Last reviewed · How we verify

NCT01218867

CAR T Cell Receptor Immunotherapy Targeting VEGFR2 for Patients With Metastatic Cancer

Terminated Phase 1, PHASE2 Results posted Last updated 10 December 2019
What this trial tests

Phase 1, PHASE2 trial testing Anti-VEGFR2 CAR CD8 plus PBL in Metastatic Cancer in 24 participants. Terminated before completion.

Timeline
10 November 2010
Primary endpoint
3 September 2014
15 December 2015

Quick facts

Lead sponsorNational Cancer Institute (NCI)
PhasePhase 1, PHASE2
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment24
Start date10 November 2010
Primary completion3 September 2014
Estimated completion15 December 2015
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

National Cancer Institute (NCI)

Who can join

Adults 18 to 70, any sex, with Metastatic Cancer or Metastatic Melanoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With a Response to Therapy Primary · 5 years

Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. Progressive disease (PD) is at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment starts or the appearance of one or more new lesions. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to

Complete Response (CR)
GroupValue95% CI
Cohort 1 - 1x10(6) Cells (High Dose IL-2)0
Cohort 2 - 3x10(6) Cells (High Dose IL-2)0
Cohort 3 - 1x10(7) Cells (High Dose IL-2)0
Cohort 4 - 3x10(7) Cells (High Dose IL-2)0
Cohort 5 - 1x10(8) Cells (High Dose IL-2)0
Cohort 6 - 3x10(8) Cells (High Dose IL-2)0
Cohort 7 - 1x10(9) Cells (High Dose IL-2)0
Cohort 8 - 1x10(9) Cells (Low Dose IL-2)0
Cohort 9 - 3x10(9) Cells (Low Dose IL-2)0
Cohort 10 - 1x10(10) Cells (Low Dose IL-2)0
Cohort 11 - 3x10(10) Cells (Low Dose IL-2)0
Partial Response (PR)
GroupValue95% CI
Cohort 1 - 1x10(6) Cells (High Dose IL-2)0
Cohort 2 - 3x10(6) Cells (High Dose IL-2)0
Cohort 3 - 1x10(7) Cells (High Dose IL-2)0
Cohort 4 - 3x10(7) Cells (High Dose IL-2)0
Cohort 5 - 1x10(8) Cells (High Dose IL-2)0
Cohort 6 - 3x10(8) Cells (High Dose IL-2)0
Cohort 7 - 1x10(9) Cells (High Dose IL-2)0
Cohort 8 - 1x10(9) Cells (Low Dose IL-2)0
Cohort 9 - 3x10(9) Cells (Low Dose IL-2)0
Cohort 10 - 1x10(10) Cells (Low Dose IL-2)1
Cohort 11 - 3x10(10) Cells (Low Dose IL-2)0
Progressive Disease (PD)
GroupValue95% CI
Cohort 1 - 1x10(6) Cells (High Dose IL-2)1
Cohort 2 - 3x10(6) Cells (High Dose IL-2)1
Cohort 3 - 1x10(7) Cells (High Dose IL-2)3
Cohort 4 - 3x10(7) Cells (High Dose IL-2)1
Cohort 5 - 1x10(8) Cells (High Dose IL-2)1
Cohort 6 - 3x10(8) Cells (High Dose IL-2)1
Cohort 7 - 1x10(9) Cells (High Dose IL-2)3
Cohort 8 - 1x10(9) Cells (Low Dose IL-2)3
Cohort 9 - 3x10(9) Cells (Low Dose IL-2)3
Cohort 10 - 1x10(10) Cells (Low Dose IL-2)3
Cohort 11 - 3x10(10) Cells (Low Dose IL-2)2
Stable Disease (SD)
GroupValue95% CI
Cohort 1 - 1x10(6) Cells (High Dose IL-2)0
Cohort 2 - 3x10(6) Cells (High Dose IL-2)0
Cohort 3 - 1x10(7) Cells (High Dose IL-2)0
Cohort 4 - 3x10(7) Cells (High Dose IL-2)0
Cohort 5 - 1x10(8) Cells (High Dose IL-2)0
Cohort 6 - 3x10(8) Cells (High Dose IL-2)0
Cohort 7 - 1x10(9) Cells (High Dose IL-2)1
Cohort 8 - 1x10(9) Cells (Low Dose IL-2)0
Cohort 9 - 3x10(9) Cells (Low Dose IL-2)0
Cohort 10 - 1x10(10) Cells (Low Dose IL-2)0
Cohort 11 - 3x10(10) Cells (Low Dose IL-2)0
Number of Participants With Serious and Non-Serious Adverse Events Secondary · Date treatment consent signed to date off study, approximately, 33 months and 25 days

Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v3.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one

GroupValue95% CI
Cohort 1 - 1 x 10(6) Cells (High Dose IL-2)1
Cohort 2 - 3 x 10(6) Cells (High Dose IL-2)1
Cohort 3 - 1 x 10(7) Cells (High Dose IL-2)3
Cohort 4 - 3 x 10(7) Cells (High Dose IL-2)1
Cohort 5 - 1 x 10(8) Cells (High Dose IL-2)1
Cohort 6 - 3 x 10(8) Cells (High Dose IL-2)1
Cohort 7 - 1 x 10(9) Cells (High Dose IL-2)4
Cohort 8 - 1 x 10(9) Cells (Low Dose IL-2)3
Cohort 9 - 3 x 10(9) Cells (Low Dose IL-2)3
Cohort 10 - 1 x 10(10) Cells (Low Dose IL-2)3
Cohort 11 - 3 x 10(10) Cells (Low Dose IL-2)2

Adverse events — posted to ClinicalTrials.gov

Time frame: Date treatment consent signed to date off study, approximately, 33 months and 25 days. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort 1 (1x10(6) Cells (High Dose IL-2)
Serious: 0/1 (0%)
Deaths: 0/1
Cohort 2 (3x10(6) Cells (High Dose IL-2)
Serious: 0/1 (0%)
Deaths: 0/1
Cohort 3 (1x10(7) Cells (High Dose IL-2)
Serious: 1/3 (33%)
Deaths: 0/3
Cohort 4 (3x10(7) Cells (High Dose IL-2)
Serious: 0/1 (0%)
Deaths: 0/1
Cohort 5 (1x10(8) Cells (High Dose IL-2)
Serious: 1/1 (100%)
Deaths: 0/1
Cohort 6 (1x10(8) Cells (High Dose IL-2)
Serious: 0/1 (0%)
Deaths: 0/1
Cohort 7 (1x10(9) Cells (High Dose IL-2)
Serious: 3/4 (75%)
Deaths: 1/4
Cohort 8 (1x10(9) Cells (Low Dose IL-2)
Serious: 0/3 (0%)
Deaths: 0/3
Cohort 9 (3x10(9) Cells (Low Dose IL-2)
Serious: 0/3 (0%)
Deaths: 0/3
Cohort 10 (1x10(10) Cells (Low Dose IL-2)
Serious: 0/4 (0%)
Deaths: 0/4
Cohort 11 (3x10(10) Cells (Low Dose IL-2)
Serious: 0/2 (0%)
Deaths: 0/2

Serious adverse events (8 terms)

ReactionSystemCohort 1 (1x10(6) Cells (H…Cohort 2 (3x10(6) Cells (H…Cohort 3 (1x10(7) Cells (H…Cohort 4 (3x10(7) Cells (H…Cohort 5 (1x10(8) Cells (H…Cohort 6 (1x10(8) Cells (H…Cohort 7 (1x10(9) Cells (H…Cohort 8 (1x10(9) Cells (L…Cohort 9 (3x10(9) Cells (L…Cohort 10 (1x10(10) Cells …Cohort 11 (3x10(10) Cells …
ALT, SGPT (serum glutamic pyruvic transaminase)Metabolism and nutrition disorders
AST, SGOT (serum glutamic oxaloacetic transaminase)Metabolism and nutrition disorders
Bilirubin (hyperbilirubinemia)Metabolism and nutrition disorders
HypoxiaRespiratory, thoracic and mediastinal disorders
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
PainGeneral disorders
InfectionInfections and infestations
Other adverse events (44 terms — click to expand)

ReactionSystemCohort 1 (1x10(6) Cells (H…Cohort 2 (3x10(6) Cells (H…Cohort 3 (1x10(7) Cells (H…Cohort 4 (3x10(7) Cells (H…Cohort 5 (1x10(8) Cells (H…Cohort 6 (1x10(8) Cells (H…Cohort 7 (1x10(9) Cells (H…Cohort 8 (1x10(9) Cells (L…Cohort 9 (3x10(9) Cells (L…Cohort 10 (1x10(10) Cells …Cohort 11 (3x10(10) Cells …
Leukocytes (Total WBC)Blood and lymphatic system disorders
LymphopeniaBlood and lymphatic system disorders
Neutrophils/granulocytes (ANC/AGC)Blood and lymphatic system disorders
PlateletsBlood and lymphatic system disorders
HemoglobinBlood and lymphatic system disorders
InfectionInfections and infestations
Fatigue (asthenia, lethargy, malaise)General disorders
HypotensionCardiac disorders
Febrile neutropeniaInfections and infestations
Supraventricular and nodal arrhythmiaCardiac disorders
Albumin, serum-low (hypoalbuminemia)Metabolism and nutrition disorders
Dyspnea (shortness of breath)Respiratory, thoracic and mediastinal disorders
Phosphate, serum-low (hypophosphatemia)Metabolism and nutrition disorders
Alkaline phosphataseMetabolism and nutrition disorders
Hemorrhage, pulmonary/upper respiratoryRespiratory, thoracic and mediastinal disorders
CreatinineMetabolism and nutrition disorders
PainGeneral disorders
Acute vascular leak syndromeVascular disorders
HypoxiaRespiratory, thoracic and mediastinal disorders
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)General disorders
PTT (Partial Thromboplstin Time)Blood and lymphatic system disorders
ConfusionNervous system disorders
DehydrationGastrointestinal disorders
NauseaGastrointestinal disorders
Liver dysfunction/failure (clinical)Hepatobiliary disorders
Calcium, serum-low (hypocalcemia)Metabolism and nutrition disorders
Potassium, serum-low (hypokalemia)Metabolism and nutrition disorders
Psychosis (hallucinations/delusions)Nervous system disorders
Hearing: patients with/without baseline audiogram and enrolled in a monitoring programEar and labyrinth disorders
ConstipationGastrointestinal disorders
Mucositis/stomatitis (clinical exam)Gastrointestinal disorders
Hemorrhage, GURenal and urinary disorders
ALT, SGPT (serum glutamic pyruvic transaminase)Metabolism and nutrition disorders
AST, SGOT (serum glutamic oxaloacetic transaminase)Metabolism and nutrition disorders
Uric acid, serum-high (hyperuricemia)Metabolism and nutrition disorders
Somnolence/depressed level of consciousnessNervous system disorders
Ocular/Visual-Other (vision changes)Eye disorders
Renal failureRenal and urinary disorders
Syndromes - Other (hemaphogocytic syndrome)General disorders
Syncope (fainting)Nervous system disorders

Most-reported serious reactions: ALT, SGPT (serum glutamic pyruvic transaminase), AST, SGOT (serum glutamic oxaloacetic transaminase), Bilirubin (hyperbilirubinemia), Hypoxia, Nausea, Vomiting, Pain, Infection.

Data from ClinicalTrials.gov NCT01218867 adverse events section.

Sponsor's own description

Background: The National Cancer Institute (NCI) Surgery Branch has developed an experimental therapy for treating patients metastatic cancer that involves taking white blood cells from the patient, growing them in the laboratory in large numbers, genetically modifying these specific cells with a type of virus (retrovirus) to attack only the tumor cells, and then giving the cells back to the patient. This type of therapy is called gene transfer. In this protocol, we are modifying the patient s white blood cells with a retrovirus that has the gene for anti-vascular endothelial growth factor receptor (VEGFR2) incorporated in the retrovirus. Objectives: \- To determine a safe number of these cells to infuse and to see the safety and effectiveness of cell therapy using anti-VEGFR2 gene modified tumor white blood cells to treat recurrent or relapsed cancer. Eligibility: \- Individuals greater than or equal to 18 years of age and less than or equal to 70 years of age who have been diagnosed with metastatic cancer that has not responded to or has relapsed after standard treatment. Design: * Work up stage: Patients will be seen as an outpatient at the National Institutes of Health (NIH) clinical Center and undergo a history and physical examination, scans, x-rays, lab tests, and other tests as needed * Leukapheresis: If the patients meet all of the requirements for the study they will undergo leukapheresis to obtain white blood cells to make the anti-VEGFR2 cells. {Leukapheresis is a common procedure which removes only the white blood cells from the patient.} * Treatment: Once their cells have grown the patients will be admitted to the hospital for the conditioning chemotherapy, the anti-VEGFR2 cells and aldesleukin. They will stay in the hospital for about4 weeks for the treatment. * Follow up: Patients will return to the clinic for a physical exam, review of side effects, lab tests, and scans about every 1-3 months for the first year, and then every 6 months to 1 year as long as their tumors are shrinking. Follow up visits will take up to 2 days.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Enhancing cancer immunotherapy using antiangiogenics: opportunities and challenges.
    Fukumura D, Kloepper J, Amoozgar Z, Duda DG, et al · · 2018 · cited 1560× · PMID 29508855 · DOI 10.1038/nrclinonc.2018.29
  2. Driving CAR T-cells forward.
    Jackson HJ, Rafiq S, Brentjens RJ. · · 2016 · cited 457× · PMID 27000958 · DOI 10.1038/nrclinonc.2016.36
  3. CAR T cells in solid tumors: challenges and opportunities.
    Marofi F, Motavalli R, Safonov VA, Thangavelu L, et al · · 2021 · cited 394× · PMID 33494834 · DOI 10.1186/s13287-020-02128-1
  4. CAR-T cells: the long and winding road to solid tumors.
    D'Aloia MM, Zizzari IG, Sacchetti B, Pierelli L, et al · · 2018 · cited 311× · PMID 29449531 · DOI 10.1038/s41419-018-0278-6
  5. CAR T Cell Therapy for Solid Tumors: Bright Future or Dark Reality?
    Wagner J, Wickman E, DeRenzo C, Gottschalk S. · · 2020 · cited 284× · PMID 32979309 · DOI 10.1016/j.ymthe.2020.09.015
  6. Beyond conventional immune-checkpoint inhibition - novel immunotherapies for renal cell carcinoma.
    Braun DA, Bakouny Z, Hirsch L, Flippot R, et al · · 2021 · cited 263× · PMID 33437048 · DOI 10.1038/s41571-020-00455-z
  7. CAR-T Cells Hit the Tumor Microenvironment: Strategies to Overcome Tumor Escape.
    Rodriguez-Garcia A, Palazon A, Noguera-Ortega E, Powell DJ, et al · · 2020 · cited 225× · PMID 32625204 · DOI 10.3389/fimmu.2020.01109
  8. Driving gene-engineered T cell immunotherapy of cancer.
    Johnson LA, June CH. · · 2017 · cited 211× · PMID 28025979 · DOI 10.1038/cr.2016.154

Verify or expand the search:

Other recruiting trials for Metastatic Cancer

Currently open trials in the same condition.

Other National Cancer Institute (NCI) trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT01218867.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing