Phase I and Consecutive Phase II, Two-arm, Randomized Multi-center Trial in Patients With Advanced Melanoma

NCT01614301 | Unknown Phase 1 DMC

• 1 other identifier: MEL001
• Study Type: interventional
• Target: 136
• Locations: 1 country
• Sites: 1

Brief Summary

A prospective phase I and consecutive phase II, twoarm, randomized multi-center trial of temsirolimus in combination with pioglitazone, etoricoxib and metronomic low-dose trofosfamide versus dacarbazine (DTIC) in patients with advanced melanoma Phase I: To determine the dose of temsirolimus to be used in phase II part of the study Phase II: To determine overall survival Secondary objectives

• To evalulate response rate
• To evaluate time to progression (TTP)
• To evalulate time to partial response (time to PR or better)(TPR)
• To evaluate quality of life
• To evaluate tolerability and safety

Conditions

Advanced Melanoma

Keywords

advanced Melanoma

Outcome Measures

Primary Outcomes (1)

• response rate

  2014

Secondary Outcomes (1)

• Time to progession

  2014

Study Arms (2)

Experimental Arm

EXPERIMENTAL

Temsirolimus: 15 or 25 mg iv weekly , week 1+.In the phase I part of the study the finally used dosis will be determined. Pioglitazone (Actos) 60 mg p.o. daily, day 1+. Etoricoxib (Arcoxia) 60 mg p.o. daily, day 1+ Trofosfamide (Ixoten) 50 mg p.o. thrice daily as metronomic angiostatically and immunomodulatory acting therapy, day 1+. Treatment until disease progression or toxicity

Drug: dacarbazine (DTIC), Trofosfamide, Etoricoxib, Pioglitazone, Temsirolimus

Controll Arm

OTHER

Dacarbazine (DTIC) 1000 mg/m2 day 1, every 3 weeks. The total number of DTIC cycles should not exceed 6 cycles due to cumulative toxicity.

Drug: dacarbazine (DTIC), Trofosfamide, Etoricoxib, Pioglitazone, Temsirolimus

Interventions

dacarbazine (DTIC), Trofosfamide, Etoricoxib, Pioglitazone, Temsirolimus DRUG

Dacarbazine (DTIC) 1000 mg/m2 day 1, every 3 weeks The total number of DTIC cycles should not exceed 6 cycles due to cumulative toxicity. Temsirolimus: 15 or 25 mg iv weekly , week 1+.In the phase I part of the study the finally used dosis will be determined. Pioglitazone (Actos) 60 mg p.o. daily, day 1+. Etoricoxib (Arcoxia) 60 mg p.o. daily, day 1+. Trofosfamide (Ixoten) 50 mg p.o. thrice daily as metronomic angiostatically and immunomodulatory actingtherapy, day 1+. Treatment until disease progression or toxicity

Controll Arm; Experimental Arm

Eligibility Criteria

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

You may qualify if:

• At least 18 years of age
• Must be able to adhere to the study visit schedule and other protocol requirements.
• Must be histologically diagnosed with metastatic melanoma and LDH level \> 0.8 ULN
• Measurable lesions
• Subjects must receive study medication as first-line therapy. Preceeding adjuvant therapies are allowed.
• BRAF V600 mutation analysis
• Sufficient bone marrow function: neutrophils ≥ 2x109/l, hemoglobin ≥10 g/dl, platelets ≥ 100x109/l
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2 (see Post Text Supplement 3).
• Required laboratory results:
• Liver function: Total bilirubin \< 1.5 times of upper limit of local institution (ULN), SGPT, SGOT ≤ 2.5 times of upper limit of local institution
• Renal function: serum creatinine ≤ 1.5 ULN
• PT-INR/PT \<1.5 ULN
• Normal cardiac function
• Patients with prior thrombembolic event with adequate anticoagulation
• Life expectancy at least 3 months

You may not qualify if:

• Documented brain metastases unless the patient has completed successful local therapy for central nervous system metastases and has been off of corticosteroids for at least 4 weeks before enrollment.
• Patients who require vitamin K antagonists except for low dose
• Patients with bladder cancer or bladder cancer in their medical history, patients with risk factors for bladder cancer (such as exposure to aromatic amines or heavy tobacco smokers), or macrohematuria of unknown origin
• Prior history of stroke
• Known hypersensitivity to study drugs or to any of the excipients
• Active infection \> grade 2 NCI-CTC version 4.0
• Known diagnosis of HIV, hepatitis B, or hepatitis C infection.
• Severe, unstable, or uncontrolled medical disease which would confound diagnoses or evaluations required by the protocol, including cardiac insufficiency (NYHA I -IV) uncontrolled diabetes including diabetic ketoacidosis, chronic hepatic or renal disease, active uncontrolled infection and chronic inflammatory intestinal disease, autoimmune diseases, peripheral arterial disease, verified coronary heart disease, cerebrovascular disease, acute peptic ulcer or acute gastro-intestinal bleeding.
• Prior radiation therapy \> 25% of bone marrow
• Regular blood transfusions
• Treatment with other experimental substances within 30 days before study start
• Prior immunotherapy with ipilimumab, vaccination, B-raf inhibitor
• Participation in another clinical trial within 30 days before study start or during the trial
• Unwilling or unable to comply with the protocol
• Pregnant or breastfeeding patients. Women of childbearing potential must have a negative pregnancy test performed 7 days prior start of treatment.

Sponsors & Collaborators

• University of Regensburg: lead
• ClinAssess GmbH: collaborator

Study Sites (1)

University of Regensburg

Regensburg, Bavaria, 93053, Germany

RECRUITING

MeSH Terms

Interventions

Dacarbazine; trofosfamide; Etoricoxib; Pioglitazone; temsirolimus

Intervention Hierarchy (Ancestors)

Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Sulfones; Sulfur Compounds; Pyridines; Thiazolidinediones; Thiazoles

Study Officials

• Albrecht Reichle, Professor

  University of Regensburg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor MD

Study Record Dates

• First Submitted: June 5, 2012
• First Posted: June 7, 2012
• Study Start: May 1, 2012
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2016
• Last Updated: June 7, 2012

Record last verified: 2012-06

Locations

DE (1)