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Phase I Study of Trientine and Carboplatin in Patients With Advanced Malignancies


Phase 1
N/A
N/A
Open (Enrolling)
Both
Advanced Cancers

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Trial Information

Phase I Study of Trientine and Carboplatin in Patients With Advanced Malignancies


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:

- You will have a physical exam, including measurement of your weight and vital signs.

- You will be asked how well you are able to perform the normal activities of daily
living (performance status).

- Blood (about 2 teaspoons) will be drawn for routine tests.

- Blood (about 1 1/2 tablespoons) will be drawn to measure the levels of ceruloplasmin
(copper-carrying protein) copper, and iron in your blood.

- Women who are able to become pregnant must have a negative blood (about 1 teaspoon)
pregnancy test.

- If your doctor thinks it is needed, you may have an electrocardiogram (ECG) and/or an
echocardiogram (ECHO) to check your heart function. An ECG is a test that measures the
electrical activity of the heart

Every week until the doctor decides your are taking the correct dose of trientine:

- Blood (about 1 teaspoon) will be drawn for routine tests.

- Blood (about 2 teaspoons) will be drawn to measure the levels of ceruloplasmin in your
blood.

Every week during Cycle 1, blood (about 1 teaspoon) will be drawn for routine tests.

Once each cycle:

- Your medical history will be recorded.

- You will have a physical exam, including measurement of your weight and vital signs.

- Your performance status will be recorded.

- Blood (about 2 teaspoons) will be drawn for routine tests.

- If your study doctor thinks it is needed, blood (about 1 tablespoon) will be drawn to
measure levels of copper and iron in your blood.

- You will be asked about any side effects you may be having.

At the end of every 2 cycles (Cycles 2, 4, 6, and so on):

- You will have a CT, MRI, PET scan, and/or x-ray to check the status of the disease.

- If the study doctor thinks it is needed, blood (about 1 teaspoon) will be drawn to
measure tumor markers.

PK Groups:

If you are in PK Group A, blood (about 1 teaspoon each time) will be drawn:

- On Day 1 of Cycle 1, blood will be drawn 7 times over the 6 hours after you receive
carboplatin.

- On Day 2 of Cycle 1, blood will be drawn 1 time.

- On Day 1 of Cycle 2, blood will be drawn 7 times over the 6 hours after you receive
carboplatin.

- On Day 2 of Cycle 2, blood will be drawn 1 time.

If you are in PK Group B, blood (about 1 teaspoon each time) will be drawn:

- On Day 21 of Cycle 1, blood will be drawn 7 times over the 6 hours after your dose of
trientine.

- On Day 22 of Cycle 1, will be drawn 1 time.

- On Day 1 of Cycle 2, will be drawn 7 times over the 6 hours after you receive
carboplatin.

- On Day 2 of Cycle 2, blood will be drawn 1 time.

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:

- Your medical history will be recorded.

- You will have a physical exam, including measurement of your weight and vital signs.

- Your performance status will be recorded.

- Blood (about 2 teaspoons) will be drawn for routine tests.

- You will be asked about any side effects you may be experiencing.

- If the study doctor thinks it is needed, blood (about 1 teaspoon) will be drawn to
measure tumor markers.

- If the study doctor thinks it is needed, you will have a chest x-ray, CT, MRI, and/or
PET scan to check the status of the disease.

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.


Inclusion Criteria:



1. Patient must have an advanced malignancy that has either failed one or more prior
therapies, or for whom there is no established standard of care therapy that prolongs
survival by at least 3 months.

2. Only in 1 of 3 expansion cohorts, we will plan to enroll 14 subjects with
platinum-resistant malignancy. Patient with platinum-resistant malignancy is defined
to have had a treatment-free interval of less than 6 months following a
platinum-based regimen.

3. Patient of any age and any gender. However, those who are 12 years old or younger
will be eligible after consultation with their pediatric physicians regarding dose
initiation and modification of trientine.

4. Patient has an ECOG performance status of 0-2.

5. Patient is willing to comply with study procedures and follow-up examinations.

6. Patient or primary care taker must be informed of the investigational nature of this
study and must sign and give written IRB-approved informed consent in accordance with
institutional guidelines.

7. If patient is of childbearing potential, she or he must agree to practice an
effective method of birth control prior to study entry, for the duration of study
participation, and for 30 days after the last study dose.

8. Patient has adequate organ functions: serum bilirubin upper limit of normal (ULN), or ALT metastasis; serum creatinine least 60 mL/min.

9. Patient has adequate bone marrow reserve: ANC >/= 1,500 /ul, Platelet count >/=
100,000 /ul , and Hemoglobin >/= 9.0 g/dL.

Exclusion Criteria:

1. Patient receiving any concurrent chemotherapy.

2. Underlying medical condition that might be aggravated by treatment or that cannot be
controlled, such as active, uncontrolled, serious infection and cardiac dysfunction.

3. Medical and/or psychiatric problems of sufficient severity to limit full compliance
with the study or expose patients to undue risk.

4. Known anaphylactic or severe hypersensitivity to study drugs or their analogs.

5. Patient has failed to recover from any prior surgery within 4 weeks of study entry.

6. Patient is pregnant or lactating.

7. Patient has had any treatment specific for tumor control within 3 weeks of dosing
with investigational drugs and cytotoxic agents, or within 2 weeks of cytotoxic agent
given weekly, or within 6 weeks of nitrosoureas or mitomycin C, or within 5
half-lives of biological targeted agents with half-lives and pharmacodynamic effects
lasting less than 5 days (that includes, but is not limited to, erlotinib, sorafenib,
sunitinib, bortezomib, and other similar agents), or failure to recover from the
toxic effect of any of these therapies prior to study entry.

8. Patient has any signs of intestinal obstruction interfering with nutrition.

9. Patient has a known history of CNS metastasis unless the patient has had treatment
with surgery or radiation therapy, and is neurologically stable.

10. Patient is not able to swallow oral medication.

11. Patient has clinical evidence of copper deficiency (i.e. ceruloplasmin level was less
than 15 mg/dL or free serum copper level less than 2.2 ug/dL).

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose (MTD) of Carboplatin with Trientine

Outcome Time Frame:

Each 28 day cycle

Safety Issue:

No

Principal Investigator

Siqing Fu, MD, PHD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

2010-0258

NCT ID:

NCT01178112

Start Date:

July 2010

Completion Date:

Related Keywords:

  • Advanced Cancers
  • Metastasis
  • Carboplatin
  • Trientine
  • Chemotherapy
  • Neoplasms

Name

Location

UT MD Anderson Cancer CenterHouston, Texas  77030