High Dose Interleukin-2 Followed by Intermittent Low Dose Temozolomide in Patients With Melanoma
| Status: | Completed |
|---|---|
| Conditions: | Skin Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 2/14/2019 |
| Start Date: | May 2010 |
| End Date: | July 1, 2018 |
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.
(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.
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.
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.
Inclusion Criteria:
- 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.
- 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
Exclusion Criteria:
- 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
We found this trial at
1
site
500 University Dr
Hershey, Pennsylvania 17033
Hershey, Pennsylvania 17033
(717) 531-6955
Penn State Milton S. Hershey Medical Center Penn State Milton S. Hershey Medical Center, Penn...
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