A Phase 1/2 , Multi-Center, Blinded, Randomized, Controlled Study of the Safety and Efficacy of the Human Monoclonal Antibody to Human av Integrins (CNTO 95), Alone and in Combination with Dacarbazine, in Subjects with Stage IV Melanoma

Phase 1

• Conditions: Malignant Melanoma Stage IV; MedDRA version: 9.1 Level: LLT Classification code 10025671 Term: Malignant melanoma stage IV

• Registration Number: EUCTR2004-002130-18-GB
• Lead Sponsor: Centocor B.V.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2006-05-02
• Study Completion: 2009-02-11
• Last Update Posted: 25 November 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 0

Inclusion Criteria

1. Male or female = 18 years.
2. Provide signed informed consent(s) prior to any study specific-procedures and agree to comply with all protocol-specified procedures.
3. Histologically confirmed melanoma (including ocular and mucosal).
4. Documented AJCC Stage III unresectable or Stage IV melanoma (Phase 1); AJCC Stage IV melanoma (Phase 2).
5. Radiographically measurable disease (at least 1 measurable lesion as defined by RECIST) or measurable skin lesions.
6. Prior therapy:
a. In Phase 1, prior chemotherapy for metastatic melanoma is allowed.
b. In Phase 2, subjects previously untreated for melanoma by chemotherapy will be enrolled. Prior immunotherapy and biotherapy are permitted.
7. ECOG performance status = 2.
8. Life expectancy of = 12 weeks.
9. At least 4 weeks from prior major surgery to date of first study agent administration. Subjects must have recovered or stabilized from prior surgery.
10. Women of childbearing potential must be using adequate birth control measures (eg, oral contraceptives, complete abstinence, intrauterine device, barrier method with spermicide, or surgical sterilization) and not be breast-feeding, and men must be using barrier contraception with spermicide. Subjects must agree to continue such precautions for 6 months after the last administration of study agent. Women of childbearing potential must test negative for pregnancy at screening with a ß-HCG serum pregnancy test.
11. Adequate bone marrow, liver, and renal function:
a. Neutrophils = 1500/mm(3) (or = 1.5 × 10(9)/L).
b. Platelets = 100,000/mm(3) (or = 100 × 10(9)/L).
c. Hemoglobin = 10.0 g/dL (or = 100 g/L).
d. Bilirubin = 1.5 × upper limit of normal (ULN); (= 3.0 × ULN with liver metastases).
e. Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) = 2.5 × ULN (= 5.0 × ULN with liver metastases).
f. Serum creatinine = 1.5 × ULN.
g.Prothrombin time (PT)/international normalized ratio (INR) and activated partial thromboplastin time (aPTT) within normal range.
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

1. Prior chemotherapy for melanoma (Phase 2).
2. Received any investigational drug, systemic cancer therapy, or generalized radiation therapy within 30 days of date of first study agent administration.
3. History of receiving murine or human/murine recombination products of human a? integrins.
4. History of anaphylaxis or severe allergic reaction(s) to mouse proteins or any component of CNTO 95.
5. Clinically important active infection.
6. Known human immunodeficiency virus (HIV) positivity.
7. Presence of nonmeasurable lesions only (ie, bone metastases or malignant effusions).
8. CNS metastases (except for metastases that have been stable for at least 6 months after resection or irradiation).
9. Prior radiation to target lesions (palliative radiation therapy to nontarget lesions is permitted).
10. Concomitant or prior malignancy (other than the one under study) except adequately treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or other cancer for which the subject has been disease-free for = 5 years.
11. Concurrent immunotherapy, biotherapy, radiotherapy, chemotherapy, or investigational therapy.
12. Requires concurrent therapeutic use of anticoagulation (except for low-dose prophylactic warfarin, anti-platelet agents, or low-molecular-weight heparin).
13. History of bleeding diathesis.
14. Recurrent deep vein thrombosis (DVT) or DVT within the 6 months preceding treatment assignment/randomization.
15. Planned surgery (except for minor surgical procedures) during study period.
16. History of uveitis.
17. Any medical condition that, in the opinion of the investigator, may compromise the compliance of the subject to receive study treatment.
18. Requires hematopoietic growth factors or transfusion of blood products to meet eligibility criteria.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Evaluate the safety and efficacy of CNTO 95, alone and in combination with dacarbazine (DTIC), as compared to DTIC alone.;Secondary Objective: To assess the pharmacokinetics and pharmacodynamics of CNTO 95 when used alone or in combination with DTIC. Exploratory pharmacogenomics will be evaluated in consenting subjects.;Primary end point(s): Progression-free survival defined as the time interval from the date of randomization to the date of initial documented disease progression on study or date of death.