Melanoma (Skin)Phase 2NCT00602576
Temozolomide and Sorafenib in Treating Patients With Metastatic or Unresectable Melanoma
A Phase 2 study testing sorafenib tosylate and temozolomide in people with Melanoma (Skin), run by Abramson Cancer Center at Penn Medicine at 1 site in United States.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Melanoma (Skin)
- What is being tested?
- sorafenib tosylate and temozolomide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 169 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jan 2005to 26 Jul 2009
- Phase
- Phase 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 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically or cytologically confirmed melanoma that is metastatic or unresectable.
- The following groups are eligible with regard to prior therapy in either the adjuvant or metastatic disease setting:
- No prior therapy c) Immunotherapy consisting of Interferon, Interleukin-2 or GM-CSF. d) Chemotherapy, either single-agent or combination. Prior temozolomide is allowable e) Vaccine therapy f) Prior sorafenib is allowable
- NB: There is no limit on the number of prior therapies
- Prior radiation therapy is allowed. However, if radiation has been administered to a lesion, there must be radiographic evidence of progression of that lesion in order for that lesion to constitute measurable disease or to be included in the measured target lesions.
- Measurable disease by RECIST criteria. Cutaneous lesions measuring at least 1 cm will be considered. Baseline CT or MRI scans of disease sites must be performed within 4 weeks of study entry. For patients with bone metastases, a baseline bone scan must be performed within 4 weeks of study entry.
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- Age > 18 years.
- Eastern Cooperative Oncology Group performance status of 0 or 1.
- Baseline laboratory values (evaluated within 14 days of randomization):
- White Blood Count > 3,000/mm3 Absolute Granulocyte Count > 1,500/mm3 Platelet Count > 100,000/mm3 Serum creatinine < 2.0 x upper limit of normal (ULN) or serum creatinine clearance estimated by the MDRD formula Total Bilirubin < 1.5 x ULN (< 3.0 x ULN in the presence of Gilbert's disease AST/ALT < 2.5 x ULN (< 5.0 ULN in the presence of liver metastases) INR < 1.5 and a PTT within the upper limit of normal (if on anticoagulation baseline INR before starting anticoagulation must be <1.5)
- Patients must have discontinued active immunotherapy (IL-2, interferon, CTLA-4, etc.) or chemotherapy at least 4 weeks prior to entering the study and recovered from adverse events due to those agents. Patients must not receive any other investigational anticancer therapy during the period on study or the four weeks prior to entry, with the exception of vaccines.
- Patients with brain metastases must have completed radiation therapy if radiation is clinically indicated at the time of diagnosis and discontinued steroids prior to enrollment.
- The effects of sorafenib, temozolomide on the developing human fetus are unknown. For this reason and because antiangiogenic agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant while participating in this study, she should inform her treating physician immediately. If a man impregnates a woman while participatig in this study, he should inform his treating physician immediately as well.
Who cannot join
- Patients must not have other current malignancies, other than basal cell skin cancer, squamous cell skin cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast.
- Patients must not have a serious intercurrent illness including, but not limited to, ongoing or active infection requiring parental antibiotics, clinically significant cardiovascular disease (e.g. uncontrolled hypertension, myocardial infarction, unstable angina), New York heart association grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, or grade II or greater peripheral vascular disease within 1 year prior to study entry, or psychiatric illness/social situations that would limit compliance with study requirements.
- Patients must not be taking cytochrome P450 enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine or phenobarbital), rifampin or St. John's wort.
- Women must not be pregnant or breast-feeding as the agents used in this study may be teratogenic to a fetus and there is no information on the excretion of the agents or their metabolites into breast milk. All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy.
- Because patients with immune deficiency are at increased risk of lethal infections when treated with bone marrow-suppressive therapy, HIV-positive patients are excluded from the study. For patients receiving combination anti-retroviral therapy, the potential impact of pharmacokinetic interactions with sorafenib, temozolomide is unknown. Appropriate studies may be undertaken in patients with HIV and those receiving combination anti-retroviral therapy in the future.
Trial locations and contacts
1 site in 1 country.
United States1 site
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104-4283
About this study
Official title: Randomized Phase II Study Comparing Two Schedules Of Temozolomide In Combination With Bay 43-9006 In Patients With Advanced Melanoma
RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving temozolomide together with sorafenib may kill more tumor cells.
PURPOSE: This randomized phase II trial is studying two different schedules of temozolomide when given together with sorafenib to compare how well they work in treating patients with metastatic or unresectable melanoma.
Read the detailed description
OBJECTIVES:
Primary
- To measure the progression-free survival of patients with metastatic or unresectable melanoma with no brain metastasis or no prior treatment with temozolomide (TMZ) treated with sorafenib tosylate in combination with two different schedules (extended daily dosing vs standard dosing) of TMZ.
- To measure the progression-free survival of patients with or without brain metastasis and prior treatment with TMZ treated with sorafenib in combination with extended daily dosing of TMZ.
- To measure the progression-free survival of patients with brain metastasis and no prior treatment with TMZ treated with sorafenib in combination with standard dosing TMZ.
- To estimate the median time to progression in all patients.
- To quantify the number and percent of patients who have stable disease after 6 months of treatment (failure to progress).
- To choose the optimal combination dosing regimen for further study.
Secondary
- To estimate and define the objective response rate in these patients.
- To characterize the duration of objective responses in these patients.
- To estimate the incidence of new symptomatic brain metastasis in these patients.
- To measure overall survival of these patients.
OUTLINE: This is a multicenter study. Patients are stratified according to prior brain metastases (yes vs no) and prior treatment with temozolomide (TMZ) (yes vs no). Patients with no prior brain metastases who did not receive prior treatment with TMZ are randomized to 1 of 2 treatment arms. These patients are further stratified according to prior treatment with sorafenib tosylate (yes vs no). Patients with or without prior brain metastases who received prior treatment with TMZ are assigned to arm I. Patients with prior brain metastases who did not receive prior treatment with TMZ are assigned to arm II.
- Arm I: Patients receive oral sorafenib tosylate twice daily on days -7 to 56 of course 1 and on days 1-56 of all subsequent courses. Patients also receive oral TMZ once daily on days 1-42.
- Arm II: Patients receive sorafenib tosylate as in arm I and oral TMZ once daily on days 1-5 and 29-33.
In both arms, courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.
- Conditions
- Melanoma (Skin)
- Being tested
- sorafenib tosylate, temozolomide
- Keywords
- recurrent melanoma, stage III melanoma, stage IV melanoma
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sorafenib tosylateDrug
Also called nexavar
Given orally
temozolomideDrug
Also called temodar
Given orally
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | Patients who were temozolomide naive and had no brain metastases received oral sorafenib tosylate twice daily on days -7 to 56 of course 1 and on days 1-56 of all subsequent courses. Patients also receive oral TMZ once daily on days 1-42. Receives: Drug: sorafenib tosylate; Drug: temozolomide |
| Arm B | Experimental | Patients who were temozolomide naive and had no brain metastases received sorafenib tosylate as in arm A and oral TMZ once daily on days 1-5 and 29-33. Receives: Drug: sorafenib tosylate; Drug: temozolomide |
| Arm C | Experimental | Patient with or without treated brain metastases who were treated with prior temozolomide and progressed were treated with oral sorafenib tosylate twice daily on days -7 to 56 of course 1 and on days 1-56 of all subsequent courses. Patients also receive oral TMZ once daily on days 1-42. Receives: Drug: sorafenib tosylate; Drug: temozolomide |
| Arm D | Experimental | Patients with treated brain metastases were treated with sorafenib tosylate as in arm B and oral TMZ once daily on days 1-5 and 29-33. Receives: Drug: sorafenib tosylate; Drug: temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of 6 Month Progression-Free Survival
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Measured: 6 months
Secondary outcomes (2)
Response Rate
Response Rate as defined by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Measured: Approximately 3 years
Overall Survival Rate
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2008 (estimated)
- Study start1 Jan 2005
- Primary completion21 Dec 2008
- Study completion26 Jul 2009
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 Melanoma (Skin)Studies of the same condition, open and under way.
- More trials run by Abramson Cancer Center at Penn MedicineThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 4 arm parallel phase II study Arms A and B are randomized to different schedules of temozolomide Arm C is prior temozolomide-refractory patients Arm D is brain metastases patients
- Masking
- None (open label)
- Enrolment
- 169 participants (actual)
Sponsor and investigators
- Lead sponsor
- Abramson Cancer Center at Penn Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Ravi Amaravadi, MD, Principal investigator, Abramson Cancer Center at Penn Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00602576
- Sponsor's protocol ID
- CDR0000580808
- Other IDs
- 06604, 802514, P30CA016520
- Status last verified
- Jun 2022
- First submitted
- 25 Jan 2008
- Last updated
- 14 Jun 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Phase II Study Comparing Two Schedules Of Temozolomide In Combination With Bay 43-9006 In Patients With Advanced Melanoma
- ClinicalTrials.gov ID
- NCT00602576
- Acronym / sponsor ID
- CDR0000580808
- Conditions
- Melanoma (Skin)
- Keywords
- recurrent melanoma, stage III melanoma, stage IV melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 169 participants (actual)
- Lead sponsor
- Abramson Cancer Center at Penn MedicineUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 1 Jan 2005 (actual)
- Primary completion
- 21 Dec 2008 (actual)
- Study completion
- 26 Jul 2009 (actual)
- First posted
- 28 Jan 2008 (estimated)
- Results
- Posted 14 Jun 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving temozolomide together with sorafenib may kill more tumor cells.
PURPOSE: This randomized phase II trial is studying two different schedules of temozolomide when given together with sorafenib to compare how well they work in treating patients with metastatic or unresectable melanoma.
Detailed description
OBJECTIVES:
Primary
- To measure the progression-free survival of patients with metastatic or unresectable melanoma with no brain metastasis or no prior treatment with temozolomide (TMZ) treated with sorafenib tosylate in combination with two different schedules (extended daily dosing vs standard dosing) of TMZ.
- To measure the progression-free survival of patients with or without brain metastasis and prior treatment with TMZ treated with sorafenib in combination with extended daily dosing of TMZ.
- To measure the progression-free survival of patients with brain metastasis and no prior treatment with TMZ treated with sorafenib in combination with standard dosing TMZ.
- To estimate the median time to progression in all patients.
- To quantify the number and percent of patients who have stable disease after 6 months of treatment (failure to progress).
- To choose the optimal combination dosing regimen for further study.
Secondary
- To estimate and define the objective response rate in these patients.
- To characterize the duration of objective responses in these patients.
- To estimate the incidence of new symptomatic brain metastasis in these patients.
- To measure overall survival of these patients.
OUTLINE: This is a multicenter study. Patients are stratified according to prior brain metastases (yes vs no) and prior treatment with temozolomide (TMZ) (yes vs no). Patients with no prior brain metastases who did not receive prior treatment with TMZ are randomized to 1 of 2 treatment arms. These patients are further stratified according to prior treatment with sorafenib tosylate (yes vs no). Patients with or without prior brain metastases who received prior treatment with TMZ are assigned to arm I. Patients with prior brain metastases who did not receive prior treatment with TMZ are assigned to arm II.
- Arm I: Patients receive oral sorafenib tosylate twice daily on days -7 to 56 of course 1 and on days 1-56 of all subsequent courses. Patients also receive oral TMZ once daily on days 1-42.
- Arm II: Patients receive sorafenib tosylate as in arm I and oral TMZ once daily on days 1-5 and 29-33.
In both arms, courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- 4 arm parallel phase II study Arms A and B are randomized to different schedules of temozolomide Arm C is prior temozolomide-refractory patients Arm D is brain metastases patients
| Arm | Type | Receives |
|---|---|---|
| Arm A | Experimental | Drug: sorafenib tosylate, Drug: temozolomidePatients who were temozolomide naive and had no brain metastases received oral sorafenib tosylate twice daily on days -7 to 56 of course 1 and on days 1-56 of all subsequent courses. Patients also receive oral TMZ once daily on days 1-42. |
| Arm B | Experimental | Drug: sorafenib tosylate, Drug: temozolomidePatients who were temozolomide naive and had no brain metastases received sorafenib tosylate as in arm A and oral TMZ once daily on days 1-5 and 29-33. |
| Arm C | Experimental | Drug: sorafenib tosylate, Drug: temozolomidePatient with or without treated brain metastases who were treated with prior temozolomide and progressed were treated with oral sorafenib tosylate twice daily on days -7 to 56 of course 1 and on days 1-56 of all subsequent courses. Patients also receive oral TMZ once daily on days 1-42. |
| Arm D | Experimental | Drug: sorafenib tosylate, Drug: temozolomidePatients with treated brain metastases were treated with sorafenib tosylate as in arm B and oral TMZ once daily on days 1-5 and 29-33. |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Histologically or cytologically confirmed melanoma that is metastatic or unresectable.
- The following groups are eligible with regard to prior therapy in either the adjuvant or metastatic disease setting:
- NB: There is no limit on the number of prior therapies
- Prior radiation therapy is allowed. However, if radiation has been administered to a lesion, there must be radiographic evidence of progression of that lesion in order for that lesion to constitute measurable disease or to be included in the measured target lesions.
- Measurable disease by RECIST criteria. Cutaneous lesions measuring at least 1 cm will be considered. Baseline CT or MRI scans of disease sites must be performed within 4 weeks of study entry. For patients with bone metastases, a baseline bone scan must be performed within 4 weeks of study entry.
Key exclusion criteria (5 listed)
- Patients must not have other current malignancies, other than basal cell skin cancer, squamous cell skin cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast.
- Patients must not have a serious intercurrent illness including, but not limited to, ongoing or active infection requiring parental antibiotics, clinically significant cardiovascular disease (e.g. uncontrolled hypertension, myocardial infarction, unstable angina), New York heart association grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, or grade II or greater peripheral vascular disease within 1 year prior to study entry, or psychiatric illness/social situations that would limit compliance with study requirements.
- Patients must not be taking cytochrome P450 enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine or phenobarbital), rifampin or St. John's wort.
- Women must not be pregnant or breast-feeding as the agents used in this study may be teratogenic to a fetus and there is no information on the excretion of the agents or their metabolites into breast milk. All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy.
- Because patients with immune deficiency are at increased risk of lethal infections when treated with bone marrow-suppressive therapy, HIV-positive patients are excluded from the study. For patients receiving combination anti-retroviral therapy, the potential impact of pharmacokinetic interactions with sorafenib, temozolomide is unknown. Appropriate studies may be undertaken in patients with HIV and those receiving combination anti-retroviral therapy in the future.
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 |
|---|---|---|
| sorafenib tosylateAlso: nexavarGiven orally | Drug | Arm A, Arm B, Arm C, Arm D |
| temozolomideAlso: temodarGiven orally | Drug | Arm A, Arm B, Arm C, Arm D |
Primary outcome
Rate of 6 Month Progression-Free Survival
Time frame: 6 months
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
2 secondary outcomes
Response Rate
Time frame: Approximately 3 years
Overall Survival Rate
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Ravi Amaravadi, MD principal investigator
Abramson Cancer Center at Penn Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing sorafenib tosylate and temozolomide in people with Melanoma (Skin), run by Abramson Cancer Center at Penn Medicine 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 13 inclusion and 5 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 14 Jun 2022. 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 phase mean?
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 14 Jun 2022). 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?
Rate of 6 Month Progression-Free Survival (time frame: 6 months). 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 14 Jun 2022.