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

NCT00358319 | Terminated Phase 1 DMC

• 1 other identifier: MCC-13991
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase I study looking at the combination of Valproic Acid (VPA) and Karenitecin to treat patients with metastatic malignant melanoma. We will find the dose-limiting toxicity (DLT) and the highest dose (maximum tolerated dose) of this combination treatment that has acceptable side effects and recommend a Phase II dose level. There will be seven escalating doses of Valproic acid and one dose escalation step of Karenitecin. Each patient shall receive one cycle of Karenitecin alone (cycle 1 days 1 - 5) followed by the same dose of Karenitecin given in combination with VPA (cycle 2 days 1-7). Patients will receive oral VPA in divided doses for 5 days and Karenitecin starting on the 3rd day every 3 weeks (a treatment cycle). Treatment will continue until progression of disease or an unacceptable level of toxicity. After 2 cycles of treatment there will be the first efficacy evaluation or restaging of the disease. In the absence of disease progression and if there is continued safety and tolerability, treatment may continue.

Conditions

Malignant Melanoma

Keywords

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

Outcome Measures

Primary Outcomes (5)

• Safety profile of Valproic Acid (VPA) and Karenitecin

  Average of 6 months

• Maximum tolerated dose (MTD) of Valproic Acid and Karenitecin

  Average of 6 months

• Response rate

  Average of 6 months

• Time to progression (TTP)

  Average of 6 months

• Overall survival (OS)

  Average of 6 months

Secondary Outcomes (3)

• Pharmacokinetic parameters of VPA and Karenitecin

  Average of 6 months

• Relationship between topo I expression, location and DNA strand breakage

  Average of 6 months

• Patient response to this drug combination

  Average of 6 months

Study Arms (2)

Phase I

EXPERIMENTAL

Dose escalation phase

Drug: Karenitecin; Drug: Valproic Acid

Phase II

EXPERIMENTAL

All patients enrolled in the Phase II will be treated with Valproic Acid (VPA) and Karenitecin using the dosing schedule determined to be the Maximum Tolerated Dose (MTD) in Phase I.

Drug: Karenitecin; Drug: Valproic Acid

Interventions

Karenitecin DRUG

Phase I; Phase II

Valproic Acid DRUG

Also known as: VPA

Phase I; Phase II

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• BioNumerik Pharmaceuticals, Inc.: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

MeSH Terms

Conditions

Melanoma; Neoplasm Metastasis

Interventions

cositecan; Valproic Acid

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids

Study Officials

• Adil Daud, M.D.

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: July 27, 2006
• First Posted: July 31, 2006
• Study Start: March 1, 2005
• Primary Completion: April 1, 2007
• Study Completion: April 1, 2007
• Last Updated: November 25, 2013

Record last verified: 2011-02

Locations

US (1)