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This phase I study aims to assess the safety and tolerability of a new drug - PG-11047 - and to establish what happens to the drug once inside the body. An escalating dose of PG-11047 will be investigated in this study and the maximum tolerated dose of the drug will be established.
This is an open-label phase I, dose-escalation safety study in subjects with refractory solid tumors. The primary objectives of the study are to assess the safety, tolerability, and pharmacokinetics of PG-11047. PG-11047 will be administered as a 60-minute intravenous infusion on days 1, 8 and 15 of each 28 day cycle. The planned minimum treatment schedule is 2 cycles (8 weeks) of PG-11047 treatment. Subjects who tolerate treatment may be eligible to receive additional cycles as per investigator's medical judgment. Evaluation of anti-tumor response will be performed every 2 cycles.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PG-11047 | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PG-11047 | Drug | PG-11047 will be administered as a 60-minute intravenous infusion on days 1, 8 and 15 of each 28 day cycle. A treatment cycle will be defined as 4 weeks of therapy. The planned minimum treatment schedule is 2 cycles of PG-11047 treatment (8 weeks). |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Tolerated Dose (MTD) | The MTD was defined as the dose below one-third of at least 6 subjects (e.g., 2/6, 3/9, 4/12) experienced a Dose-limiting toxicity (DLT). Dose-limiting toxicities (DLTs) used to determine the MTD had to occur during cycle 1 of treatment and had to be considered related to PG-11047. | The MTD had to occur during cycle 1 of treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Preliminary Efficacy | As per RECIST Criteria (V 1.0) by radiologic evaluations: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR) >= 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD), >= 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Mark Ratain, M.D. | University of Chicago | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Chicago, Cancer Research Centre | Chicago | Illinois | 60637 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32447421 | Derived | Murray Stewart T, Desai AA, Fitzgerald ML, Marton LJ, Casero RA Jr. A phase I dose-escalation study of the polyamine analog PG-11047 in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2020 Jun;85(6):1089-1096. doi: 10.1007/s00280-020-04082-4. Epub 2020 May 23. |
| Label | URL |
|---|---|
| Progen Pharmaceuticals website | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | PG-11047 | Multiple-ascending dose of PG-11047 monotherapy. 60 minute infusion on days 1, 8 and 15 of a 28 day cycle. Dosage was escalated from 50 mg to 750 mg |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | PG-11047 | Multiple-ascending dose of PG-11047 monotherapy. 60 minute infusion on days 1, 8 and 15 of a 28 day cycle. Dosage was escalated from 50 mg to 750 mg |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Secondary | Preliminary Efficacy | As per RECIST Criteria (V 1.0) by radiologic evaluations: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR) >= 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD), >= 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. | Patients with non-missing overall response | Posted | Number | percentage (of participants) | For the purposes of this study, patients were reevaluated radiologically every 8 weeks. In addition to a baseline scan, confirmatory scans were obtained 6-8 weeks following initial documentation of an objective response, when appropriate. |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | PG-11047 | Multiple-ascending dose of PG-11047 monotherapy. 60 minute infusion on days 1, 8 and 15 of a 28 day cycle. Dosage was escalated from 50 mg to 750 mg |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment | 1 unrelated to PG-11047; 2 unlikely related to PG-11047 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Constipation | Gastrointestinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Michael Fitzgerald | Progen Industries | 919-803-9988 | michaelf@progen-pharma.com |
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| ID | Term |
|---|---|
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C415967 | (N(1),N(12))bis(ethyl)-6,7-dehydrospermine |
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| For the purposes of this study, patients were reevaluated radiologically every 8 weeks. In addition to a baseline scan, confirmatory scans were obtained 6-8 weeks following initial documentation of an objective response, when appropriate. |
| Participants |
|
| Age Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
Multiple-ascending dose of PG-11047 monotherapy. 60 minute infusion on days 1, 8 and 15 of a 28 day cycle. Dosage was escalated from 50 mg to 750 mg |
|
|
| Primary | Maximum Tolerated Dose (MTD) | The MTD was defined as the dose below one-third of at least 6 subjects (e.g., 2/6, 3/9, 4/12) experienced a Dose-limiting toxicity (DLT). Dose-limiting toxicities (DLTs) used to determine the MTD had to occur during cycle 1 of treatment and had to be considered related to PG-11047. | Posted | Number | mg | The MTD had to occur during cycle 1 of treatment |
|
|
|
| 25 |
| 46 |
| 46 |
| 46 |
|
| Alteration in mental status | Nervous system disorders | MedDRA (Unspecified) | Non-systematic Assessment | Unlikely related to PG-11047 |
|
| Anemia | Blood and lymphatic system disorders | MedDRA (Unspecified) | Non-systematic Assessment | 2 possibly related to PG-11047 |
|
| Angioedema | Skin and subcutaneous tissue disorders | MedDRA (Unspecified) | Non-systematic Assessment | Probably related to PG-11047 |
|
| Aspiration pneumonitis | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment | Unlikely related to PG-11047 |
|
| Bowel obstruction | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment | 1 unrelated to PG-11047; 4 unlikely related to PG-11047 |
|
| Bradycardia | Cardiac disorders | MedDRA (Unspecified) | Non-systematic Assessment | Possibly related to PG-11047 |
|
| Brain metastases | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (Unspecified) | Non-systematic Assessment | Unrelated to PG-011047 |
|
| Chest pain | Musculoskeletal and connective tissue disorders | MedDRA (Unspecified) | Non-systematic Assessment | Unlikely related to PG-11047 |
|
| Confusion | Nervous system disorders | MedDRA (Unspecified) | Non-systematic Assessment | Unrelated to PG-11047 |
|
| Constipation | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment | Unrelated to PG-11047 |
|
| Diarrhea | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment | Probably related to PG-11047 |
|
| Duodenal stricture | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment | Unlikely related to PG-11047 |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Non-systematic Assessment | 1 unrelated to PG-11047; 4 unlikely related to PG-11047; 2 possibly related to PG-11047 |
|
| Elevated amylase | Investigations | MedDRA (Unspecified) | Non-systematic Assessment | Unrelated to PG-11047 |
|
| Elevated bilirubin | Investigations | MedDRA (Unspecified) | Non-systematic Assessment | 1 unrelated to PG-11047; 1 unlikely related to PG-11047 |
|
| Elevated lipase | Investigations | MedDRA (Unspecified) | Non-systematic Assessment | Unrelated to PG-11047 |
|
| Fatigue | General disorders | MedDRA (Unspecified) | Non-systematic Assessment | Unlikely related to PG-11047 |
|
| GI bleed | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment | Unlikely related to PG-11047 |
|
| Gram negative bacteremia | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment | Unlikely related to PG-11047 |
|
| Infection | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment | Unlikely related to PG-11047 |
|
| Nausea | General disorders | MedDRA (Unspecified) | Non-systematic Assessment | 2 unlikely related to PG-11047 |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA (Unspecified) | Non-systematic Assessment | Unrelated to PG-11047 |
|
| Progressive disease | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (Unspecified) | Non-systematic Assessment | 2 unrelated to PG-11047, 1 unlikely related to PG-11047 |
|
| Pulmonary embolism | Cardiac disorders | MedDRA (Unspecified) | Non-systematic Assessment | Unlikely related to PG-11047 |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (Unspecified) | Non-systematic Assessment | Unrelated to PG-11047 |
|
| Right arm pain | Musculoskeletal and connective tissue disorders | MedDRA (Unspecified) | Non-systematic Assessment | Unrelated to PG-11047 |
|
| Vomitting | General disorders | MedDRA (Unspecified) | Non-systematic Assessment | 1 unrelated to PG-11047; 2 unlikely related to PG-11047 |
|
| Dizziness | General disorders | Systematic Assessment |
|
| Fatigue | General disorders | Systematic Assessment |
|
| Hypotension | Cardiac disorders | Systematic Assessment |
|
| Mucosal Inflammation | Gastrointestinal disorders | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Paraesthesia Oral | Nervous system disorders | Systematic Assessment |
|
| Parasethesia | Nervous system disorders | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | Systematic Assessment |
|
| anemia | Blood and lymphatic system disorders | Systematic Assessment |
|
| anorexia | Metabolism and nutrition disorders | Systematic Assessment |
|
| dysponea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
Any formal presentation or publication of data collected from this trial will be considered as a joint publication by the investigator(s) and the appropriate personnel of Progen. Authorship will be determined by mutual agreement.