Malignant MelanomaPhase 2NCT01124734
High Dose Interleukin-2 Followed by Intermittent Low Dose Temozolomide in Patients With Melanoma
A Phase 2 study testing Interleukin-2 and Temozolomide in people with Malignant Melanoma, run by Milton S. Hershey Medical Center at 1 site in United States.
Trial summary
The investigators have observed that many patients who had received high dose Interleukin-2 (IL2) and failed to respond to it but who then go immediately to temozolomide seemed to enjoy extremely good responses which seem better quality and longer duration than typically observed for temozolomide alone. 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?
- Interleukin-2 and Temozolomide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- May 2010to 1 Jul 2018
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Pathologically confirmed metastatic malignant melanoma
- Age > 18 years
- Eastern Cooperative Oncology Group performance status of 0 or 1
- Patients considered good candidate for conventional high dose IL-2
- No chemotherapy, hormonal therapy, immunotherapy or radiation therapy within 1 month of entry
- Patients with a history or clinical evidence of brain metastasis must have completed radiation therapy or surgical treatment of brain lesions and have no evidence of central nervous system progression for at least 8 weeks at the time of enrollment.
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- Patients may have had prior high dose IL-2 or temozolomide but not together or with high dose IL-2 followed by temozolomide
- Patients may have had prior high dose interferon as adjuvant treatment for high risk melanoma
- Serum creatinine < 2 mg/dL
- Bilirubin < 2 mg/dL
Who cannot join
- Inability to provide informed consent
- Hypersensitivity to temozolomide or HD IL-2
- Active gastrointestinal disorder or cardiac disorders
- Ejection fraction < 50% by echocardiogram or corrected diffusing capacity of lung for carbon monoxide < 50% on diffusion capacity testing pulmonary function tests
- platelets < 100 K, neutrophils < 1000
- Serum Creatinine < 2 x the upper limits of normal
- Chronic use of steroids other than for simple adrenal replacement
Trial locations and contacts
1 site in 1 country.
United States1 site
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033
About this study
Official title: Phase II Trial of High Dose Interleukin-2 Followed by Intermittent Low Dose Temozolomide in Patients With Metastatic Malignant Melanoma
The investigators have observed that many patients who had received high dose Interleukin-2 (IL2) and failed to respond to it but who then go immediately to temozolomide seemed to enjoy extremely good responses which seem better quality and longer duration than typically observed for temozolomide alone. To date, the investigators have observed 5 sequentially treated patients with metastatic melanoma who had failed high dose IL-2 but who then went on to receive immediate temozolomide. Two of these patients had complete responses and 3 had very strong partial response. In a recent phase II study of extended low dose temozolomide alone given in the same manner as the post IL-2 patients noted above, the response rate was 12.5% and all of these were partial responses only. The responses that the investigators observed were at a much higher rate of response as well as much better quality than expected for temozolomide. The responses were also better than those observed when temozolomide was given first and then followed by high dose IL-2. The investigators concluded that perhaps the major benefit the investigators observed was a result of the prior high dose IL-2 therapy modulated by the temozolomide and that the sequence of treatment was clearly crucial for this response.
Read the detailed description
Metastatic malignant melanoma remains a disease with a very poor prognosis and median survival duration of less than one year. Durable remissions with conventional therapy are rare and therefore clinical trials remain a primary treatment modality for metastatic disease. There are 2 currently FDA-approved therapies for metastatic melanoma. Chemotherapy with single agent parenteral dacarbazine or its oral pro-drug, temozolomide, are capable of producing responses in 6.5 to 20% of patients. These responses are usually minor to partial at best and are not durable. Combination with other chemotherapeutic drugs has not been successful. The immune system also seems to play a role in malignant melanoma. High dose Interferon therapy is the current standard therapy for the adjuvant treatment of stage IIB, IIC and III melanoma after surgical resection in which it has shown to result in modest improvements in disease free survival and overall survival. In metastatic disease, various immunologic approaches have been employed as well. High dose IL-2 can produce a response rate of about 10-15% in patients with metastatic melanoma. About 5-10% of responses are complete and some of these complete responses are durable so that the lucky few patients who have a durable complete response are for all intents and purposes cured. Attempts to combine chemotherapy with immunotherapy, although improving response rates, has not impacted survival as summarized in recent meta-analysis.
- Conditions
- Malignant Melanoma
- Being tested
- Interleukin-2, Temozolomide
- Keywords
- Metastatic melanoma
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Interleukin-2Drug
Also called IL-2
Participants will receive IL-2 up to a maximum of 14 doses at 600,000 IU/kg
TemozolomideDrug
Also called Temodar, Temodal, Temcad, Temodal
Participants receive temozolomide at 75 mg/m2 after completion of the second cycle of high dose IL-2. Participants take the medication at bedtime daily. Four weeks after Cycle 2 of a course, they would take it for 21 days.
| Study group | Role | What they receive |
|---|---|---|
| Course 1 Cycle 1 and Cycle 2 | Experimental | Course 1 Cycle 1: Participants will be given high-dose Interleukin-2 (HD IL-2) 600,000 IU/kg, up to 14 doses at 8 hour intervals.
Course 1 Cycle 2: Participants will be given high-dose Interleukin-2 (HD IL-2) 600,000 IU/kg, up to 14 doses at 8 hour intervals. On the day after discharge, patients will be given oral temozolomide at 75 mg/m2 daily for 21 days. Receives: Drug: Interleukin-2; Drug: Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Response to High-Dose Interleukin-2 (H-D IL-2) Followed by Low Dose Temozolomide
Clinical response was measured using the Response Evaluation Criteria In Solid Tumors (RECIST) criteria categorizing responses as complete response (CR), partial response (PR), minor response (MR), stable disease (SD), or progressive disease (PD).
Measured: 2 years
Duration of Response to High-Dose Interleukin-2 (H-D IL-2) Followed by Low Dose Temozolomide
Duration of response is defined as the length (measured in days) from the date of best response to the date of progression (if any), or to the date of last follow-up (if no progression is observed). The duration of response is applicable for those CR/MR/PR/SD subjects only.
Measured: 8 years
Safety and Toxicity of H-D IL-2 Followed by Low Dose Temozolomide
Safety and toxicity in this study population was evaluated using the NCI Common Toxicity Criteria. The unit of measure is the number of study participants with one or more unexpected and related (even remotely) SAE.
Measured: 2 years
Secondary outcomes (1)
Effect of High Dose IL2 Followed by Low Dose Temozolomide on Lymphocyte Subsets (Autoimmune Biomarkers)
The effect outcome is measured by the change in percentage of circulating lymphocyte cells (autoimmune biomarkers) that express the noted phenotype. This percentage change is determined by comparing the values obtained within 7 days of participant going off treatment against the baseline values.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2010 (estimated)
- Study startMay 2010
- Primary completion18 Jul 2017
- Study completion1 Jul 2018
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.
- More trials run by Milton S. Hershey Medical CenterThe 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
- Not applicable
- Intervention model
- Single group
- Model description
- Single group, open label study
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Milton S. Hershey Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Joseph Drabick, Milton S. Hershey Medical Center
- Investigators
- Joseph J Drabick, MD, Principal investigator, Milton S. Hershey Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01124734
- Sponsor's protocol ID
- PSHCI 09-067
- Status last verified
- Jan 2019
- First submitted
- 4 Mar 2010
- Last updated
- 12 Feb 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of High Dose Interleukin-2 Followed by Intermittent Low Dose Temozolomide in Patients With Metastatic Malignant Melanoma
- ClinicalTrials.gov ID
- NCT01124734
- Acronym / sponsor ID
- PSHCI 09-067
- Conditions
- Malignant Melanoma
- Keywords
- Metastatic melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Milton S. Hershey Medical CenterUniversity, hospital or other
- Study start
- May 2010
- Primary completion
- 18 Jul 2017 (actual)
- Study completion
- 1 Jul 2018 (actual)
- First posted
- 17 May 2010 (estimated)
- Results
- Posted 12 Feb 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators have observed that many patients who had received high dose Interleukin-2 (IL2) and failed to respond to it but who then go immediately to temozolomide seemed to enjoy extremely good responses which seem better quality and longer duration than typically observed for temozolomide alone. To date, the investigators have observed 5 sequentially treated patients with metastatic melanoma who had failed high dose IL-2 but who then went on to receive immediate temozolomide. Two of these patients had complete responses and 3 had very strong partial response. In a recent phase II study of extended low dose temozolomide alone given in the same manner as the post IL-2 patients noted above, the response rate was 12.5% and all of these were partial responses only. The responses that the investigators observed were at a much higher rate of response as well as much better quality than expected for temozolomide. The responses were also better than those observed when temozolomide was given first and then followed by high dose IL-2. The investigators concluded that perhaps the major benefit the investigators observed was a result of the prior high dose IL-2 therapy modulated by the temozolomide and that the sequence of treatment was clearly crucial for this response.
Detailed description
Metastatic malignant melanoma remains a disease with a very poor prognosis and median survival duration of less than one year. Durable remissions with conventional therapy are rare and therefore clinical trials remain a primary treatment modality for metastatic disease. There are 2 currently FDA-approved therapies for metastatic melanoma. Chemotherapy with single agent parenteral dacarbazine or its oral pro-drug, temozolomide, are capable of producing responses in 6.5 to 20% of patients. These responses are usually minor to partial at best and are not durable. Combination with other chemotherapeutic drugs has not been successful. The immune system also seems to play a role in malignant melanoma. High dose Interferon therapy is the current standard therapy for the adjuvant treatment of stage IIB, IIC and III melanoma after surgical resection in which it has shown to result in modest improvements in disease free survival and overall survival. In metastatic disease, various immunologic approaches have been employed as well. High dose IL-2 can produce a response rate of about 10-15% in patients with metastatic melanoma. About 5-10% of responses are complete and some of these complete responses are durable so that the lucky few patients who have a durable complete response are for all intents and purposes cured. Attempts to combine chemotherapy with immunotherapy, although improving response rates, has not impacted survival as summarized in recent meta-analysis.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single group, open label study
| Arm | Type | Receives |
|---|---|---|
| Course 1 Cycle 1 and Cycle 2 | Experimental | Drug: Interleukin-2, Drug: TemozolomideCourse 1 Cycle 1: Participants will be given high-dose Interleukin-2 (HD IL-2) 600,000 IU/kg, up to 14 doses at 8 hour intervals. Course 1 Cycle 2: Participants will be given high-dose Interleukin-2 (HD IL-2) 600,000 IU/kg, up to 14 doses at 8 hour intervals. On the day after discharge, patients will be given oral temozolomide at 75 mg/m2 daily for 21 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Pathologically confirmed metastatic malignant melanoma
- Age > 18 years
- Eastern Cooperative Oncology Group performance status of 0 or 1
- Patients considered good candidate for conventional high dose IL-2
- No chemotherapy, hormonal therapy, immunotherapy or radiation therapy within 1 month of entry
Key exclusion criteria (7 listed)
- Inability to provide informed consent
- Hypersensitivity to temozolomide or HD IL-2
- Active gastrointestinal disorder or cardiac disorders
- Ejection fraction < 50% by echocardiogram or corrected diffusing capacity of lung for carbon monoxide < 50% on diffusion capacity testing pulmonary function tests
- platelets < 100 K, neutrophils < 1000
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 |
|---|---|---|
| Interleukin-2Also: IL-2Participants will receive IL-2 up to a maximum of 14 doses at 600,000 IU/kg | Drug | Course 1 Cycle 1 and Cycle 2 |
| TemozolomideAlso: Temodar, Temodal, Temcad, TemodalParticipants receive temozolomide at 75 mg/m2 after completion of the second cycle of high dose IL-2. Participants take the medication at bedtime daily. Four weeks after Cycle 2 of a course, they would take it for 21 days. | Drug | Course 1 Cycle 1 and Cycle 2 |
Primary outcome
Clinical Response to High-Dose Interleukin-2 (H-D IL-2) Followed by Low Dose Temozolomide
Time frame: 2 years
Clinical response was measured using the Response Evaluation Criteria In Solid Tumors (RECIST) criteria categorizing responses as complete response (CR), partial response (PR), minor response (MR), stable disease (SD), or progressive disease (PD).
Duration of Response to High-Dose Interleukin-2 (H-D IL-2) Followed by Low Dose Temozolomide
Time frame: 8 years
Duration of response is defined as the length (measured in days) from the date of best response to the date of progression (if any), or to the date of last follow-up (if no progression is observed). The duration of response is applicable for those CR/MR/PR/SD subjects only.
Safety and Toxicity of H-D IL-2 Followed by Low Dose Temozolomide
Time frame: 2 years
Safety and toxicity in this study population was evaluated using the NCI Common Toxicity Criteria. The unit of measure is the number of study participants with one or more unexpected and related (even remotely) SAE.
1 secondary outcome
Effect of High Dose IL2 Followed by Low Dose Temozolomide on Lymphocyte Subsets (Autoimmune Biomarkers)
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Joseph J Drabick, MD principal investigator
Milton S. Hershey Medical Center
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 Interleukin-2 and Temozolomide in people with Malignant Melanoma, run by Milton S. Hershey Medical Center 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 10 inclusion and 7 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 12 Feb 2019. 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 12 Feb 2019). 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?
Clinical Response to High-Dose Interleukin-2 (H-D IL-2) Followed by Low Dose Temozolomide (time frame: 2 years). 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 12 Feb 2019.