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

NCT01124734 | Completed Phase 2 Results DMC

• 1 other identifier: PSHCI 09-067
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Malignant Melanoma

Keywords

Metastatic melanoma

Outcome Measures

Primary Outcomes (3)

• 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).

  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.

  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.

  2 years

Secondary Outcomes (1)

• Effect of High Dose IL2 Followed by Low Dose Temozolomide on Lymphocyte Subsets (Autoimmune Biomarkers)

  2 years

Study Arms (1)

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.

Drug: Interleukin-2; Drug: Temozolomide

Interventions

Interleukin-2 DRUG

Participants will receive IL-2 up to a maximum of 14 doses at 600,000 IU/kg

Also known as: IL-2

Course 1 Cycle 1 and Cycle 2

Temozolomide DRUG

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.

Also known as: Temodar, Temodal, Temcad, Temodal

Course 1 Cycle 1 and Cycle 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Milton S. Hershey Medical Center: lead

Study Sites (1)

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

Interleukin-2; Temozolomide

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Joseph Drabick, MD
• Organization: Penn State Cancer Institute

jdrabick@pennstatehealth.psu.edu

717 531 5059

Study Officials

• Joseph J Drabick, MD

  Milton S. Hershey Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Model Details: Single group, open label study

Study Record Dates

• First Submitted: March 4, 2010
• First Posted: May 17, 2010
• Study Start: May 1, 2010
• Primary Completion: July 18, 2017
• Study Completion: July 1, 2018
• Last Updated: February 12, 2019
• Results First Posted: February 12, 2019

Record last verified: 2019-01

Locations

US (1)