A Phase I Trial of Weekly Indenoisoquinoline LMP400 in Adults With Relapsed Solid Tumors and Lymphomas View Homepage


Ontology type: schema:MedicalStudy     


Clinical Trial Info

YEARS

2013-2017

ABSTRACT

Background: - Indenoisoquinoline LMP400 is an experimental cancer treatment drug. It damages DNA in tumor cells. Tumor cells with damaged DNA may die, resulting in cell death. Researchers want to see if this drug is a safe and effective treatment for solid tumors and lymphomas that have not responded to earlier treatment. Objectives: - To see if Indenoisoquinoline LMP400 is a safe and effective treatment for advanced solid tumors or lymphomas. Eligibility: - Individuals at least 18 years of age who have solid tumors or lymphomas that have not responded to treatment. Design: - Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Tumor samples may also be collected. The size and location of the tumors will be determined with imaging studies. - Indenoisoquinoline LMP400 is given in a 28-day cycle. Participants will receive the drug by intravenous infusion on days 1, 8, and 15 of each cycle, followed by a break of 13 days without the drug. - Treatment will be monitored with frequent blood tests and imaging studies. Tumor samples will be optional. - Participants will continue their cycles of treatment as long as the cancer does not grow and there are no severe side effects. Detailed Description Background: - Indenoisoquinolines are non-camptothecin topoisomerase (Top1) inhibitors that form stable DNA-Top1 cleavage-complexes, have a preference for unique DNA cleavage sites, and are active against camptothecin-resistant cell lines. Unlike camptothecins, indenoisoquinolines are chemically stable and active in cells that over-express ATP-binding cassette (ABC) transporters ABCG2 and multidrug resistance (MDR-1). Top1 inhibitors are potent anticancer agents because stabilizing cleavage complex formation induces replication-and transcription-mediated DNA damage and delays DNA repair, leading to apoptosis. Preclinical and clinical data indicate that baseline tumor levels of Top1 correlate strongly with ability to respond to Top1 inhibitor therapy. - A first-in-human Phase I study conducted at the NCI of the indenoisoquinoline LMP400 (NSC 743400) on a QD x 5 q28 schedule in patients with refractory solid tumors and lymphomas (10-C-0056) established that this agent is well tolerated. LMP400 shows linear pharmacokinetics with evidence of drug accumulation following 5 days of dosing. We hypothesize that weekly dosing (days 1, 8, 15 q28-day cycle) will increase LMP400 peak levels and exposures, improving clinical activity and safety. Primary Objectives: - To establish the safety and tolerability of weekly (days 1, 8, 15 q28-day cycle) LMP400 in patients with refractory solid tumors and lymphomas. - To establish the maximum tolerated dose (MTD) of weekly LMP400 in patients with refractory solid tumors and lymphomas. - To evaluate the pharmacokinetic profile of weekly LMP400. Secondary Objectives: - Evaluate the level of Top1 in tumor biopsies pre- and post- administration of LMP400. - Evaluate the effect of LMP400 on markers of DNA damage and apoptosis, such as >=H2AX and caspase 3, in tumor biopsies pre- and post- LMP400 administration. Eligibility: -Patients with histologically confirmed metastatic solid tumors and lymphomas; adequate organ function. Study Design: - This is an open-label Phase I trial evaluating weekly administration of LMP400, on days 1, 8, and 15, in 28-day cycles. - Starting dose is based on the MTD determined from the QD x 5, q28 day schedule currently being evaluated. The study will follow a 3 plus 3 design. - Once the MTD is established, 10 additional patients will be enrolled at the MTD to further define the pharmacokinetics and evaluate effect of study drug on DNA damage and apoptosis. More... »

URL

https://clinicaltrials.gov/show/NCT01794104

Related SciGraph Publications

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/3164", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "type": "DefinedTerm"
      }
    ], 
    "description": "Background: - Indenoisoquinoline LMP400 is an experimental cancer treatment drug. It damages DNA in tumor cells. Tumor cells with damaged DNA may die, resulting in cell death. Researchers want to see if this drug is a safe and effective treatment for solid tumors and lymphomas that have not responded to earlier treatment. Objectives: - To see if Indenoisoquinoline LMP400 is a safe and effective treatment for advanced solid tumors or lymphomas. Eligibility: - Individuals at least 18 years of age who have solid tumors or lymphomas that have not responded to treatment. Design: - Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Tumor samples may also be collected. The size and location of the tumors will be determined with imaging studies. - Indenoisoquinoline LMP400 is given in a 28-day cycle. Participants will receive the drug by intravenous infusion on days 1, 8, and 15 of each cycle, followed by a break of 13 days without the drug. - Treatment will be monitored with frequent blood tests and imaging studies. Tumor samples will be optional. - Participants will continue their cycles of treatment as long as the cancer does not grow and there are no severe side effects.\n\nDetailed Description\nBackground: - Indenoisoquinolines are non-camptothecin topoisomerase (Top1) inhibitors that form stable DNA-Top1 cleavage-complexes, have a preference for unique DNA cleavage sites, and are active against camptothecin-resistant cell lines. Unlike camptothecins, indenoisoquinolines are chemically stable and active in cells that over-express ATP-binding cassette (ABC) transporters ABCG2 and multidrug resistance (MDR-1). Top1 inhibitors are potent anticancer agents because stabilizing cleavage complex formation induces replication-and transcription-mediated DNA damage and delays DNA repair, leading to apoptosis. Preclinical and clinical data indicate that baseline tumor levels of Top1 correlate strongly with ability to respond to Top1 inhibitor therapy. - A first-in-human Phase I study conducted at the NCI of the indenoisoquinoline LMP400 (NSC 743400) on a QD x 5 q28 schedule in patients with refractory solid tumors and lymphomas (10-C-0056) established that this agent is well tolerated. LMP400 shows linear pharmacokinetics with evidence of drug accumulation following 5 days of dosing. We hypothesize that weekly dosing (days 1, 8, 15 q28-day cycle) will increase LMP400 peak levels and exposures, improving clinical activity and safety. Primary Objectives: - To establish the safety and tolerability of weekly (days 1, 8, 15 q28-day cycle) LMP400 in patients with refractory solid tumors and lymphomas. - To establish the maximum tolerated dose (MTD) of weekly LMP400 in patients with refractory solid tumors and lymphomas. - To evaluate the pharmacokinetic profile of weekly LMP400. Secondary Objectives: - Evaluate the level of Top1 in tumor biopsies pre- and post- administration of LMP400. - Evaluate the effect of LMP400 on markers of DNA damage and apoptosis, such as >=H2AX and caspase 3, in tumor biopsies pre- and post- LMP400 administration. Eligibility: -Patients with histologically confirmed metastatic solid tumors and lymphomas; adequate organ function. Study Design: - This is an open-label Phase I trial evaluating weekly administration of LMP400, on days 1, 8, and 15, in 28-day cycles. - Starting dose is based on the MTD determined from the QD x 5, q28 day schedule currently being evaluated. The study will follow a 3 plus 3 design. - Once the MTD is established, 10 additional patients will be enrolled at the MTD to further define the pharmacokinetics and evaluate effect of study drug on DNA damage and apoptosis.", 
    "endDate": "2017-10-01T00:00:00Z", 
    "id": "sg:clinicaltrial.NCT01794104", 
    "keywords": [
      "Phase I trial", 
      "indenoisoquinolines", 
      "solid tumor", 
      "cancer treatment", 
      "damage DNA", 
      "tumor cell", 
      "damaged DNA", 
      "cell death", 
      "drug", 
      "safe and effective treatment", 
      "lymphoma", 
      "advanced solid tumor", 
      "eligibility", 
      "individual", 
      "age", 
      "physical exam", 
      "medical history", 
      "blood", 
      "urine sample", 
      "tumor sample", 
      "location", 
      "Neoplasm", 
      "imaging study", 
      "cycle", 
      "intravenous infusion", 
      "severe side effect", 
      "topoisomerase", 
      "Top1", 
      "inhibitor", 
      "cleavage", 
      "preference", 
      "cleavage site", 
      "resistant cell line", 
      "camptothecin", 
      "cassette", 
      "ATP-binding cassette", 
      "ATP binding", 
      "Multiple Drug Resistance", 
      "MDR-1", 
      "potent anticancer agent", 
      "complex formation", 
      "DNA damage", 
      "DNA repair", 
      "apoptosis", 
      "preclinical and clinical data", 
      "baseline", 
      "Phase I study", 
      "National Cancer Institute", 
      "QDs", 
      "patient", 
      "agent", 
      "pharmacokinetics", 
      "evidence", 
      "drug accumulation", 
      "dosing", 
      "peak level", 
      "exposure", 
      "clinical activity", 
      "safety", 
      "primary objective", 
      "tolerability", 
      "maximum tolerated dose", 
      "pharmacokinetic profile", 
      "secondary objective", 
      "Evaluate", 
      "tumor biopsy", 
      "Organization and Administration", 
      "marker", 
      "Caspase 3", 
      "organ function", 
      "study design", 
      "dose", 
      "Appointment and Schedule", 
      "additional patient", 
      "study drug"
    ], 
    "name": "A Phase I Trial of Weekly Indenoisoquinoline LMP400 in Adults With Relapsed Solid Tumors and Lymphomas", 
    "sameAs": [
      "https://app.dimensions.ai/details/clinical_trial/NCT01794104"
    ], 
    "sdDataset": "clinical_trials", 
    "sdDatePublished": "2019-03-07T15:24", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "file:///pack/app/us_ct_data_00014.json", 
    "sponsor": [
      {
        "id": "https://www.grid.ac/institutes/grid.48336.3a", 
        "type": "Organization"
      }, 
      {
        "id": "https://www.grid.ac/institutes/grid.410305.3", 
        "type": "Organization"
      }
    ], 
    "startDate": "2013-02-01T00:00:00Z", 
    "subjectOf": [
      {
        "id": "https://doi.org/10.1146/annurev.biochem.70.1.369", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003244224"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrm831", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1016798649", 
          "https://doi.org/10.1038/nrm831"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrc1977", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1028961158", 
          "https://doi.org/10.1038/nrc1977"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "type": "MedicalStudy", 
    "url": "https://clinicaltrials.gov/show/NCT01794104"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/clinicaltrial.NCT01794104'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/clinicaltrial.NCT01794104'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/clinicaltrial.NCT01794104'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/clinicaltrial.NCT01794104'


 

This table displays all metadata directly associated to this object as RDF triples.

107 TRIPLES      16 PREDICATES      94 URIs      84 LITERALS      1 BLANK NODES

Subject Predicate Object
1 sg:clinicaltrial.NCT01794104 schema:about anzsrc-for:3164
2 schema:description Background: - Indenoisoquinoline LMP400 is an experimental cancer treatment drug. It damages DNA in tumor cells. Tumor cells with damaged DNA may die, resulting in cell death. Researchers want to see if this drug is a safe and effective treatment for solid tumors and lymphomas that have not responded to earlier treatment. Objectives: - To see if Indenoisoquinoline LMP400 is a safe and effective treatment for advanced solid tumors or lymphomas. Eligibility: - Individuals at least 18 years of age who have solid tumors or lymphomas that have not responded to treatment. Design: - Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Tumor samples may also be collected. The size and location of the tumors will be determined with imaging studies. - Indenoisoquinoline LMP400 is given in a 28-day cycle. Participants will receive the drug by intravenous infusion on days 1, 8, and 15 of each cycle, followed by a break of 13 days without the drug. - Treatment will be monitored with frequent blood tests and imaging studies. Tumor samples will be optional. - Participants will continue their cycles of treatment as long as the cancer does not grow and there are no severe side effects. Detailed Description Background: - Indenoisoquinolines are non-camptothecin topoisomerase (Top1) inhibitors that form stable DNA-Top1 cleavage-complexes, have a preference for unique DNA cleavage sites, and are active against camptothecin-resistant cell lines. Unlike camptothecins, indenoisoquinolines are chemically stable and active in cells that over-express ATP-binding cassette (ABC) transporters ABCG2 and multidrug resistance (MDR-1). Top1 inhibitors are potent anticancer agents because stabilizing cleavage complex formation induces replication-and transcription-mediated DNA damage and delays DNA repair, leading to apoptosis. Preclinical and clinical data indicate that baseline tumor levels of Top1 correlate strongly with ability to respond to Top1 inhibitor therapy. - A first-in-human Phase I study conducted at the NCI of the indenoisoquinoline LMP400 (NSC 743400) on a QD x 5 q28 schedule in patients with refractory solid tumors and lymphomas (10-C-0056) established that this agent is well tolerated. LMP400 shows linear pharmacokinetics with evidence of drug accumulation following 5 days of dosing. We hypothesize that weekly dosing (days 1, 8, 15 q28-day cycle) will increase LMP400 peak levels and exposures, improving clinical activity and safety. Primary Objectives: - To establish the safety and tolerability of weekly (days 1, 8, 15 q28-day cycle) LMP400 in patients with refractory solid tumors and lymphomas. - To establish the maximum tolerated dose (MTD) of weekly LMP400 in patients with refractory solid tumors and lymphomas. - To evaluate the pharmacokinetic profile of weekly LMP400. Secondary Objectives: - Evaluate the level of Top1 in tumor biopsies pre- and post- administration of LMP400. - Evaluate the effect of LMP400 on markers of DNA damage and apoptosis, such as >=H2AX and caspase 3, in tumor biopsies pre- and post- LMP400 administration. Eligibility: -Patients with histologically confirmed metastatic solid tumors and lymphomas; adequate organ function. Study Design: - This is an open-label Phase I trial evaluating weekly administration of LMP400, on days 1, 8, and 15, in 28-day cycles. - Starting dose is based on the MTD determined from the QD x 5, q28 day schedule currently being evaluated. The study will follow a 3 plus 3 design. - Once the MTD is established, 10 additional patients will be enrolled at the MTD to further define the pharmacokinetics and evaluate effect of study drug on DNA damage and apoptosis.
3 schema:endDate 2017-10-01T00:00:00Z
4 schema:keywords ATP binding
5 ATP-binding cassette
6 Appointment and Schedule
7 Caspase 3
8 DNA damage
9 DNA repair
10 Evaluate
11 MDR-1
12 Multiple Drug Resistance
13 National Cancer Institute
14 Neoplasm
15 Organization and Administration
16 Phase I study
17 Phase I trial
18 QDs
19 Top1
20 additional patient
21 advanced solid tumor
22 age
23 agent
24 apoptosis
25 baseline
26 blood
27 camptothecin
28 cancer treatment
29 cassette
30 cell death
31 cleavage
32 cleavage site
33 clinical activity
34 complex formation
35 cycle
36 damage DNA
37 damaged DNA
38 dose
39 dosing
40 drug
41 drug accumulation
42 eligibility
43 evidence
44 exposure
45 imaging study
46 indenoisoquinolines
47 individual
48 inhibitor
49 intravenous infusion
50 location
51 lymphoma
52 marker
53 maximum tolerated dose
54 medical history
55 organ function
56 patient
57 peak level
58 pharmacokinetic profile
59 pharmacokinetics
60 physical exam
61 potent anticancer agent
62 preclinical and clinical data
63 preference
64 primary objective
65 resistant cell line
66 safe and effective treatment
67 safety
68 secondary objective
69 severe side effect
70 solid tumor
71 study design
72 study drug
73 tolerability
74 topoisomerase
75 tumor biopsy
76 tumor cell
77 tumor sample
78 urine sample
79 schema:name A Phase I Trial of Weekly Indenoisoquinoline LMP400 in Adults With Relapsed Solid Tumors and Lymphomas
80 schema:sameAs https://app.dimensions.ai/details/clinical_trial/NCT01794104
81 schema:sdDatePublished 2019-03-07T15:24
82 schema:sdLicense https://scigraph.springernature.com/explorer/license/
83 schema:sdPublisher Ne3d4e1707ac2486d8aedd1c300e68b9e
84 schema:sponsor https://www.grid.ac/institutes/grid.410305.3
85 https://www.grid.ac/institutes/grid.48336.3a
86 schema:startDate 2013-02-01T00:00:00Z
87 schema:subjectOf sg:pub.10.1038/nrc1977
88 sg:pub.10.1038/nrm831
89 https://doi.org/10.1146/annurev.biochem.70.1.369
90 schema:url https://clinicaltrials.gov/show/NCT01794104
91 sgo:license sg:explorer/license/
92 sgo:sdDataset clinical_trials
93 rdf:type schema:MedicalStudy
94 Ne3d4e1707ac2486d8aedd1c300e68b9e schema:name Springer Nature - SN SciGraph project
95 rdf:type schema:Organization
96 anzsrc-for:3164 schema:inDefinedTermSet anzsrc-for:
97 rdf:type schema:DefinedTerm
98 sg:pub.10.1038/nrc1977 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028961158
99 https://doi.org/10.1038/nrc1977
100 rdf:type schema:CreativeWork
101 sg:pub.10.1038/nrm831 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016798649
102 https://doi.org/10.1038/nrm831
103 rdf:type schema:CreativeWork
104 https://doi.org/10.1146/annurev.biochem.70.1.369 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003244224
105 rdf:type schema:CreativeWork
106 https://www.grid.ac/institutes/grid.410305.3 schema:Organization
107 https://www.grid.ac/institutes/grid.48336.3a schema:Organization
 




Preview window. Press ESC to close (or click here)


...