Overview

This trial is active, not recruiting.

Condition malignant melanoma
Treatments interleukin-2, temozolomide
Phase phase 2
Sponsor Milton S. Hershey Medical Center
Start date May 2010
End date August 2017
Trial size 40 participants
Trial identifier NCT01124734, PSHCI 09-067

Summary

The investigators have recently 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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Patients will be given cycle 1 HD IL-2 600,000 IU/kg. On the day after discharge, patients will be given oral temozolomide at 75 mg/m2 daily for 7 days. Cycle 2 - patients will HD IL-2 600,000 IU/kg. Patient will receive temozolomide at 75 mg/m2 for 21 days after discharge.
interleukin-2 IL-2
up to a maximum of 14 doses at 600,000 IU/kg
temozolomide temodar
Patients would receive temozolomide at 75 mg/m2 beginning 28 days after discharge from receipt of the second cycle of high dose IL-2. Patients would take the medication at bedtime daily. Four weeks after cycle 2 of a course, they would take it for 21 days.
(Experimental)
The response determined from Course 1 will determine the patient's next step.
interleukin-2 IL-2
If complete response, patient would have one course of treatment. If patient has stable, disease, partial response or minor response, patient would have 2 courses courses.
temozolomide temodar
Patients would receive temozolomide at 75 mg/m2 beginning 28 days after discharge from receipt of the second cycle of high dose IL-2. Patients would take the medication at bedtime daily. Four weeks after cycle 2 of a course, they would take it for 21 days.

Primary Outcomes

Measure
Determine clinical response to high dose IL2 followed by low dose temozolomide
time frame: two years

Secondary Outcomes

Measure
Determine effects of high dose IL2 followed by low dose temozolomide
time frame: two years

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Pathologically confirmed metastatic malignant melanoma - Age > 18 years - ECOG 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 mets must have completed radiation therapy or surgical treatment of brain lesions and have no evidence of CNS 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 - EF < 50% by echo or corrected DLCO < 50% on diffusion capacity testing PFTs - PLT < 100K, ANC < 1000 - Serum Cr < 2 x ULN - Chronic use of steroids other than for simple adrenal replacement

Additional Information

Official title Phase II Trial of High Dose Interleukin-2 Followed by Intermittent Low Dose Temozolomide in Patients With Metastatic Malignant Melanoma
Principal investigator Joseph J Drabick, MD
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.
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by Milton S. Hershey Medical Center.