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Phase I/II Trial of Valproic Acid and Karenitecin for Metastatic Malignant Melanoma


Phase 1/Phase 2
18 Years
N/A
Not Enrolling
Both
Malignant Melanoma

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Trial Information

Phase I/II Trial of Valproic Acid and Karenitecin for Metastatic Malignant Melanoma


Treatment cycles are every 3 weeks and there are 17 study visits in all.

During Phase I subjects will receive one cycle of Karenitecin alone (cycle 1 days 1-5) and
then combination therapy with VPA + Karenitecin (cycle 2 days 1-7)followed by oral VPA in
divided doses for 5 days and Karenitecin starting the third day (days 3-7) every 3 weeks.
After 2 cycles of treatment there will be the first efficacy evaluation or restaging of the
disease.

Dose escalations will continue until unacceptable dose limiting toxicity (DLT) occurs, then
dose escalation will be stopped and the previous dose level will be explored. In each dose
level, participants will undergo pharmacokinetic (PK) sampling to determine blood levels.
The melanoma skin lesions will also be biopsied to measure the effect of the combination
therapy.

All patients enrolled in the Phase II will be treated with VPA and Karenitecin using the
dosing schedule determined to be the MTD in Phase I. In the absence of disease progression
and if there is continued safety and tolerability, treatment may continue in consecutive 3
week cycles.


Inclusion Criteria:



Same for Phase I & II

- Cytologically/histologically-documented metastatic (stage IV) malignant melanoma

- Age greater than or equal to 18 years old

- ECOG performance status 0-2

- Subjects must be able to give informed consent and be able to follow the guidelines
given in the study

- The subject has no major impairment of hematological function, as defined by the
following laboratory parameters: WBC > 3.0x109/L; ANC > 1.5 x 109/L; Hgb > 9.0g/dL;
PLT >100x109/L. Red blood cell transfusions and repeat evaluations for study entry
are allowed

- All subjects of reproductive potential must use an effective method of contraception
during the study and three months following termination of treatment (Not applicable
to patients with bilateral oophorectomy and/or hysterectomy or to those patients who
are postmenopausal.)

- Subjects with biopsiable disease are preferred but not mandatory; subjects with
biopsiable disease will be encouraged to undergo biopsy.

Exclusion Criteria:

Phase I:

- Subjects must not have evidence of significant active infection (e.g., pneumonia,
cellulitis, wound abscess, etc.) at time of study entry.

- Subjects must have adequate renal and normal hepatic function (creatinine < 1.5 x
upper limit of normal (ULN), bilirubin and SGOT (AST) < 1.5 X ULN) obtained within 4
weeks prior to registration.

- Pregnant women are excluded from the study because VPA is known to cause birth
defects. Nursing mothers are excluded from this trial as effects on newborns and
excretion of either drug in milk is unknown.

- Women of childbearing age must have a negative pregnancy test and be willing to use a
highly effective method of contraception. Men who are sexually active must also be
willing to use an accepted and effective method of contraception.

- Subjects with uncontrolled CNS metastasis or a history of seizures are excluded.
Subjects with stable CNS metastasis (either surgically resected, treated with the
gamma knife or stable for 3 months following whole brain radiotherapy are eligible)

Phase II:

- Subjects must not have evidence of significant active infection (e.g., pneumonia,
cellulitis, wound abscess, etc.) at time of study entry.

- Subjects must have adequate renal and normal hepatic function (creatinine < 1.5 x
upper limit of normal (ULN), bilirubin and SGOT (AST) < 1.5 X ULN) obtained within 4
weeks prior to registration.

- Pregnant women are excluded from the study because VPA is known to cause birth
defects. Nursing mothers are excluded from this trial as effects on newborns and
excretion of either drug in milk is unknown.

- Women of childbearing age must have a negative pregnancy test and be willing to use a
highly effective method of contraception. Men who are sexually active must also be
willing to use an accepted and effective method of contraception.

- Subjects with uncontrolled CNS metastasis or a history of seizures are excluded.
Subjects with stable CNS metastasis (either surgically resected, treated with the
gamma knife or stable for 3 months following whole brain radiotherapy are eligible)

- Subjects who have been previously treated with more than 2 prior chemotherapy
regimens. Any previous immunotherapy regimens are allowed.

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:

Safety profile of Valproic Acid (VPA) and Karenitecin

Outcome Time Frame:

Average of 6 months

Safety Issue:

Yes

Principal Investigator

Adil Daud, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

UCSF (formerly at H. Lee Moffitt Cancer Center & Research Institute)

Authority:

United States: Food and Drug Administration

Study ID:

MCC-13991

NCT ID:

NCT00358319

Start Date:

March 2005

Completion Date:

April 2007

Related Keywords:

  • Malignant Melanoma
  • Valproic Acid (VPA)
  • Karenitecin
  • Malignant Melanoma
  • Histone deacetylases (HDAC)inhibitors
  • Topoisomerase I inhibitor
  • metastatic
  • Melanoma

Name

Location

H. Lee Moffitt Cancer Center & Research InstituteTampa, Florida  33612