Pharmacokinetic Study of Liposomal Vincristine in Patients With Malignant Melanoma & Hepatic Dysfunction
Study Details
Study Description
Brief Summary
The purpose of this study is to see how vincristine, when placed in an oil droplet called a liposome (VSLI), is absorbed, distributed (moved around) and excreted from the the body (pharmacokinetics). This study will also assess the safety of VSLI and to see if VSLI will slow the growth or shrink tumors in patients with metastatic melanoma that has resulted in liver impairment, and who have relapsed after previous therapies.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
OBJECTIVES:
Primary: To assess the pharmacokinetics of VSLI administered intravenously to patients with malignant melanoma and hepatic dysfunction secondary to metastases.
Secondary: To assess the safety and antitumor activity of VSLI in this population.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: VSLI Single armed study; all subjects received VSLI |
Drug: Vincristine Sulfate Liposomes Injection
Marqibo (VSLI) 1.0 mg/m2 delivered by intravenous infusion over 1 hour every 2 weeks.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- T 1/2 [cycle 1 day 1]
The PK profiles of total plasma VCR following a single intravenous infusion at a target dose of 1.0 mg/m2 for approximately 1 hour every 2 weeks (one cycle) to three male and four female subjects with malignant melanoma and hepatic dysfunction secondary to metastases were measured.
- Clearance [Day 1 of Cycle 1]
The pharmacokinetic profile of VCR on Day 1 of Cycle 1 Cl is mL/h/m2
- Volume of Distribution [cycle 1 day 1]
The PK profiles of total plasma VCR following a single intravenous infusion at a target dose of 1.0 mg/m2 for approximately 1 hour
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients must have histologically confirmed, surgically nonresectable Stage III or IV metastatic cutaneous, mucosal, or choroidal melanoma, and not be eligible for a treatment protocol of a higher priority.
-
Patients must have secondary tumor involvement of the liver confirmed by CT scan and a bilirubin level of 1.6-3.0 mg/dL (National Cancer Institute, Common Terminology Criteria for Adverse Events Grade 2) (MD Anderson Cancer Center normal range is 0-1.0 mg/dL).
-
Patients must have bidimensionally measurable disease.
-
Patients with nonchoroidal melanoma must have received prior chemotherapy for metastatic disease with cytotoxic or biological drugs. Patients with choroidal melanoma may or may not have received prior chemotherapy for metastatic disease with cytotoxic or biological drugs.
-
Patients must have a Performance Status of 0, 1, 2, or 3 (Zubrod Scale).
-
Patients must have recovered from the adverse effects of prior chemotherapy (including cytotoxic agents and biological response modifiers), and/or irradiation therapy.
-
Patients must have an absolute neutrophil count ≥1.0 x 109/L and a platelet count of ≥100 x 109/L.
-
Patients must have adequate renal function demonstrated by a creatinine level of ≤2.0 mg/dL.
-
Patients must have a life expectancy of >8 weeks.
-
Patients must provide a signed informed consent document indicating that they are aware of the investigational nature of this study in keeping with the policies of the hospital.
Exclusion Criteria:
-
Patients treated with radiotherapy, chemotherapy, immunotherapy, vaccine treatment and/or alternative anticancer treatments (including investigational drugs) within 3 weeks prior to study enrollment.
-
Patients treated with hepatic chemo-embolization within 4 weeks prior to study enrollment.
-
Patients with severe hepatic impairment demonstrated by plasma ammonia levels >105 mMol/L or serum albumin <2.0 g/dL or serum bilirubin >3.0 mg/dL.
-
Patients with serious intercurrent illness.
-
Patients who have had major surgery within 4 weeks of enrollment.
-
Patients with advanced symptomatic central nervous system (CNS) involvement by melanoma and those on phenytoin or requiring steroids for brain metastases, spinal cord compression, or meningeal "carcinomatosis".Patients with asymptomatic and stable metastatic CNS disease can be enrolled.
-
Patients receiving treatment with phenytoin and/or corticosteroids within 1 week of enrollment. Patients must remain off of these medications for the duration of the treatment phase of the study.
-
Patients with a history of neurological disorders unrelated to chemotherapy (including familial neurological diseases and acquired demyelinating disorders).
-
Patients with Grade 3 or greater sensory, motor or autonomic neuropathy at screening from any cause.
-
Patients receiving treatment with drugs known to inhibit or induce hepatic drug metabolism by cytochrome P450-3A4 isoenzymes and/or P-glycoprotein within 1 week of study enrollment. Patients must remain off of these drugs until the collection of the Cycle 4 pretreatment PK sample.
-
Patients with past or current history of liver parenchymal or hepatobiliary disease unrelated to cancer (including but not limited to conditions such as liver cirrhosis, acute/chronic hepatitis, ascending cholangitis, etc).
-
Patients who are pregnant or lactating. Females of childbearing potential must have a negative urine or blood pregnancy test at screening. Both men and women must be practicing an adequate method of birth control for the duration of the study. Acceptable methods of birth control include use of an intrauterine device (IUD), oral contraceptive pills, implanted, transdermal, or injected contraceptives, barrier methods with spermicide, and abstinence.
-
Patients who are unable to return for follow up re-evaluation and assessment of response to VSLI.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Texas M.D. Anderson Cancer Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- Acrotech Biopharma LLC
Investigators
- Principal Investigator: Agop Bedikian, MD, MD Anderson Cancer Center, Dept of Melanoma
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- VSLI-12-HEPHARM
Study Results
Participant Flow
| Recruitment Details | This was a single-center, open-label, single-arm, Phase 1 study to assess the PK of VSLI in subjects with malignant melanoma and hepatic dysfunction secondary to liver metastases. |
|---|---|
| Pre-assignment Detail | Eligible subjects were to have liver metastases confirmed by computed tomography (CT) scan at screening. Categorization of hepatic dysfunction at screening included Child-Pugh System. |
| Arm/Group Title | Overall Study |
|---|---|
| Arm/Group Description | This was a non-randomized, open-label, single arm, single-center Phase 1 study. All subjects received the same treatment. All subjects received Marqibo (VSLI) 1.0 mg/m2 delivered by intravenous infusion over 1 hour every 2 weeks. |
| Period Title: Overall Study | |
| STARTED | 7 |
| COMPLETED | 7 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | Overall Study |
|---|---|
| Arm/Group Description | This was a non-randomized, open-label, single arm, single-center Phase 1 study. All subjects received the same treatment. All subjects received Marqibo (VSLI) 1.0 mg/m2 delivered by intravenous infusion over 1 hour every 2 weeks. |
| Overall Participants | 7 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
4
57.1%
|
| >=65 years |
3
42.9%
|
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
60.7
(8.10)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
4
57.1%
|
| Male |
3
42.9%
|
| Region of Enrollment (participants) [Number] | |
| United States |
7
100%
|
Outcome Measures
| Title | T 1/2 |
|---|---|
| Description | The PK profiles of total plasma VCR following a single intravenous infusion at a target dose of 1.0 mg/m2 for approximately 1 hour every 2 weeks (one cycle) to three male and four female subjects with malignant melanoma and hepatic dysfunction secondary to metastases were measured. |
| Time Frame | cycle 1 day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| all patients enrolled |
| Arm/Group Title | Overall Study |
|---|---|
| Arm/Group Description | This was a non-randomized, open-label, single arm, single-center Phase 1 study. All subjects received the same treatment. All subjects received Marqibo (VSLI) 1.0 mg/m2 delivered by intravenous infusion over 1 hour every 2 weeks. |
| Measure Participants | 7 |
| Mean (Standard Deviation) [hr] |
9.94
(1.22)
|
| Title | Clearance |
|---|---|
| Description | The pharmacokinetic profile of VCR on Day 1 of Cycle 1 Cl is mL/h/m2 |
| Time Frame | Day 1 of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All subjects enrolled |
| Arm/Group Title | Overall Study |
|---|---|
| Arm/Group Description | This was a non-randomized, open-label, single arm, single-center Phase 1 study. All subjects received the same treatment. All subjects received Marqibo (VSLI) 1.0 mg/m2 delivered by intravenous infusion over 1 hour every 2 weeks. |
| Measure Participants | 7 |
| Mean (Standard Deviation) [ml/h/m2] |
193
(80.3)
|
| Title | Volume of Distribution |
|---|---|
| Description | The PK profiles of total plasma VCR following a single intravenous infusion at a target dose of 1.0 mg/m2 for approximately 1 hour |
| Time Frame | cycle 1 day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| all patients enrolled |
| Arm/Group Title | Overall Study |
|---|---|
| Arm/Group Description | This was a non-randomized, open-label, single arm, single-center Phase 1 study. All subjects received the same treatment. All subjects received Marqibo (VSLI) 1.0 mg/m2 delivered by intravenous infusion over 1 hour every 2 weeks. |
| Measure Participants | 7 |
| Mean (Standard Deviation) [mL/m2] |
2722
(1066)
|
Adverse Events
| Time Frame | The AE reporting period for this study was from the time of the first dose of VSLI until 30 days after the last dose of VSLI. | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Overall Study | |
| Arm/Group Description | This was a non-randomized, open-label, single arm, single-center Phase 1 study. All subjects received the same treatment. All subjects received Marqibo (VSLI) 1.0 mg/m2 delivered by intravenous infusion over 1 hour every 2 weeks. | |
All Cause Mortality |
||
| Overall Study | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Overall Study | ||
| Affected / at Risk (%) | # Events | |
| Total | 7/7 (100%) | |
| Blood and lymphatic system disorders | ||
| Disseminated intravascular coagulation | 1/7 (14.3%) | 1 |
| Cardiac disorders | ||
| Cardiac arrest | 1/7 (14.3%) | 1 |
| Gastrointestinal disorders | ||
| Constipation | 1/7 (14.3%) | 1 |
| General disorders | ||
| Multi-organ failure | 1/7 (14.3%) | 1 |
| Ascites | 1/7 (14.3%) | 1 |
| Abdominal pain upper | 1/7 (14.3%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||
| Dyspnoea | 1/7 (14.3%) | 1 |
| Pleural effusion | 1/7 (14.3%) | 1 |
| Skin and subcutaneous tissue disorders | ||
| Malignant melanoma | 3/7 (42.9%) | 3 |
| Disease progression | 1/7 (14.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| Overall Study | ||
| Affected / at Risk (%) | # Events | |
| Total | 7/7 (100%) | |
| Blood and lymphatic system disorders | ||
| anaemia | 1/7 (14.3%) | 1 |
| disseminated intravascular coagulation | 1/7 (14.3%) | 1 |
| Cardiac disorders | ||
| cardiac arrest | 1/7 (14.3%) | 1 |
| Gastrointestinal disorders | ||
| Constipation | 3/7 (42.9%) | 3 |
| Vomitting | 1/7 (14.3%) | 1 |
| General disorders | ||
| Fatigue | 4/7 (57.1%) | 4 |
| Decreased appetite | 4/7 (57.1%) | 4 |
| Ascites | 3/7 (42.9%) | 3 |
| Nausea | 3/7 (42.9%) | 3 |
| Oedema, peripheral | 2/7 (28.6%) | 2 |
| Pyrexia | 2/7 (28.6%) | 2 |
| Insomnia | 2/7 (28.6%) | 2 |
| Abdominal distention | 1/7 (14.3%) | 1 |
| Abdominal pain, upper | 1/7 (14.3%) | 1 |
| Multi-organ failure | 1/7 (14.3%) | 1 |
| Oedema | 1/7 (14.3%) | 1 |
| Hypomagnesaemia | 1/7 (14.3%) | 1 |
| Hyponatraemia | 1/7 (14.3%) | 1 |
| tumor pain | 1/7 (14.3%) | 1 |
| sleep disorder | 1/7 (14.3%) | 1 |
| drug hypersensitivity | 1/7 (14.3%) | 1 |
| seasonal allergy | 1/7 (14.3%) | 1 |
| weight increased | 1/7 (14.3%) | 1 |
| night sweats | 1/7 (14.3%) | 1 |
| menopause | 1/7 (14.3%) | 1 |
| hypotension | 1/7 (14.3%) | 1 |
| Hepatobiliary disorders | ||
| blood bilirubin increased | 1/7 (14.3%) | 1 |
| hyperbilirubinaenemia | 1/7 (14.3%) | 1 |
| Infections and infestations | ||
| central line infection | 1/7 (14.3%) | 1 |
| Musculoskeletal and connective tissue disorders | ||
| arthralgia | 1/7 (14.3%) | 1 |
| rheumatoid arthritis | 1/7 (14.3%) | 1 |
| Nervous system disorders | ||
| Anxiety | 2/7 (28.6%) | 2 |
| Gait disturbance | 1/7 (14.3%) | 1 |
| confusional state | 1/7 (14.3%) | 1 |
| depression | 1/7 (14.3%) | 1 |
| neuropathy, peripheral | 1/7 (14.3%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||
| pleural effusion | 1/7 (14.3%) | 1 |
| Skin and subcutaneous tissue disorders | ||
| Malignant melanoma | 4/7 (57.1%) | 4 |
| rash | 1/7 (14.3%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Chief Medical Officer |
|---|---|
| Organization | Talon Therapeutics |
| Phone | 650-588-6404 |
| info@talontx.com |
- VSLI-12-HEPHARM