Malignant MelanomaPhase 1/2UPCI-07-008NCT00715793
Combination of Decitabine and Temozolomide in the Treatment of Patients With Metastatic Melanoma
A Phase 1/2 study testing Decitabine, Temozolomide and biopsy in people with Malignant Melanoma, run by Hussein Tawbi at 1 site in United States.
Trial summary
The combination of TMZ and DAC may effect dual modulation of DNA repair genes resulting in improved clinical response. 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?
- Decitabine, Temozolomide and biopsy
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2008to Aug 2015
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Patients who have non-resectable Stage IIIB or stage IV metastatic melanoma that have progressed despite prior therapies.
- Life expectancy of at least 12 weeks.
- ECOG performance status of 0, 1 and 2.
- ≥18 years of age.
- Patients who have not received any other chemotherapeutic, biological or investigational agent within 28 days of study drug administration.
- First line and active brain metastases (metastatic lesions to the brain that have been adequately treated with surgery and/or appropriate radiation therapy and that have documented stability for >4 weeks or >2 weeks if treated with stereotactic radiosurgery, remain eligible)
Who cannot join
- Any evidence of renal dysfunction (proteinuria, estimated creatinine clearance from serum creatinine test of <60 ml/min).
- Impaired hepatic function (liver enzymes greater than twice the upper limit of normal or bilirubin > 2.0 except in patients with Gilbert's syndrome).
- Prior treatment with alkylating agents (including TMZ and DTIC).
- Active brain metastases (metastatic lesions to the brain that have been adequately treated with surgery and/or appropriate radiation therapy and that have documented stability for >4 weeks remain eligible).
- Active infections or serious general medical conditions.
- Female patients of child-bearing age who are not on adequate contraception, or are pregnant or breast-feeding.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I/II Trial of the Combination of Decitabine and Temozolomide in the Treatment of Patients With Metastatic Melanoma
The combination of TMZ and DAC may effect dual modulation of DNA repair genes resulting in improved clinical response.
Read the detailed description
Primary Objectives:
- Phase I: To determine the safety, tolerability, and Phase II recommended dose of the combination of extended schedule TMZ and DAC.
- Phase II: To determine the efficacy, as measured by overall response rate, of the combination of extended schedule TMZ and DAC given at the Phase II recommended dose to patients with metastatic melanoma.
Secondary Objectives:
- To determine pharmacokinetics of the combination of TMZ and DAC in patients with metastatic melanoma.
- To determine, in peripheral blood mononuclear cells (PBMC) and tumor tissue, the pharmacodynamic effects of the combination of TMZ and DAC on promoter methylation and expression of selected genes and correlate these with response.
- To determine the progression-free survival of patients treated with the combination of TMZ and DAC.
- Conditions
- Malignant Melanoma
- Being tested
- Decitabine, Temozolomide, biopsy
- Keywords
- Decitabine, Temozolomide, Metastatic, Melanoma, Non-resectable, Stage IIIB melanoma, stage IV melanoma, TMZ, DTIC, promoter methylation, skin cancer, chemotherapy
- Medical subject headings
- Melanoma, Neoplasm Metastasis, Skin Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DecitabineDrug
Also called DTIC
In Part I patients will be treated on a standard "3+3" phase I dose-escalation design starting at 0.075 mg/kg until a decitabine dose level of 0.15 mg/kg is reached, or, in case unacceptable toxicities are observed, at the maximum tolerated dose (Phase II recommended dose). Decitabine will be administered at the specified dose level, intravenously, daily 5 days a week for the first 2 weeks of a 6-week cycle.
TemozolomideDrug
Also called TMZ
Temozolomide is available in 25 mg and 100 mg tablets that will be administered orally; doses will be rounded to the nearest 25 mg. Temozolomide will be administered orally at 75 mg/m2 daily for 4 weeks starting on week 2 of a 6-week cycle.
biopsyProcedure or surgery
Also called fine needle aspirate, FNA, core biopsy
Fine needle aspirates (FNA) and/or core biopsies of tumor samples will be obtained from consenting patients with accessible, evaluable disease, on days 1, 8, 15, and 29 of the first cycle and when patients go off study. Biopsies are optional in Phase I and required for all consenting subjects in Phase II.
| Study group | Role | What they receive |
|---|---|---|
| Single Arm | Experimental | Not described Receives: Drug: Decitabine; Drug: Temozolomide; Procedure: biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants That Experienced a Dose Limiting Toxicity (DLT)
Dose-limiting toxicities (DLTs) were defined as grade 4 neutropenia or thrombocytopenia which lasts >7 days; grade 3 or 4 febrile neutropenia; grade 3 or greater non-hematological toxic effects.
Measured: Up to 26 months
Overall Response Rate (ORR)
Using RECIST v1.0 criteria, overall response rate (ORR) was determined by the number of participants with complete response (CR) + the number of participants with partial response (PR) / the number of participants with complete response (CR) + the number of participants with partial response (PR) + the number of participants with stable disease (SD) + the number of participants with progressive disease (PD), multiplied by 100. Per RECIST v1.0 criteria (assessed by MRI or CT): Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response (PR) nor sufficient increase to to qualify for Progressive Disease (PD); PD, 20% increase in the sum if target lesion or the appearance of new lesions; Complete Response (CR), Disappearance of all target lesions.
Measured: Up to 30 months
Recommended Phase 2 Dose (RP2D) of DAC + TMZ
Toxicity assessments used CTCAE v3.0. Two dose levels were explored in the phase I portion of the study. A modified 3 + 3 'up and down' design was used. Given the knowledge that DAC exhibits its epigenetic effects at 30-fold lower doses than at its maximum-tolerated dose (MTD), escalation of DAC to the MTD was not done.
Measured: Up to 26 months
Secondary outcomes (5)
Disease Control Rate (DCR)
Using RECIST v1.0 criteria, disease control rate (DCR) was determined by the number of participants with complete response (CR) + the number of participants with partial response (PR) + the number of participants with stable disease (SD) / the number of participants with complete response (CR) + the number of participants with partial response (PR) + the number of participants with stable disease (SD) + the number of participants with progressive disease (PD). Per RECIST v1.0 criteria (assessed by MRI or CT): Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response (PR) nor sufficient increase to to qualify for Progressive Disease (PD); PD, 20% increase in the sum if target lesion or the appearance of new lesions; Complete Response (CR), Disappearance of all target lesions.
Measured: Up to 30 months
Progression-free Survival (PFS)
PFS was defined as the time from study entry until the documented radiological or symptomatic progression. Per RECIST v1.0 criteria (assessed by MRI or CT): Progressive Disease (PD); PD, 20% increase in the sum if target lesion or the appearance of new lesions.
Measured: Up to 42 months
6-month Progression-free Survival (PFS) Rate
Measured: 6 months
Overall Survival (OS)
OS was defined as the time from study entry until the death or date of last contract.
Measured: Up to 42 months
1-year Overall Survival (OS) Rate
Percentage of patients alive at one year (number of patients alive / total number of evaluable (analyzed) patients).
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2008 (estimated)
- Study startJun 2008
- Primary completionMay 2015
- Study completionAug 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Malignant MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hussein Tawbi
- Sponsor type
- University, hospital or other
- Collaborators
- Eisai Inc., Schering-Plough
- Responsible party
- Sponsor-investigator, Hussein Tawbi, University of Pittsburgh
- Investigators
- Hussein Tawbi, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00715793
- Sponsor's protocol ID
- UPCI 07-008
- Acronym
- UPCI-07-008
- Status last verified
- Sep 2017
- First submitted
- 27 Jun 2008
- Last updated
- 3 Oct 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Trial of the Combination of Decitabine and Temozolomide in the Treatment of Patients With Metastatic Melanoma
- ClinicalTrials.gov ID
- NCT00715793
- Acronym / sponsor ID
- UPCI-07-008 / UPCI 07-008
- Conditions
- Malignant Melanoma
- Keywords
- Decitabine, Temozolomide, Metastatic, Melanoma, Non-resectable, Stage IIIB melanoma, stage IV melanoma, TMZ
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- Hussein TawbiUniversity, hospital or other
- Collaborators
- Eisai Inc., Schering-Plough
- Study start
- Jun 2008
- Primary completion
- May 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 15 Jul 2008 (estimated)
- Results
- Posted 3 Oct 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The combination of TMZ and DAC may effect dual modulation of DNA repair genes resulting in improved clinical response.
Detailed description
Primary Objectives:
- Phase I: To determine the safety, tolerability, and Phase II recommended dose of the combination of extended schedule TMZ and DAC.
- Phase II: To determine the efficacy, as measured by overall response rate, of the combination of extended schedule TMZ and DAC given at the Phase II recommended dose to patients with metastatic melanoma.
Secondary Objectives:
- To determine pharmacokinetics of the combination of TMZ and DAC in patients with metastatic melanoma.
- To determine, in peripheral blood mononuclear cells (PBMC) and tumor tissue, the pharmacodynamic effects of the combination of TMZ and DAC on promoter methylation and expression of selected genes and correlate these with response.
- To determine the progression-free survival of patients treated with the combination of TMZ and DAC.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single Arm | Experimental | Drug: Decitabine, Drug: Temozolomide, Procedure: biopsy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients who have non-resectable Stage IIIB or stage IV metastatic melanoma that have progressed despite prior therapies.
- Life expectancy of at least 12 weeks.
- ECOG performance status of 0, 1 and 2.
- ≥18 years of age.
- Patients who have not received any other chemotherapeutic, biological or investigational agent within 28 days of study drug administration.
Key exclusion criteria (6 listed)
- Any evidence of renal dysfunction (proteinuria, estimated creatinine clearance from serum creatinine test of <60 ml/min).
- Impaired hepatic function (liver enzymes greater than twice the upper limit of normal or bilirubin > 2.0 except in patients with Gilbert's syndrome).
- Prior treatment with alkylating agents (including TMZ and DTIC).
- Active brain metastases (metastatic lesions to the brain that have been adequately treated with surgery and/or appropriate radiation therapy and that have documented stability for >4 weeks remain eligible).
- Active infections or serious general medical conditions.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DecitabineAlso: DTICIn Part I patients will be treated on a standard "3+3" phase I dose-escalation design starting at 0.075 mg/kg until a decitabine dose level of 0.15 mg/kg is reached, or, in case unacceptable toxicities are observed, at the maximum tolerated dose (Phase II recommended dose). Decitabine will be administered at the specified dose level, intravenously, daily 5 days a week for the first 2 weeks of a 6-week cycle. | Drug | Single Arm |
| TemozolomideAlso: TMZTemozolomide is available in 25 mg and 100 mg tablets that will be administered orally; doses will be rounded to the nearest 25 mg. Temozolomide will be administered orally at 75 mg/m2 daily for 4 weeks starting on week 2 of a 6-week cycle. | Drug | Single Arm |
| biopsyAlso: fine needle aspirate, FNA, core biopsyFine needle aspirates (FNA) and/or core biopsies of tumor samples will be obtained from consenting patients with accessible, evaluable disease, on days 1, 8, 15, and 29 of the first cycle and when patients go off study. Biopsies are optional in Phase I and required for all consenting subjects in Phase II. | Procedure or surgery | Single Arm |
Primary outcome
Percentage of Participants That Experienced a Dose Limiting Toxicity (DLT)
Time frame: Up to 26 months
Dose-limiting toxicities (DLTs) were defined as grade 4 neutropenia or thrombocytopenia which lasts >7 days; grade 3 or 4 febrile neutropenia; grade 3 or greater non-hematological toxic effects.
Overall Response Rate (ORR)
Time frame: Up to 30 months
Using RECIST v1.0 criteria, overall response rate (ORR) was determined by the number of participants with complete response (CR) + the number of participants with partial response (PR) / the number of participants with complete response (CR) + the number of participants with partial response (PR) + the number of participants with stable disease (SD) + the number of participants with progressive disease (PD), multiplied by 100. Per RECIST v1.0 criteria (assessed by MRI or CT): Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response (PR) nor sufficient increase to to qualify for Progressive Disease (PD); PD, 20% increase in the sum if target lesion or the appearance of new lesions; Complete Response (CR), Disappearance of all target lesions.
Recommended Phase 2 Dose (RP2D) of DAC + TMZ
Time frame: Up to 26 months
Toxicity assessments used CTCAE v3.0. Two dose levels were explored in the phase I portion of the study. A modified 3 + 3 'up and down' design was used. Given the knowledge that DAC exhibits its epigenetic effects at 30-fold lower doses than at its maximum-tolerated dose (MTD), escalation of DAC to the MTD was not done.
5 secondary outcomes
Disease Control Rate (DCR)
Time frame: Up to 30 months
Progression-free Survival (PFS)
Time frame: Up to 42 months
6-month Progression-free Survival (PFS) Rate
Time frame: 6 months
Overall Survival (OS)
Time frame: Up to 42 months
1-year Overall Survival (OS) Rate
Time frame: 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Oct 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Malignant Melanoma
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingPhase 1
IL-17 Blockade to Decrease irAEs (REPLAY)
Metastatic Melanoma
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 1
A Feasibility Study Utilizing Immune Recall to Increase Response to Checkpoint Therapy
Melanoma
Active, not recruitingPhase 1/2
A Study of Dapansutrile Plus Pembrolizumab in Patients With PD-1 Refractory Advanced Melanoma
Melanoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hussein Tawbi, MD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Decitabine, Temozolomide and biopsy in people with Malignant Melanoma, run by Hussein Tawbi 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 6 inclusion and 6 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: finished, as of the sponsor's last update on 3 Oct 2017. 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?
Yes. Results are posted in the registry (first posted 3 Oct 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Percentage of Participants That Experienced a Dose Limiting Toxicity (DLT) (time frame: Up to 26 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 Oct 2017.