An Open Label, Phase I, Single Group Assignment Dose Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of TTP607 Administered in Cycles of Five Daily One to Four Hour Infusions to Patients With Advanced Refractory Solid Malignancies
18 Years
N/A
Both
Advanced Cancers, Lymphoma
Trial Information
An Open Label, Phase I, Single Group Assignment Dose Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of TTP607 Administered in Cycles of Five Daily One to Four Hour Infusions to Patients With Advanced Refractory Solid Malignancies
The Study Drug:
TTP607 is designed to work by blocking the action of certain enzymes (proteins) in the blood
that are responsible for abnormal growth of cancer cells. This may cause the cancer cells to
eventually die.
Dose Level Assignment:
If you are found to be eligible to take part in this study, you will be enrolled in a group
of 3-6 participants. The dose you receive will be based on when you join this study (on how
many participants have been enrolled before you, and on the safety data that is available at
that time). The first group of participants will receive the lowest dose of TTP607. Each new
group of participants will receive the next highest dose of the study drug, as long as no
intolerable side effects occur. This process will continue until the highest tolerable dose
of TTP607 is reached. Once the highest tolerable dose is found, 12 additional participants
will be enrolled and treated at that dose, so that researchers can learn more about the
effects of the study drug on the tumor. Both you and your study doctor will know what dose
of the study drug you are receiving.
Study Drug Administration:
Starting on Day 1 of Cycle 1, you will receive TTP607 by central venous catheter (CVC or
central venous line). There are several types of central venous catheters. Each type of
catheter is a flexible, long, thin tube that is inserted through a vein, under a local
anesthetic, through a small cut in your chest (near your heart). Some chemotherapy drugs
are not suitable to be given into the veins in your hand or arm, so these drugs must be
given into a larger vein. The CVC may also be used for drawing blood samples that are needed
regularly. Using the CVC for these blood draws will lower the need for repeated blood draws
from your arm. TTP607 will be given over 1-4 hours depending on the dose you receive, each
day for 5 days in a row, followed by a 10-day "rest period" (no study drug). This 15 days is
considered 1 cycle.
Study Visits:
On Day 1 (All Cycles):
You will have the below tests/procedures during your study visits:
- Your vital signs will be taken.
- You will have blood (about 1-2 tablespoons each time) drawn and urine collected for
routine tests.
- You will be asked about any other medications that you may be taking and any side
effects you may have experienced since your last visit.
- You will have an ECG.
- You will have a brief physical exam and routine eye exam.
- You will have a computed tomography (CT), magnetic resonance imaging (MRI), or positron
emission tomography (PET) scan to check the size of the tumor.
- You will complete a questionnaire (1 question only) to rate your quality of life over
the past week. It should take about 1 minute to complete.
- Women who are able to have children will have a urine pregnancy test.
On Days 2-5 (All Cycles):
The following tests/procedures will be performed before the start of the study drug
infusion:
- You will be asked about any side effects that you may have had since your last visit.
- Your weight will be measured.
After the infusion, your vital signs will be measured.
On Days 2-5 (Cycle 1):
You will have an ECG performed, and blood (about 2-3 teaspoons each time) and urine will be
collected for routine tests.
On Days 8, 10, and 12 (Cycle 1):
You will have the below tests/procedures during your study visits:
- You will complete the questionnaire to rate your quality of life over the past week.
- You will be asked about any medications you may have taken since your last visit and if
you have had any side effects from them.
- You will have an ECG (Day 8 only).
- You will have blood (about 2-3 teaspoons each time) and urine collected for routine
tests.
- You will have a brief physical exam and routine eye exam.
- Your weight will be measured (Days 8 and 12).
- Your vital signs will be measured.
On Days 3 and 5 (Cycles 2 and 3):
You will have an ECG.
On Days 2, 3, and 5 (Cycles 2 and 3):
You will have blood (about 2-3 teaspoons each time) drawn and urine collected for routine
tests.
On Days 8-12 (Cycles 2, 3, and Further Cycles):
At least once at some time between Days 8 and 12, you will return to the clinic for the
following tests/procedures:
- You will complete the questionnaire to rate your quality of life over the past week (on
Day 12 of even-numbered cycles).
- You will be asked about any medications you may have taken since your last visit and if
you have had any side effects from them.
- You will have an ECG (Cycles 2 and 3).
- You will have blood (about 2-3 teaspoons each time) and urine collected for routine
tests.
- You will have a brief physical exam and routine eye exam.
- Your weight and vital signs will be measured.
On Day 5 (Cycle 4 and Further Cycles):
You will have blood (about 2-3 teaspoons each time) and urine collected for routine tests.
PK Testing:
You will have blood (about 2-3 teaspoons each time) and urine samples collected at different
times for PK testing of TTP607.
Cycle 1:
Days 1 and 5:
Blood will be drawn immediately before the infusion, at 30 minutes during the infusion, at
60 minutes immediately after the infusion, and at 15 minutes, 30 minutes, 45 minutes, and at
1, 2, 3, 4, and 6 hours after the infusion.
On Day 1, urine will be collected immediately before the infusion and within 3 hours,
between 3 and 7 hours, between 7 and 12 hours, and between 12 and 24 hours after the
infusion. On Day 5, urine will be collected before the infusion and within 3 hours and
between 3 and 7 hours after the infusion.
Days 2, 3, and 4:
Blood will be drawn immediately before the infusion and at 1 hour after the end of the
infusion. Urine will be collected immediately before the infusion and within 2 hours after
the end of the infusion.
Day 8:
Blood will be drawn at any convenient time, and urine will be collected when you first
arrive in the clinic.
Cycles 2 and 3:
Days 1 and 5:
Blood will be drawn before the infusion and at 1 and 2 hours after the infusion, and urine
will be collected before the infusion and within 2 hours after infusion.
Days 8-12:
Blood will be drawn at any convenient time, and urine will be collected when you first
arrive in the clinic.
Cycle 4 and Further Cycles:
Day 5:
Blood will be drawn 1 hour after the infusion, and urine will be collected immediately
before the infusion and within 2 hours after the infusion.
Length of Study:
You will continue on this study, as long as the study doctor thinks it is safe to continue,
the cancer does not get worse, and if no intolerable side effects occur. If you continue on
to further cycles, you will be on the same study drug schedule and will have the same
tests/procedures for study visits, though they may be performed less often.
End-of-Study Visit:
Once you are off this study for any reason, you will have an end-of-study visit about 30
days after your last dose of the study drug. During this visit, you will have the following
tests/procedures:
- You will have a complete physical exam, including measurement of your vital signs.
- Your blood (about 2 teaspoons) will be drawn and urine collected for routine tests.
- You will have an ECG.
- You will complete the questionnaire to rate your quality of life over the past week.
- Women who are able to have children will have a blood (about 1 teaspoon) pregnancy
test.
This is an investigational study. TTP607 is not FDA approved or commercially available. At
this time, it is being used for research purposes only. Up to 40 patients will take part in
this study. All will be enrolled at M. D. Anderson.
Inclusion Criteria:
Inclusion:
1. Patients with pathologically confirmed advanced malignancy that is metastatic or
unresectable and which is refractory to standard therapy or for which there is no
standard therapy.
2. Measurable disease at baseline.
3. At least four weeks since the last dose of prior chemotherapy, radiation therapy, or
investigational agents, six weeks if the last regimen included BCNU or mitomycin C,
six weeks if the agent was an antibody, four weeks if a chimeric antibody. For
targeted therapies such as Gleevec®, Tarceva®, Nexavar®, Iressa®, or Sutent® at least
five half-lives need to have elapsed since the last dose. Patients must be recovered
from the adverse effects of prior therapy at the time of enrollment.
4. Age >/=18 years, male or female patients.
5. Women of child-bearing potential or men whose sexual partners are women of
child-bearing potential must agree to use two methods of adequate contraception
(i.e., hormonal and barrier method of birth control) prior to study entry, for the
duration of the study, and for 30 days after the last dose of study medication.
6. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.
7. Patients must have normal organ and marrow function as defined: leukocytes >/=
3,000/mcL; absolute neutrophil count >/=1,500/mcL; platelets >/= 100,000/mcL; total
bilirubin creatinine
8. Patients must have an existing patent and viable central venous catheter, or have
such a line inserted within 28 days prior to initiation of study drug.
9. Patients must be able to understand and willing to sign a written informed consent
document and have the capacity to follow study instructions.
Exclusion Criteria:
1. Uncontrolled concurrent illness, including but not limited to: ongoing or active
infection, symptomatic congestive heart failure (NYHA Class III or IV), unstable
angina pectoris, life-threatening cardiac arrhythmia, or psychiatric illness/social
situations that would limit compliance with study requirements and/or obscure study
results. Patients with a history of myocardial infarction in the last three months
are also excluded from the trial.
2. Patients with known brain metastases that are symptomatic
3. Patients with leukemias or myelodysplastic syndrome (MDS).
4. Patients who have undergone bone marrow or stem cell transplantation within the last
5 years.
5. A requirement, as judged by the Principal Investigator, for primary prophylaxis with
colony stimulating factors based on an expectation by the investigator of a risk of
febrile neutropenia of 20% or greater or clinical factors that predispose the patient
to increased complications from prolonged neutropenia as discussed in the latest
American Society of Clinical Oncology (ASCO) recommendations for the use of white
blood cell growth factor guidelines.
6. Nursing or pregnant women.
7. Documented HIV, HBV or HCV infection.
8. Patients with hypersensitivity to compounds of similar chemical or biologic
composition to TTP607 or constituents of the intravenous (i.v.) formulation.
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
Outcome Time Frame:
End of each 15 day cycle
Safety Issue:
Yes
Principal Investigator
Jennifer J. Wheler, MD
Investigator Role:
Study Chair
Investigator Affiliation:
UT MD Anderson Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
2007-0219
NCT ID:
NCT00939172
Start Date:
March 2010
Completion Date:
Related Keywords:
- Advanced Cancers
- Lymphoma
- Advanced Refractory Solid Malignancies
- Solid tumor
- Lymphoma
- TTP607
- Neoplasms
- Lymphoma
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