AzTrials
AzTrials

Malignant MelanomaPhase 1/2NCT00358319

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

A Phase 1/2 study testing Karenitecin and Valproic Acid in people with Malignant Melanoma, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Malignant Melanoma
What is being tested?
Karenitecin and Valproic Acid
Could I receive a placebo?
No, everyone receives an active treatment
How many people
42 participants
Where
1 siteUnited States
Study dates
Mar 2005to Apr 2007
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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)
Show all 13Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • H. Lee Moffitt Cancer Center & Research Institute

    Tampa, Florida, 33612

Other trials in United States

About this study

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

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.

Read the detailed description

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.

Being tested
Karenitecin, Valproic Acid
Keywords
Valproic Acid (VPA), Karenitecin, Malignant Melanoma, Histone deacetylases (HDAC)inhibitors, Topoisomerase I inhibitor, metastatic
Medical subject headings
Melanoma, Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • KarenitecinDrug

  • Valproic AcidDrug

    Also called VPA

Study groups in NCT00358319
Study groupRoleWhat they receive
Phase IExperimentalDose escalation phase
Receives: Drug: Karenitecin; Drug: Valproic Acid
Phase IIExperimentalAll 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.
Receives: Drug: Karenitecin; Drug: Valproic Acid

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety profile of Valproic Acid (VPA) and Karenitecin

    Measured: Average of 6 months

  2. Maximum tolerated dose (MTD) of Valproic Acid and Karenitecin

    Measured: Average of 6 months

  3. Response rate

    Measured: Average of 6 months

  4. Time to progression (TTP)

    Measured: Average of 6 months

  5. Overall survival (OS)

    Measured: Average of 6 months

Secondary outcomes (3)

  1. Pharmacokinetic parameters of VPA and Karenitecin

    Measured: Average of 6 months

  2. Relationship between topo I expression, location and DNA strand breakage

    Measured: Average of 6 months

  3. Patient response to this drug combination

    Measured: Average of 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Jul 2006 (estimated)
  2. Study startMar 2005
  3. Primary completionApr 2007
  4. Study completionApr 2007

Why it stopped: PI left Moffitt

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
42 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00358319
Sponsor's protocol ID
MCC-13991
Status last verified
Feb 2011
First submitted
27 Jul 2006
Last updated
25 Nov 2013
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Karenitecin and Valproic Acid in people with Malignant Melanoma, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 25 Nov 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: PI left Moffitt). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety profile of Valproic Acid (VPA) and Karenitecin (time frame: Average of 6 months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00358319.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Nov 2013.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in