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A Phase I, Open-label, Dose Escalation, Non-randomized Study to Assess the Pharmacokinetics, Dose Limiting Toxicity, and Maximum Tolerated Dose of OPB-31121 in Subjects With Advanced Solid Tumors


Phase 1
18 Years
N/A
Not Enrolling
Both
Advanced Cancer, Solid Tumor

Thank you

Trial Information

A Phase I, Open-label, Dose Escalation, Non-randomized Study to Assess the Pharmacokinetics, Dose Limiting Toxicity, and Maximum Tolerated Dose of OPB-31121 in Subjects With Advanced Solid Tumors


The Study Drug:

OPB-31121 is designed to block certain proteins in cancer cells that cause the cancer cells
to reproduce and form more cancer cells.

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a dose
level of OPB-31121 based on when you joined this study. The first group of participants
will receive the lowest dose level. Each new group will receive a higher dose than the
group before it, if no intolerable side effects were seen. This will continue until the
highest tolerable dose of OPB-31121 is found.

Study Drug Administration:

On Days 1-21 of each 28-day cycle, you will take the study drug by mouth 2 times a day. You
should take the study drug with at least 1 full glass of room temperature, still
(non-carbonated) water, within 30 minutes after eating a snack or meal. You should either
remain sitting upright or standing for at least 30 minutes after you take the study drug.
You will be given directions by the study doctor, the study nurse, and/or the study
pharmacist on how to take the study drug at home.

Study Visits:

On Day 1 of Cycle 1, the following tests and procedures will be performed:

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

- You will have 5 ECGs: 1 before the morning dose of study drug and at 1, 2, 4, and 8
hours after the morning dose.

- Blood (about 3 tablespoons) will be drawn for routine tests.

- Your performance status will be recorded.

- You will be asked about any drugs you may be taking and if you have experienced any
side effects.

- Blood (about 2 teaspoons each time) will be drawn before the morning dose and then 6
more times over the next 12 hours after the dose for pharmacokinetic (PK) testing. PK
testing measures the amount of study drug in the body at different time points.

- Blood (about 2 teaspoons) for pharmacodynamic (PD) testing will be drawn before the
morning dose. PD testing is used to look at how the level of study drug in your body
may affect the disease.

- Blood (about 1 teaspoon) will be drawn for pharmacogenomic (PGx) testing. PGx testing
looks at how differences in people's genes may affect if and how well the study drug
may affect the disease.

- Women who are able to become pregnant will have a urine pregnancy test.

On Day 2 of Cycle 1, before your morning dose of study drug, the following tests and
procedures will be performed:

- Blood (about 1 teaspoon) will be drawn for a troponin test.

- Blood (about 4 teaspoons) will be drawn for PK and PD testing.

- Your performance status will be recorded.

- You will be asked about any drugs you may be taking and if you have experienced any
side effects.

On Days 8, 15, 21, and 28 of Cycle 1, the following tests and procedures will be performed:

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

- You will have an ECG.

- Blood (about 3 tablespoons on Days 8 and 15; about 1 tablespoon on Days 21 and 28) and
urine will be collected for routine tests.

- Your performance status will be recorded.

- You will be asked about any drugs you may be taking and if you have experienced any
side effects.

On Day 21 of Cycle 1, blood (about 2 teaspoons each time) will be drawn for PK testing
before the morning dose and then 6 more times over the next 12 hours after the dose. Blood
(about 2 teaspoons each time) will also be drawn for PD testing.

On Day 22 of Cycle 1, before your morning dose of study drug, the following tests and
procedures will be performed:

- Your performance status will be recorded.

- You will be asked about any drugs you may be taking and if you had any side effects
from them.

- Blood (about 2 teaspoons) will be drawn for PK testing before your morning dose of the
study drug.

On Days 1, 15, and 28 of Cycles 2 and beyond, the following tests and procedures will be
performed:

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

- Your performance status will be recorded.

- You will be asked about any drugs you may be taking and if you had any side effects
from them.

- You will have an ECG.

- You will have an echocardiogram or MUGA scan.

- Blood (about 3 tablespoons) will be drawn for routine tests.

- You will be asked about any drugs you may be taking and if you have experienced any
side effects.

- Women who are able to become pregnant will have a urine pregnancy test.

About every 8 weeks, you will have an x-ray, CT scan, or MRI scan to check the status of the
disease.

Length of Study:

You may continue taking the study drug for as long as you are benefitting. You will be taken
off study if the disease gets worse, you experience intolerable side effects, or your doctor
thinks that it is no longer in your best interest to receive the study drug.

You may choose to stop taking the study drug at any time. You should tell the study doctor
right away if you are thinking about stopping your participation in this study. The study
doctor will talk to you about how to safely stop taking the study drug.

End-of-Study Visi:t

Within 14 days after the last dose of study drug, you will return for a final visit. The
following tests and procedures will be performed at the final visit:

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

- You will have an ECG.

- Blood (about 4 tablespoons) and urine will be collected for routine tests.

- You will have either an ECHO or MUGA scan.

- You will have an x-ray, CT scan, or MRI scan to check the status of the disease.

- Your performance status will be recorded.

- You will be asked about any drugs you may be taking and if you have experienced any
side effects.

Follow-Up:

You will be called about 30 days after the last dose of OPB-31121 and asked if you have
experienced any new or ongoing side effects.

This is an investigational study. OPB-31121 is not FDA approved or commercially available.
At this time, OPB-31121 is only being used in research.

Up to 36 patients will take part in this multicenter study. Up to 18 will be enrolled at M.
D. Anderson.


Inclusion Criteria:



1. Subjects with histologically or radiologically confirmed solid tumors refractory to
standard therapy, for which there is no standard therapy, or are not eligible for
standard therapy. Subjects must have at least one measurable lesion.

2. Male and female subjects >/= 18 years of age.

3. Male and female subjects who are surgically sterile; female subjects who have been
postmenopausal for at least 12 consecutive months; or male and female subjects who
agree to remain abstinent or to begin TWO acceptable methods of birth control from
one week prior to drug administration through 30 days (for females) and 90 days (for
males) from the last dose of study medication. If employing birth control, two of the
following precautions must be used: vasectomy, tubal ligation, vaginal diaphragm,
intrauterine device (IUD), condom, diaphragm, cervical cap or sponge with spermicide.

4. Eastern Cooperative Oncology Group (ECOG) performance status:
5. Subjects must have a life expectancy of longer than 3 months.

6. Adequate vital organ function as follows: Neutrophils: >/= 1,500/microliter;
platelets: >/= 75,000/microliter; hemoglobin: >/= 9.0 g/dL; Aspartate transaminase
(AST), Alanine transaminase (ALT): liver metastases. In these cases, AST, ALT bilirubin: < 2.5 * ULN. Subjects must have a normal serum creatinine with a measured
24 hour creatinine clearance of > 60 cc/min; INR < 1.5

7. Ability to provide written informed consent prior to initiation of any study-related
procedures, and ability, in the opinion of the principal investigator, to comply with
all the requirements of the study.

8. Subjects, who have received prior therapy, eg, chemotherapy, radiotherapy, or
surgery, must have stopped therapy for >/= 4 weeks prior to drug administration.
Subjects who have received targeted or immunotherapy must have stopped therapy for 5
half lives or 4 weeks prior to drug administration, whichever is earlier, and
recovered from any prior toxicity not mentioned above to at least Grade 1.

9. Subjects must have a normal ejection fraction (>/= 50%) as measured by either
echocardiogram or multi gated acquisition (MUGA) scan.

Exclusion Criteria:

1. Uncontrolled intercurrent illness including, but not limited to ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

2. Known central nervous system (CNS) metastasis.

3. Presence of active gastrointestinal disease or other condition (eg, significant bowel
resections) which has the potential to significantly affect the absorption of the
study drug, in the opinion of the investigator or sponsor.

4. Known history of or concurrent hepatitis or acquired immunodeficiency syndrome (AIDS)
or known carriers of hepatitis B surface antigen (HBsAg) and/or hepatitis C
antibodies (anti-HCV), or human immunodeficiency virus (HIV) antibodies.

5. Subjects who are pregnant or breast feeding. A negative urine pregnancy test must be
confirmed prior to the first dose of study drug for women of child bearing potential
(WOCBP).

6. Administration of another investigational agent within 28 days or 5 half-lives for
targeted therapy or immunotherapy (whichever is shorter) prior to study entry

7. Use of prohibited medications

8. Subjects with history of coagulopathy (or taking anticoagulants) including deep vein
thrombosis (DVT)/pulmonary embolism (PE), myocardial infarction or stroke within the
last 6 months.

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Maximum Tolerated Dose (MTD) of OPB-31121

Outcome Description:

The MTD is defined as the highest dose level at which < 2 of 6 subjects experience dose limiting toxicity (DLT) during the first cycle.

Outcome Time Frame:

4 Week Cycle

Safety Issue:

Yes

Principal Investigator

David S. Hong, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

2009-0206

NCT ID:

NCT00955812

Start Date:

June 2009

Completion Date:

November 2012

Related Keywords:

  • Advanced Cancer
  • Solid Tumor
  • OPB-31121
  • Advanced Solid Tumor
  • STAT3
  • IL-6-induced STAT3 phosphorylation
  • Neoplasms

Name

Location

UT MD Anderson Cancer CenterHouston, Texas  77030
Sarah Cannon Research Institute (SCRI)Nashville, Tennessee  37203