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A Multi-Arm Complete Phase 1 Trial of Valproic Acid-Based 2-Agent Oral Regimens for Patients With Advanced Solid Tumor

Phase 1
Not Enrolling
Solid Tumors

Thank you

Trial Information

A Multi-Arm Complete Phase 1 Trial of Valproic Acid-Based 2-Agent Oral Regimens for Patients With Advanced Solid Tumor

The Study Drugs:

Valproic acid is designed for use as an anti-seizure medication. It is thought to also have
anticancer activity by activating ("turning on") tumor-fighting genes, which may cause
cancer cell death.

Dasatinib is designed to change the function of genes. By changing the function of these
genes, it may prevent cancer from growing and spreading.

Erlotinib hydrochloride is designed to block the activity of a protein found on the surface
of many tumor cells that may control tumor growth and survival. This may stop tumors from

Lapatinib is designed to block the activity of certain molecules. These molecules play a
part in the growth of cancer cells and are particularly important for the growth of
inflammatory breast cancer tumors.

Lenalidomide is designed to change the body's immune system. It may also interfere with the
development of tiny blood vessels that help support tumor growth. Therefore, in theory, it
may decrease or prevent the growth of cancer cells.

Sorafenib is designed to block the function of a cancer protein as well as tumor
blood-vessel forming proteins.

Sunitinib malate is designed to block pathways that control important events such as the
growth of blood vessels that are essential for the growth of cancer.

Study Administration:

If you are found to be eligible to take part in this study, the study doctor will decide
which drug you will receive with valproic acid, based upon your particular disease. You will
then begin taking valproic acid plus either dasatinib, erlotinib hydrochloride, lapatinib,
lenalidomide, sorafenib, or sunitinib malate. One (1) cycle is either 21 or 28 days long,
depending on which study drug combination you receive.

You will take valproic acid by mouth once or twice a day for 7 days in a row. You will then
have a 7-day "rest" period from taking this drug.

You will also take either sorafenib or sunitinib malate by mouth once or twice a day
continuously for 21 days, or dasatinib, erlotinib hydrochloride, lapatinib, or lenalidomide
by mouth once or twice a day continuously for 28 days.

Depending on what stage of the study you are in, you will take the study drugs either once
or twice a day.

Study Visits:

You will have the below tests/procedures at designated study visits.

Before each cycle (within 7 days of after your last dose)

- You will be have a complete physical exam.

- Your performance status will be recorded.

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

- If you are able to become pregnant, you will have a blood (about 1 teaspoon) or urine
pregnancy test. To take part in this study, you must not be pregnant.

After the end of Cycles 2, 4 and 6, you will have a chest x-ray and either a CT scan, MRI
scan, or PET scan to check the status of the cancer. You will then have a chest x-ray and
either a CT scan, MRI scan, or PET scan after the end of every 3 cycles (Cycle 9, 12, 15,
and so on) to check the status of the cancer.

Length of Study:

You will continue to take your study drug combination on this study, as long as the disease
does not get worse and you do not experience any intolerable side effects.

End-of-Study Visit:

Once you have stopped taking your study drug combination, you will come back for an
end-of-study visit to have the following tests/procedures performed:

- You will have a complete physical exam.

- Your performance status will be recorded.

- Blood may be drawn (about 1 tablespoon) for routine tests

- You may have a CT scan, an MRI scan, or PET to check the status of the cancer,
depending on what the study doctor thinks is necessary.


The status of the disease will be followed-up for as long as possible after you complete
this study. Once every 8 weeks, you will either be contacted by phone and asked how you are
feeling (which should take about 5-10 minutes), or you will be asked to come to the clinic
for a routine visit. You will have a CT or MRI scan once every 12 weeks (or until another
anticancer therapy has been started) to check the status of the cancer.

This is an investigational study. Each of the study drugs is FDA approved and commercially
available. The combination of valproic acid plus one of the other study drugs is
investigational in this study.

Valproic acid is FDA approved for the treatment of simple and complex absence seizure,
complex partial epileptic seizure, acute mania, and migraine prophylaxis.

Dasatinib is FDA approved for the treatment of acute lymphoid leukemia (ALL) and chronic
myeloid leukemia (CML).

Erlotinib hydrochloride is FDA approved for the treatment of carcinoma of the pancreas and
non-small-cell lung cancer.

Lapatinib is FDA approved for the treatment of breast cancer (inflammatory, relapsed, or
refractory) and metastatic breast cancer (HER2 overexpression).

Lenalidomide is FDA approved for the treatment of multiple myeloma and myelodysplastic

Sorafenib is FDA approved for the treatment of renal cell carcinoma. Sunitinib malate is FDA
approved for the treatment of gastrointestinal stromal tumors and renal cell carcinoma.

Up to 327 patients will take part in this study. All will be enrolled at M. D. Anderson.

Inclusion Criteria:

1. Patients must have advanced solid tumor: they have either a disease where there is no
established standard of care therapy or have failed one or more prior therapy. (for
all treatment arms)

2. Patients must have ECOG performance status < or = 2 (0-2). Patients modified Lansky scale >/= 60. Patients >10 to 18 years Karnovsky scale >/= 60.(for
all treatment arms)

3. Patients must have normal organ and marrow function as defined below: Platelets >
50,000/uL; Creatinine clearance > 20mL/min (for all treatment arms); Total bilirubin
< 5 mg/dL (except for Lapatinib arm); ALT
4. (cont. from above) Liver function criteria and dosing based on each individual drug:
Valproic acid - if ALT >/= 6X ULN or T. Bili >/= 3, then dose should be decreased by
50%; Sorafenib - If Child Pugh class A or B, no dose adjustment; if Child Pugh class
C, decrease dose by 50% (400 mg po daily max); Sunitinib - If ALT >/= 6X ULN or T.
Bili >/= 3 , decrease dose by 25% (37.5 mg po daily max);

5. (cont. from above) Erlotinib - If ALT > 6X ULN or T. Bili >/= 3 , decrease dose by
25% (100 mg po daily max); Lapatinib - If ALT > 3X ULN or T. Bili > 2X ULN, decrease
dose by 60% (500-750 mg po daily max); Dasatinib - No dose adjustment needed;
Lenalidomide - No dose adjustment needed.

6. Patients or legal representative must be able to understand and be willing to sign an
IRB-approved written informed consent document. (for all treatment arms)

7. Women of child-bearing potential and men must agree to use adequate contraception
prior to study entry, for the duration of study participation, and for 30 days after
the last dose. (for all treatment arms)

Exclusion Criteria:

1. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure (NYHA Class III or IV), unstable
angina pectoris, symptomatic cardiac arrhythmia, active bleeding, active thrombosis,
or psychiatric illness/social situations that would limit compliance with study

2. History of allergic reactions to the study drugs or their analogs.

3. Failure to recover from any prior surgery within 4 weeks of study entry.

4. Any treatment specific for tumor control within 3 weeks of study drugs; or within 2
weeks if cytotoxic agents were given weekly (within 6 weeks for nitrosoureas or
mitomycin C), or within 4 half-lives for target agents with half lives and
pharmacodynamic effects lasting less than 5 days (that include but are not limited to
erlotinib, sorafenib, sunitinib, bortezomib, and other similar agents); or failure to
recover from the toxic effect of any therapy prior to study entry.

5. Study agents cannot be obtained for any reason since this study does not provide free

6. Any prior history of hypertensive crisis or hypertensive encephalopathy.

7. Significant vascular disease (e.g., aortic aneurysm, aortic dissection) and
symptomatic peripheral vascular disease

8. Evidence of bleeding diathesis or coagulopathy.

9. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to study enrollment or anticipation of need for major surgical procedure during
the course of the study.

10. Minor surgical procedure, excluding placement of a vascular access device, within 7
days prior to study enrollment.

11. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 6 months prior to study enrollment; and serious, non-healing wound,
ulcer, or bone fracture.

Type of Study:


Study Design:

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

Outcome Measure:

Maximum Tolerated Dose (MTD) as Determined by the Number of Participants With Dose Limiting Toxicities

Outcome Time Frame:

At Day 28 (1 Cycle)

Safety Issue:


Principal Investigator

Aung Naing, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Institutional Review Board

Study ID:




Start Date:

June 2007

Completion Date:

Related Keywords:

  • Solid Tumors
  • Solid Tumors
  • Advanced Cancer
  • Dasatinib
  • Erlotinib
  • Lapatinib
  • Lenalidomide
  • Sorafenib
  • Erlotinib Hydrochloride
  • Sunitinib Malate
  • Sunitinib
  • Valproic Acid
  • SU011248
  • Neoplasms



UT MD Anderson Cancer CenterHouston, Texas  77030