NCT03544723

Brief 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. General safety and efficacy using RECIST 1.1 and Immune-Related Response Criteria as well as ECOG performance will be utilized.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
40

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Oct 2018

Typical duration for phase_2

Geographic Reach
1 country

3 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 9, 2018

Completed
26 days until next milestone

First Posted

Study publicly available on registry

June 4, 2018

Completed
4 months until next milestone

Study Start

First participant enrolled

October 1, 2018

Completed
3.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2022

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2022

Completed
Last Updated

June 9, 2020

Status Verified

June 1, 2020

Enrollment Period

3.7 years

First QC Date

May 9, 2018

Last Update Submit

June 5, 2020

Conditions

Solid TumorLymphoma

Keywords

immune checkpoint inhibitoranti-PD-1anti-PD-L1immune therapysquamous cell cancersolid tumorlymphomacarcinomabreast cancer triple negativecervical cancergastric cancergastroesophageal junction canceresophageal cancerhead and neck squamous cell cancerhepatocellular cancerHodgkin's diseasenon-small cell lung cancersmall cell lung cancermelanomamerkel cell cancerMSI-H/dMMRrenal cell carcinomaurothelial carcinomagene therapyp53 tumor suppressor

Outcome Measures

Primary Outcomes (2)

  • The primary efficacy endpoint is objective response rate (ORR)

    Objective response rate will be evaluated by RECIST 1.1

    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

    Signed Informed Consent through 30 Days following the final treatment

Secondary Outcomes (2)

  • Preliminary assessment of Duration of Response (DoR) by RECIST 1.1

    Day 1 through end of study, approximately 2 years

  • Preliminary assessment of progression free survival (PFS) by RECIST 1.1

    Day 1 through end of study, approximately 2 years

Study Arms (1)

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

Drug: Ad-p53

Interventions

Ad-p53DRUG

Antineoplastic, Monoclonal Antibody; PD-1/PD-L1 Inhibitors. Immunotherapy. Gene Therapy.

Also known as: anti-PD-1/anti-PD-L1, nivolumab, pembrolizumab, atezolizumab, durvalumab
Ad-p53 with anti-PD-1/anti-PD-L1 100% of patients

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.
  • 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
  • +9 more criteria

You may not qualify if:

  • 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.
  • 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.
  • 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
  • +5 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Robert H. Lurie Comprehensive Cancer Center | Northwestern University

Chicago, Illinois, 60611, United States

RECRUITING

Rush University Cancer Center

Chicago, Illinois, 60612, United States

RECRUITING

Morristown Medical Center

Morristown, New Jersey, 07960, United States

RECRUITING

MeSH Terms

Conditions

LymphomaNeoplasms, Squamous CellCarcinomaTriple Negative Breast NeoplasmsUterine Cervical NeoplasmsStomach NeoplasmsEsophageal NeoplasmsLiver NeoplasmsHodgkin DiseaseCarcinoma, Non-Small-Cell LungSmall Cell Lung CarcinomaMelanomaCarcinoma, Merkel CellCarcinoma, Renal CellCarcinoma, Transitional Cell

Interventions

advexinNivolumabpembrolizumabatezolizumabdurvalumab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesNeoplasms, Glandular and EpithelialBreast NeoplasmsNeoplasms by SiteBreast DiseasesSkin DiseasesSkin and Connective Tissue DiseasesUterine NeoplasmsGenital Neoplasms, FemaleUrogenital NeoplasmsUterine Cervical DiseasesUterine DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital DiseasesGastrointestinal NeoplasmsDigestive System NeoplasmsDigestive System DiseasesGastrointestinal DiseasesStomach DiseasesHead and Neck NeoplasmsEsophageal DiseasesLiver DiseasesCarcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsLung DiseasesRespiratory Tract DiseasesNeuroendocrine TumorsNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms, Nerve TissueNevi and MelanomasSkin NeoplasmsPolyomavirus InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsCarcinoma, NeuroendocrineAdenocarcinomaKidney NeoplasmsUrologic NeoplasmsKidney DiseasesUrologic DiseasesMale Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Central Study Contacts

Beatha H Sellman, MA

CONTACT

713-668-5684bsellman@multivir.com

Kerstin B Menander, MD PhD

CONTACT

713-665-9058kmenander@multivir.com

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Model Details: Intratumoral Ad-p53 combined with approved immune checkpoint inhibitor
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 9, 2018

First Posted

June 4, 2018

Study Start

October 1, 2018

Primary Completion

June 30, 2022

Study Completion

December 31, 2022

Last Updated

June 9, 2020

Record last verified: 2020-06

Data Sharing

IPD Sharing
Will not share

Journal articles and posters, no identifiable data

Locations

US(3)