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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2012-01787 | Registry Identifier | NCI CTRP |
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The goal of this clinical research study is to find the highest tolerable dose of the combination of trientine and carboplatin that can be given to patients with advanced cancer. The safety of this drug combination will also be studied.
The Study Drugs:
Trientine is designed to remove excess copper in the body, which may cause cancer cells to stop growing.
Carboplatin is designed to block the growth of cancer cells by stopping cell division, which may cause the cells to die.
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a dose level of carboplatin based on when you joined this study. Up to 3 dose levels of the carboplatin will be tested.
Three (3) to 6 participants will be enrolled at each dose level of carboplatin. The first group of participants will receive the lowest dose level of carboplatin . Each new group will receive a higher dose of the carboplatin than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of the study drug combination is found.
The dose level of trientine will be based on your blood levels of copper. These levels may vary from person to person.
Expansion Groups:
Once the highest tolerable dose of the study drug combination is found, there will be two expansion groups, one group of 28 extra participants (Group A) and one group of 14 extra participants (Group B). Group A will receive the study combination at the highest tolerable dose. Group B will receive extra doses of trientine before starting Day 1 of Cycle 1.
Pharmacokinetic (PK) Groups:
In additional the the Expansion Groups, once the highest tolerable dose of the study drug combination is found, there will also be 2 PK groups. PK testing measures the amount of study drug in the body at different time points. There will be 6 participants in each group. These groups will also receive the study combination at the highest tolerable dose. There will be extra blood draws for both groups and the drug administration schedule will be different from the groups described above.
For all participants, your dose of the study drugs may be lowered if you have any intolerable side effects. You will not receive a higher dose than the dose level that you are first assigned.
Study Drug Administration:
Dose Escalation and Expansion Groups:
On Day 1 of each 28-day cycle, you will receive carboplatin by vein over 2 hours.
Starting on Day 1 of Cycle 1, you will begin taking trientine by mouth several times each day. If you are in Expansion Group B, you will receive extra doses of trientine within the 14 days before Day 1 of Cycle 1. Your study doctor will tell you when to take trientine and whether it should be taken with or without food. You will also be told how many pills to take.
PK Groups:
Both groups will take the study drugs as described above.
However, if you are in PK Group A, instead of on Day 1 of Cycle 1, you will start taking trientine daily beginning on Day 2 of Cycle 1.
If you are in PK Group B, on Day 21 of Cycle 1 and Day 1 of Cycle 2 you will not eat for 2 hours before and 2 hours after you take trientine.
Study Visits:
Within 7 days before the first dose of study drug:
Every week until the doctor decides your are taking the correct dose of trientine:
Every week during Cycle 1, blood (about 1 teaspoon) will be drawn for routine tests.
Once each cycle:
At the end of every 2 cycles (Cycles 2, 4, 6, and so on):
PK Groups:
If you are in PK Group A, blood (about 1 teaspoon each time) will be drawn:
If you are in PK Group B, blood (about 1 teaspoon each time) will be drawn:
Length of Study:
You may continue taking the study drugs for as long as the doctor thinks it is in your best interest. You will be taken off study early if the disease gets worse or you experience intolerable side effects.
Your participation on the study will be over once you have completed the end-of-study visit.
End-of-Study Visit:
Within 30 days after your last dose of study drugs, you will have an end-of-study visit. At this visit, the following tests and procedures performed:
This is an investigational study. Trientine is FDA approved and commercially available for the treatment of Wilson's disease. Trientine is not FDA approved for the treatment of advanced cancer. Carboplatin is FDA approved and commercially available for the treatment of ovarian cancer. The combination of trientine and carboplatin to treat advanced cancer is investigational.
Up to 72 patients will take part in this study. All will be enrolled at MD Anderson.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Trientine + Carboplatin MTD Group | Experimental | Trientine starting dose 750 mg by mouth four times a day, two times with meals and two times without meals for 28 days. Carboplatin maximum tolerated dose found in MTD Dose Escalation Group. |
|
| MTD Expansion Group | Experimental | Trientine maximum tolerated dose found in MTD Dose Escalation Group; Carboplatin PK Group A, instead of starting on Day 1 of Cycle 1, starts taking trientine daily beginning on Day 2 of Cycle 1. Trientine PK Group B, 1500 mg of trientine is given once without food on Day 21 of Cycle 1 and once without food after the completion of carboplatin on Day 1 of Cycle 2. Carboplatin maximum tolerated dose found in MTD Dose Escalation Group |
|
| Carboplatin PK Expansion Group | Experimental | Trientine maximum tolerated dose found in MTD Dose Escalation Group; Carboplatin PK Group A, instead of starting on Day 1 of Cycle 1, starts taking trientine daily beginning on Day 2 of Cycle 1. Trientine PK Group B, 1500 mg of trientine is given once without food on Day 21 of Cycle 1 and once without food after the completion of carboplatin on Day 1 of Cycle 2. Carboplatin maximum tolerated dose found in MTD Dose Escalation Group. PK testing blood samples of 4 mL at following time points: 0, 30, 60 minutes, 2, 3, 4, 6, and 24 hours. |
|
| Trientine PK Expansion Group | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Trientine | Drug | Starting dose 750 mg by mouth four times a day, two times with meals and two times without meals for 28 days. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Tolerated Dose (MTD) of Carboplatin with Trientine | MTD defined by dose limiting toxicities (DLTs) that occur in the first cycle (4 weeks). DLT defined as treatment-related grade 3 or greater nonhematological toxicity other than nausea, vomiting, or fatigue. | 4 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Treatment Response of Maximum Tolerated Dose (MTD) of Carboplatin with Trientine | Categorization of response based on immune-related response criteria and Response Evaluation Criteria in Solid Tumors (RECIST). | After 2, 28 day cycles |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Siqing Fu, MD, PHD | UT MD Anderson Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Texas MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22491798 | Derived | Fu S, Naing A, Fu C, Kuo MT, Kurzrock R. Overcoming platinum resistance through the use of a copper-lowering agent. Mol Cancer Ther. 2012 Jun;11(6):1221-5. doi: 10.1158/1535-7163.MCT-11-0864. Epub 2012 Apr 5. |
| Label | URL |
|---|---|
| University of Texas MD Anderson Cancer Center Website | View source |
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| ID | Term |
|---|---|
| D009362 | Neoplasm Metastasis |
| ID | Term |
|---|---|
| D009385 | Neoplastic Processes |
| D009369 | Neoplasms |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D014266 | Trientine |
| D016190 | Carboplatin |
| ID | Term |
|---|---|
| D005029 | Ethylenediamines |
| D003959 | Diamines |
| D011073 | Polyamines |
| D000588 | Amines |
| D009930 |
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Trientine maximum tolerated dose found in MTD Dose Escalation Group; Carboplatin PK Group A, instead of starting on Day 1 of Cycle 1, starts taking trientine daily beginning on Day 2 of Cycle 1. Trientine PK Group B, 1500 mg of trientine is given once without food on Day 21 of Cycle 1 and once without food after the completion of carboplatin on Day 1 of Cycle 2. Carboplatin maximum tolerated dose found in MTD Dose Escalation Group. PK testing blood samples of 4 mL at following time points: 0, 30, 60 minutes, 2, 3, 4, 6, and 24 hours.
|
| Carboplatin | Drug | Starting dose area under curve (AUC) 4 by vein over two hours on day 1, and once every 28 days. |
|
|
| Trientine MTD | Drug | Maximum tolerated dose found in MTD Dose Escalation Group; Carboplatin PK Group A, instead of starting on Day 1 of Cycle 1, starts taking trientine daily beginning on Day 2 of Cycle 1. Trientine PK Group B, 1500 mg of trientine is given once without food on Day 21 of Cycle 1 and once without food after the completion of carboplatin on Day 1 of Cycle 2. |
|
| Carboplatin MTD | Drug | Maximum tolerated dose found in MTD Dose Escalation Group |
|
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| PK Testing | Other | Blood samples of 4 mL at following time points: 0, 30, 60 minutes, 2, 3, 4, 6, and 24 hours. |
|
| Organic Chemicals |
| D056831 | Coordination Complexes |