
- Keywords
- immune checkpoint inhibitor, anti-PD-1, anti-PD-L1, immune therapy, squamous cell cancer, solid tumor, lymphoma, carcinoma, breast cancer triple negative, cervical cancer, gastric cancer, gastroesophageal junction cancer, esophageal cancer, head and neck squamous cell cancer, hepatocellular cancer, Hodgkin's disease, non-small cell lung cancer, small cell lung cancer, melanoma, merkel cell cancer
- Medical subject headings
- Lymphoma, Neoplasms, Squamous Cell, Carcinoma, Triple Negative Breast Neoplasms, Uterine Cervical Neoplasms, Stomach Neoplasms, Esophageal Neoplasms, Liver Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ad-p53Drug
Also called anti-PD-1/anti-PD-L1, nivolumab, pembrolizumab, atezolizumab
Antineoplastic, Monoclonal Antibody; PD-1/PD-L1 Inhibitors. Immunotherapy. Gene Therapy.
| Study group | Role | What they receive |
|---|---|---|
| Ad-p53 with anti-PD-1/anti-PD-L1 100% of patients | Experimental | Up to 40 patients, all patients treated with intra-tumoral Ad-p53 (dose determined by tumor size) in combination with IV physician's choice of approved immune checkpoint inhibitor Receives: Drug: Ad-p53 |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary efficacy endpoint is objective response rate (ORR)
Objective response rate will be evaluated by RECIST 1.1
Measured: Change in tumor size at the end of Cycle 2 (each cycle is 28 days)
Safety assessments of adverse events per CTCAE
Safety evaluations will tabulate adverse events per CTCAE
Measured: Signed Informed Consent through 30 Days following the final treatment
Secondary outcomes (2)
Preliminary assessment of Duration of Response (DoR) by RECIST 1.1
RECIST 1.1 will be used to determine Duration of Response (DoR)
Measured: Day 1 through end of study, approximately 2 years
Preliminary assessment of progression free survival (PFS) by RECIST 1.1
RECIST 1.1 will be used to determine progression free survival
Measured: Day 1 through end of study, approximately 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2018
- Study start1 Oct 2018
- Primary completion30 Jun 2022 (estimated)
- Study completion31 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid TumorStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Intratumoral Ad-p53 combined with approved immune checkpoint inhibitor
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- MultiVir, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03544723
- Sponsor's protocol ID
- Ad-p53-002
- Status last verified
- Jun 2020
- First submitted
- 9 May 2018
- Last updated
- 9 Jun 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Journal articles and posters, no identifiable data
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Multi-Center, Open Label Study to Evaluate Adenoviral p53 (Ad-p53) in Combination With Immune Checkpoint Inhibitor Therapy in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma and Other Tumors Approved for Anti-PD-1 or Anti-PD-L1 Therapy
- ClinicalTrials.gov ID
- NCT03544723
- Acronym / sponsor ID
- Ad-p53-002
- Conditions
- Solid Tumor, Lymphoma
- Keywords
- immune checkpoint inhibitor, anti-PD-1, anti-PD-L1, immune therapy, squamous cell cancer, solid tumor, lymphoma, carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- MultiVir, Inc.Industry (pharma, biotech, devices)
- Study start
- 1 Oct 2018 (actual)
- Primary completion
- 30 Jun 2022 (estimated)
- Study completion
- 31 Dec 2022 (estimated)
- First posted
- 4 Jun 2018 (actual)
- 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.
This is a single arm Phase 2 study of the combination of adenoviral p53 (Ad-p53) gene therapy administered intra-tumorally with approved immune checkpoint inhibitors in patients with recurrent or metastatic cancers. Comparison will be made to historical data. General safety and efficacy using RECIST 1.1 and Immune-Related Response Criteria as well as ECOG performance will be utilized.
Detailed description
This is a Phase 2 study of the combination of Ad-p53 administered intra-tumorally in combination with physician's choice of FDA approved immune checkpoint inhibitor therapy in patients with recurrent or metastatic cancers. This is a safety and efficacy study with a single cohort, consisting of the combination of Ad-p53 and infusions of immune checkpoint inhibitors. Immune checkpoint inhibitor treatments will be administered in accordance with FDA package inserts. Comparison will be made to historical data. General safety and preliminary efficacy will be determined using RECIST 1.1, ECOG status and Immune-Related Response Criteria. Biomarker testing of archival or fresh tissue is performed during the study. Enrollment will be up to 40 patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Intratumoral Ad-p53 combined with approved immune checkpoint inhibitor
| Arm | Type | Receives |
|---|---|---|
| Ad-p53 with anti-PD-1/anti-PD-L1 100% of patients | Experimental | Drug: Ad-p53Up to 40 patients, all patients treated with intra-tumoral Ad-p53 (dose determined by tumor size) in combination with IV physician's choice of approved immune checkpoint inhibitor |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Signed informed consent.
- Male or female greater than or equal to 18 years of age (females of childbearing potential must be non-pregnant with a negative pregnancy test and non-lactating). Males and females must use contraception for the duration of the study.
- Primary diagnosis must be histologically confirmed.
- Progression or Recurrence of solid tumors or lymphoma suitable for anti-PD-1/anti-PD-L1 therapy.
- As far as possible, all target lesions utilized for RECIST response determination should be suitable for ultra-sound, CT or endoscopic guided intra-tumoral injection. If all target lesions cannot be treated with Ad-p53, but the patient is otherwise suitable for the study, this should be reviewed with the Sponsor.
Key exclusion criteria (21 listed)
- History of allergic reactions to any components of the treatments (Ad-p53 or immune checkpoint inhibitors).
- Active alcohol dependence
- Neuropathy of less than or equal to grade 2 CTCAE.
- Except for ongoing treatment with anti-PD-1 or anti-PD-L1 which is permitted (see Inclusion Criterion #4 above), there should be no other antibody-based therapy, targeted small-molecule therapy, hormonal therapy, chemotherapy, radiation, biological or investigational therapy within 14 days of first administration of Study Treatment (C1D1). Subjects with prior cytotoxic or investigational products less than 2 weeks prior to trial treatment might be eligible after discussion between investigator and Sponsor, if toxicities from the prior treatment have been resolved to Grade 1 (NCI CTCAE). If a patient with HNSCC is receiving combination pembrolizumab plus chemotherapy, the first Ad-p53 Study Treatment should be administered 2 weeks following the completion of final chemotherapy treatments and 5 days before their next anti-PD-1/anti-PD-L1 scheduled dose. Ad-p53 intratumoral injections should not be given within 24 hours of immune checkpoint inhibitor infusions.
- Prior additional malignancy within 2 years except for non-melanoma skin cancer, carcinoma in situ of the breast, oral cavity, cervix or other cancers, unless approved by the Sponsor.
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 |
|---|---|---|
| Ad-p53Also: anti-PD-1/anti-PD-L1, nivolumab, pembrolizumab, atezolizumabAntineoplastic, Monoclonal Antibody; PD-1/PD-L1 Inhibitors. Immunotherapy. Gene Therapy. | Drug | Ad-p53 with anti-PD-1/anti-PD-L1 100% of patients |
Primary outcome
The primary efficacy endpoint is objective response rate (ORR)
Time frame: Change in tumor size at the end of Cycle 2 (each cycle is 28 days)
Objective response rate will be evaluated by RECIST 1.1
Safety assessments of adverse events per CTCAE
Time frame: Signed Informed Consent through 30 Days following the final treatment
Safety evaluations will tabulate adverse events per CTCAE
2 secondary outcomes
Preliminary assessment of Duration of Response (DoR) by RECIST 1.1
Time frame: Day 1 through end of study, approximately 2 years
Preliminary assessment of progression free survival (PFS) by RECIST 1.1
Time frame: Day 1 through end of study, approximately 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2020.
- Individual participant dataSharing planned: No. Journal articles and posters, no identifiable data
Related trials for Solid Tumor
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
Active, not recruitingPhase 3
A Safety and Efficacy Extension Study of Pertuzumab in Patients With Solid Tumors Previously Enrolled in a Hoffmann-La Roche-Sponsored Pertuzumab Clinical Trial
Solid Tumors
RecruitingPhase 1
IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors
Relapsed Solid Tumor Malignancies, Refractory Solid Tumor Malignancies
RecruitingObservational study
Immune Checkpoint Inhibitor Toxicity Risk Prediction in Solid Tumors
Malignant Solid Neoplasm
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.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ad-p53 in people with Solid Tumor and Lymphoma, run by MultiVir, Inc. at 3 sites 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 24 inclusion and 21 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: status not confirmed, as of the sponsor's last update on 9 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Beatha H Sellman, MA (713-668-5684, bsellman@multivir.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary efficacy endpoint is objective response rate (ORR) (time frame: Change in tumor size at the end of Cycle 2 (each cycle is 28 days)). 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 9 Jun 2020.