CLINICAL STUDY ON THE COMBINATION OF RADIATION THERAPY AND IPILIMUMAB, FOR THE TREATMENT OF PATIENTS WITH MELANOMA AND BRAIN METASTASES.
- Conditions
- Patients with melanoma and brain metastasesTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2013-001132-22-ES
- Lead Sponsor
- Grupo Español Multidisciplinar de Melanoma
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 66
1) Willing and able to give written informed consent.
2) Histologic diagnosis of melanoma.
3) First episode of radiological evidence of brain metastases
4) Age>18 years.
5) RTOG-RPA class 2 (Appendix 1)
6) Karnofsky performance status (PS) > 70%.(Appendix 2)
7) Barthel Index of Activities of Daily Living > 10 (Appendix 3)
8) Measurable disease (mWHO criteria).
9) Adequate organ function as determine by the following criteria:
a. WBC >/= 2000/uL
b. Absolute neutrophil count (ANC) >1.5 x 109/L.
c. Platelet count >75 x 109/L.
d. Hemoglobin >9 g/dL. If the patient received a RBC transfusion, the required value of hemoglobin should be met at least 1 week after the most recent transfusion.
e. Serum creatinine f. Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) g. Total bilirubin h. Albumin > 2.5 g/dL
10) Persons of reproductive potential must agree to use an adequate method of contraception throughout treatment and for at least 26 weeks after ipilimumab is stopped:
a. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not post-menopausal. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours before the start of ipilimumab. If the pregnancy test is positive, the patient must not receive ipilimumab and must not be enrolled in the study. Before study enrollment, women of childbearing potential (WOCBP) must be advised of the importance of avoiding pregnancy during study participation and the potential risk factors for an unintentional pregnancy. WOCBP must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 26 weeks after the last dose of investigational product, in such a manner that the risk of pregnancy is minimized. In general, the decision for appropriate methods to prevent pregnancy should be determined by discussions between the investigator and the study subject.
Post-menopause is defined as:
i. Amenorrhea >/=12 consecutive months without another cause, or
ii. For women with irregular menstrual periods and taking hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level >/= 35 mIU/mL.
Women who are using 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, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (eg, vasectomy) should be considered to be of childbearing potential.
b. Men of fathering potential must be using an adequate method of contraception to avoid conception throughout the study, and for up to 26 weeks after the last dose of investigational product in such a manner that the risk of pregnancy is minimized.
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 66
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 66
1) Patients with melanoma and brain metastases with any of the following disease-specific characteristics:
a.Documented evidence of prior progression of melanoma to an ipilimumab-containing regimen (i.e. received at least 2 doses of ipilimumab for either advanced disease or in the adjuvant setting and the disease progressed/relapsed -according to mWHO criteria- within 24 weeks since the first dose of ipilimumab)
b.Prior radiation therapy to the brain
c.Other prior antineoplastic therapies for brain metastases.
d.Patients with cerebral metastases as the only location of the disease, for which local therapy (neurosurgery, radiosurgery) could achieve a disease-free status
e.Patients with a rapid clinical deterioration, or with risk of herniation, or who require unstable ascending dosing of supportive medication in the last week -including anti-convulsivants, steroids and analgesics-, or who require dexamethasone > 16 mg/d (or other glucocorticoid at an equipotent dose), or with a high LDH (> 2 x ULN).
2)Any other malignancy form which the patient has been disease-free for less than 5 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix, or incidental prostate cancer.
3)Uncontrolled diabetes mellitus (HbA1c > 9%)
4)Autoimmune disease other than vitiligo or past thyroiditis under substitutive hormone therapy: Patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn?s Disease, are excluded from this study, as are patients with a history of symptomatic disease (eg, rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [eg, Wegener?s Granulomatosis]); motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome and Myasthenia Gravis).
5)Other chronic intestinal diseases associated with diarrhea.
6)Active infection or other serious illness or medical condition.
7)Known active or chronic infection with HIV, Hepatitis B, or Hepatitis C.
8)Treatment with any of the following medications: IL-2, interferon or other immunotherapies, cytotoxic chemotherapy, immunosuppressants; inhibitors of molecular targets (eg, BRAF, MEK, KIT), Or chronic use of systemic corticosteroids (for the treatment of unrelated to cancer) diseases concomitantly or within 3 weeks prior to start of treatment.
9)Any experimental therapy administered in the past 30 days prior to the beginning of the treatment.
10)Any non-cancer vaccine therapy used for the prevention of infectious diseases (up to 4 weeks before any dose of study drug).
11)Women of childbearing potential (WOCBP), as defined above in 'Inclusion criteria', who:
a. are unwilling or unable to use an acceptable method of contraception to avoid pregnancy for their entire study period and for at least 26 weeks after cessation of study drug, or
b. have a positive pregnancy test at baseline, or
c. are pregnant or breastfeeding.
12)Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (eg, infectious) illness.
13)Any other general, medical or psychological conditions which in the opinion of the investigator will make the administration of ipilimumab hazardous, or that would preclude appropriate informed consent or compliance with the protocol, or obscure the interpretation of eventual AEs.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Efficacy - Primary endpoint: 1-year survival rate;Secondary Objective: 1) Efficacy - Endpoints: <br>a) Progression-Free survival-PFS (median, 6-month PFS rate)<br>b) Intracranial PFS (median, 6-month PFS rate)<br>c) Extracranial PFS (median, 6-month PFS rate)<br>2) Overall survival (median)<br>3) Response rate: (global, intracranial, extracranial) (?Immune-related response criteria?)<br>4) Safety: Adverse Event rates<br>5) Feasibility: dose delays/reductions, treatment exposure;Primary end point(s): The primary endpoint will be 1-year survival rate.;Timepoint(s) of evaluation of this end point: Survival status will be assessed after 1 year since the start of therapy
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1) Efficacy-Endpoints: <br>a) Progression-Free survival-PFS (median, 6-month PFS rate)<br>b) Intracranial PFS (median, 6-month PFS rate)<br>c) Extracranial PFS (median, 6-month PFS rate)<br>d) Overall survival (median)<br>e) Response rate: (global, intracranial, extracranial) (Immune-related response criteria)<br>2) Safety: Adverse Event rates<br>3) Feasibility: dose delays/reductions, treatment exposure;Timepoint(s) of evaluation of this end point: Efficacy: Tumor response evaluations will be performed baseline, D30C4 +/- 2 days, every 3 months +/- 1 week until disease progression.<br><br>Safety: Safety Assessments will be evaluated for all treated subjects in each visit, using the NCI CTC (Common Toxicity Criteria) version 4.0.<br><br>Feasibility: dose delays/reductions, treatment exposure in each visit