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

• Register: EUCTR
• Last refreshed on: 21 July 2021
• Main ID: EUCTR2011-002611-29-DE
• Date of registration: 08/09/2011
• Prospective Registration: Yes
• Primary sponsor: Freistaat Bayern
• Public title: 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
• Scientific title: 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
• Date of first enrolment: 04/04/2012
• Target sample size: 48
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-002611-29
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Germany

Contacts

• Name: Study office
• Affiliation: University clinic Regensburg

• Name: Study office
• Affiliation: University clinic Regensburg

Key inclusion & exclusion criteria

Inclusion criteria:
• 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 or metastatic uveal carcinoma and LDH level > 0.8 ULN
• Measurable lesions (also cutaneous lesions)
• Subjects may receive study medication as >= second-line therapy following immune therapy or failure of BRAF- and/or MEK targeting therapy independently of the BRAF mutation Status
• 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:
a) 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
b) Renal function: serum creatinine = 1.5 ULN
c)PT-INR/PT <1.5 ULN
• Normal cardiac function
• Also patients with prior thromboembolic event and adequate anticoagulation are permitted for enrollment
• Life expectancy at least 3 months
• Written informed consent of the patient prior to screening procedures
• Adequate contraception in women capable of bearing children and men with partner capable of bearing children (combined oral contraceptives, hormone-releasing intrauterine contraceptive device, hormonal contraceptive implants, hormonal contraceptive injectables, surgical sterilization)
• Any previous surgery must have taken place more than 4 weeks prior to inclusion
• Previous radiation therapy must have involved less than 25% of bone marrow, and must have been completed more than 4 weeks prior to inclusion.
• For patients with controlled diabetes mellitus glucose levels have to be monitored continuously and the treating diabetologist has to be informed about the study participation of the patient.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
• 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 vaccination
• 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.
• Patients with seizure disorders requiring medication (such as steroids or antiepileptics)
• Patients with evidence or history of bleeding diathesis
• Major surgery within 4 weeks prior to start of study or incomplete wound healing
• Drug or alcohol abuse
• Psychological or social conditions that may interfere with the patients participation in the study or evaluation of the study results.
• Known (at time of entry) gastrointestinal disorder, including malabsorbtion or active gastric ulcer, present to the extent that it might interfere with oral intake and absorption of study medication
• Patients undergoing dialysis or creatinine clearance <30 mL per minute, defined according to MDRD
• Patients with medically uncontrolled hypertension (RR continuously > 140/90 mm Hg
• Any previous or concurrent malignancy or any cancer unless curatively treated > 3 years prior to study entry except cervical carcinoma in situ or adequate basal cell carcinoma
• Any urothelial cell carcinoma in the medical history
• Patients who have experienced bronchospasm, acute rhinitis, nasal polyps, angioneurotic oedema, urticaria, or allergic type reactions after acetyl-salicylic acid or NSAIDs including COX-2 (cyclooxygenase-2) inhibitors


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

metastatic melanoma or metastatic uveal carcinoma

Intervention(s)

Trade Name: Torisel
Product Name: Temsirolimus
Product Code: CCI-779
Pharmaceutical Form: Concentrate and solvent for solution for infusion
INN or Proposed INN: TEMSIROLIMUS
CAS Number: 162635-04-3
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 30-

Trade Name: Actos
Product Name: Pioglitazone
Pharmaceutical Form: Tablet
INN or Proposed INN: PIOGLITAZONE
CAS Number: 111025-46-8
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 30-

Trade Name: Arcoxia
Product Name: Etoricoxib
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ETORICOXIB
CAS Number: 202409-33-4
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 30-

Trade Name: Arcoxia
Product Name: Etoricoxib
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ETORICOXIB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 60-

Trade Name: Ixoten
Product Name: Trofosfamide
Pharmaceutical Form: Coated tablet
INN or Proposed INN: TROFOSFAMIDE
CAS Number: 22089-22-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Trade Name: Actos
Product Name: Pioglitazone
Pharmaceutical Form: Tablet
INN or Proposed INN: PIOGLITAZONE
CAS Number: 111025-46-8
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-

Product Name: Dacarbazine
Pharmaceutical Form: Powder and solvent for solution for injection/infusion
INN or Proposed INN: DACARBAZINE
CAS Number: 4342-03-4
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 100-1000

Primary Outcome(s)

Primary end point(s): Phase I:
occurrence of DLTs in the first 3 weeks of treatment

Phase II:
ORR

Main Objective: Phase I:
To determine the dose of temsirolimus to be used in phase II part of the study
Phase II:
To determine overall survival

Timepoint(s) of evaluation of this end point: Phase I:
after 3 weeks of treatment

Phase II:
every 2nd cycle, end of treatment and follow up (if no progression occured before)

Secondary Objective: • 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

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: • Overall survival: every 3 month in follow up within assessment
• time to progression (TTP): every 2nd cycle, end of treatment and follow up (if no progression occured before)
• time to partial response (time to PR or better) (TPR): every 2nd cycle and ent of treatment and follow up (if no progression occured before)
• quality of life: at baseline, start of every cycle and ent of treatment.
• tolerability and safety: every cycle, end of treament and follow up

Secondary end point(s): • Overall survival
• time to progression (TTP)
• time to partial response (time to PR or better)
(TPR)
• quality of life
• tolerability and safety

Secondary ID(s)

MEL001

Ethics review

Status: Approved
Approval date: 04/04/2012
Contact: