NAM-Trial: Multiferon in Malignant Melanoma

Neoadjuvant Treatment of Locoregional Metastases in Malignant Melanoma (AJCC Stage IIIB/C) With Multiferon: a Phase IIa DeCOG Trial

The current clinical trial shall clarify the efficacy, safety and biologic effects of neoadjuvant treatment with natural interferon-α (Multiferon) in patients with locoregional metastases of melanoma in stage IIIB/C.

Study Overview

• Status: Completed
• Conditions: Locoregional Metastases in Malignant Melanoma Stages IIIB/C
• Intervention / Treatment: Drug: human interferon-α

Detailed Description

The study is an open label, multicenter phase IIa clinical trial which is designed as a pilot project in order to establish the efficacy and tolerability of Multiferon as a neoadjuvant treatment of locoregional metastases. Patients will be treated subsequently in cohorts characterized by different doses (3 - 9 - 18 MIU) to analyze dosage dependent effects.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Tübingen, Germany, 72076
    • Universitätshautklinik Tübingen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Histologically proven cutaneous melanoma
2. Clinical stage IIIB or IIIC (AJCC 2010)
3. ≥ 18 years of age
4. Presence of at least two metastases, not more than 10 metastases, and completely resectable
5. Measurable disease (at least one lesion that can be accurately measured in two perpendicular diameters, with both dimensions at least 10 mm x 10 mm for spiral CT and 5 mm x 5 mm for locoregional metastases assessed by ultrasound or digital photography)
6. ECOG performance status of 0/1
7. Patients with previous adjuvant recombinant interferon-α treatment of any dose are eligible if (i) treatment was stopped at least 1 month before start of treatment and (ii) no progression occurred during interferon-α treatment.

8. No childbearing potential or negative pregnancy test within 14 days before inclusion in women with child bearing potential Women with childbearing potential must be using an effective method of contraception (Pearl-Index < 1, e.g. oral contraceptives, other hormonal contraceptives [vaginal products, skin patches, or implanted or injectable products], or mechanical products such as an intrauterine device or barrier methods [diaphragm, spermicides]) throughout the study and for up to 3 months after the last dose of investigational product, in such a manner that the risk of pregnancy is minimized.

   No men of fathering potential or men of fathering potential must be using an effective method of contraception to avoid conception throughout the study and for up to 3 months after the last dose of investigational product, in such a manner that the risk of pregnancy is minimized.

9. Signed and dated informed consent informed consent before the start of specific protocol procedures

Exclusion Criteria:

1. Mucous membrane or ocular melanoma
2. Any evidence of distant metastasis (e.g. whole body CT-scan including brain scan within 4 weeks before inclusion)
3. Patients with severe cardiac disease (e.g. NYHA Functional Class III or IV, myocardial infarction within 6 months before inclusion, ventricular tachyarrhythmia requiring ongoing treatment, unstable angina pectoris).
4. ALAT or ASAT > 2 x ULN
5. Total bilirubin > 2 x ULN
6. Creatinine > 2 x ULN
7. Evidence or history of depression. If this condition can not be ruled out, the patient should be transferred to a psychiatrist for consultation and further assessment before inclusion.
8. Patients with seizure disorders requiring anticonvulsant therapy

9. Any of the following abnormal baseline hematologic/laboratory values:

   Hb < 10g/dl WBC < 3.0x109 /l Platelets < 100x109 /l

10. Presence of active autoimmune disease
11. Concurrent systemic glucocorticoids or any other systemic immunosuppressive therapy
12. Unwilling or unable to comply with the requirements of the protocol
13. Known infection with HBV, HCV, HIV
14. Pregnant or lactating women
15. Unwillingness or inability to employ an effective barrier method of birth control throughout the study and for up to 3 months after end of treatment in female or male patients
16. Known or suspected allergy to human interferon alpha or any ingredient of the IMP.
17. Any thyroid dysfunctions not responsive to therapy
18. Presence of chronic hepatitis with decompensated liver cirrhosis
19. Immunosuppression in patients with transplantation
20. Evidence or history of bleeding diathesis or coagulopathy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental arm	Drug: human interferon-α; Neoadjuvant treatment: Multiferon is given as flat dosages (3 - 9 - 18 MIU) 5 days per week, subcutaneously for 4 weeks; Other Names: Multiferon

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate	Overall response rate (clinical and radiological) after 4 weeks of treatment (CR + PR) according to immune-related response criteria (irRC)	after 4 weeks of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease control rate	Disease control rate (CR + PR +SD) according to irRC	after 4 weeks of treatment
Rate of histopathological complete responses	Rate of histopathological complete responses	after 4 weeks of treatment
Tolerability	Assessment of numbers of adverse events	after 4 weeks of treatment
Differences in gene expression in metastatic tissue before/after treatment		after 4 weeks of treatment
Dose dependency of effects		after 4 weeks of treatment
Changes of serum markers and PBMC subsets before/after treatment (optional translational side studies)		after 4 weeks of treatment

Collaborators and Investigators

• Sponsor: University Hospital Tuebingen

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: April 19, 2011
• First Submitted That Met QC Criteria: April 21, 2011
• First Posted (Estimate): April 25, 2011

Study Record Updates

• Last Update Posted (Estimate): November 13, 2014
• Last Update Submitted That Met QC Criteria: November 11, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: Malignatn Melanoma
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neoplastic Processes; Neuroendocrine Tumors; Nevi and Melanomas; Neoplasm Metastasis; Melanoma; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Interferons
• Other Study ID Numbers: 5021000