High Dose Interleukin-2 Followed by Intermittent Low Dose Temozolomide in Patients With Melanoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Joseph Drabick, Milton S. Hershey Medical Center
ClinicalTrials.gov Identifier:
NCT01124734
First received: March 4, 2010
Last updated: May 19, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Malignant Melanoma
Drug: Interleukin-2
Drug: Temozolomide
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of High Dose Interleukin-2 Followed by Intermittent Low Dose Temozolomide in Patients With Metastatic Malignant Melanoma

Resource links provided by NLM:


Further study details as provided by Milton S. Hershey Medical Center:

Primary Outcome Measures:
  • Determine clinical response to high dose IL2 followed by low dose temozolomide [ Time Frame: two years ] [ Designated as safety issue: Yes ]
    Accrual of first 12 patients


Secondary Outcome Measures:
  • Determine effects of high dose IL2 followed by low dose temozolomide [ Time Frame: two years ] [ Designated as safety issue: Yes ]
    Determine effects of high dose IL2 followed by low dose temozolomide on lymphocyte subsets, particularly the T-reg cells, on cytokine production and anti-melanoma specific t-cell immune cells, on autoimmune laboratory markers and clinical manifestations of autoimmunity.


Estimated Enrollment: 40
Study Start Date: May 2010
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Course 1 of HD IL-2
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.
Drug: Interleukin-2
up to a maximum of 14 doses at 600,000 IU/kg
Other Name: IL-2
Drug: Temozolomide
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.
Other Names:
  • temodar
  • temodol
Experimental: Course 2
The response determined from Course 1 will determine the patient's next step.
Drug: Interleukin-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.
Other Name: IL-2
Drug: Temozolomide
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.
Other Names:
  • temodar
  • temodol

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01124734

Locations
United States, Pennsylvania
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
Sponsors and Collaborators
Milton S. Hershey Medical Center
Investigators
Principal Investigator: Joseph J Drabick, MD Milton S. Hershey Medical Center
  More Information

No publications provided

Responsible Party: Joseph Drabick, Professor of Medicine, Milton S. Hershey Medical Center
ClinicalTrials.gov Identifier: NCT01124734     History of Changes
Other Study ID Numbers: PSHCI 09-067
Study First Received: March 4, 2010
Last Updated: May 19, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Milton S. Hershey Medical Center:
metastatic melanoma

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Temozolomide
Interleukin-2
Dacarbazine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014