THE IPI - Trial in Advanced Melanoma: Melanoma Patients With Advanced Disease

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2012
• Main ID: NCT01355120
• Date of registration: 29/12/2010
• Primary sponsor: Prof. Dr. med. Dirk Schadendorf
• Public title: THE IPI - Trial in Advanced Melanoma: Melanoma Patients With Advanced Disease DeCOG
• Scientific title: THE IPI - Multibasket Trial in Advanced Melanoma: Prospective Clinical Phase II Multibasket Study in Melanoma Patients With Advanced Disease (DeCOG MM-PAL11)
• Date of first enrolment: October 2011
• Target sample size: 41
• Recruitment status: Active, not recruiting
• URL: http://clinicaltrials.gov/show/NCT01355120
• Study type: Interventional
• Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Countries of recruitment

Germany

Contacts

• Name: Dirk Schadendorf, Professor
• Affiliation: University Hospital, Essen

Key inclusion & exclusion criteria

Inclusion Criteria

Patients meeting all of the following criteria will be considered for admission to the
trial:

1. Histologically proven ocular melanoma

2. Measurable disease according to RECIST in unresectable stage III-IV

3. Minimum age of 18 years,

4. Able and willing to give valid written inform consent

5. Patients with or without prior systemic treatment for advanced malignant melanoma are
eligible .

6. In case of systemic pre-treatment, an interval of at least 28 days since treatment
with chemotherapy, biochemotherapy, surgery, radiation, or immunotherapy is mandatory
as well as recovery from any clinically significant toxicity experienced during
treatment is recommended. Prior treatment must be completed by the time of ipilimumab
administration. Palliative radiation therapy outside of the brain or therapeutic
radiation to the brain after the patient's condition is stabilized and systemic
steroids required for the management of symptoms due to brain metastases is decreased
to the lowest fixed dose possible and does not require the 28-day waiting period.
Patient must have recovered from any acute toxicity associated with prior therapy.

7. Expected survival of at least six months

8. ECOG Performance Status 0, 1 or 2.

9. Within the last 2 weeks prior to study day 1 the following laboratory parameters,
which should be within the ranges specified:

Lab Parameter Range White blood cells (WBC) >= 2500/mm3 (= 1 2.5 x 109/L) Absolute
neutrophil count (ANC) >= 1000/mm3 (= 1.0 x 109/L) Platelets =75.000/mm3 (= 75 x
109/L) Hemoglobin = 9 g/dL (= 90 g/L; may be transfused) Creatinine <= 2.0 x ULN
Bilirubin total <= 2.0 x ULN (excepted patients with Gilbert's Syndrome, who must
have a total bilirubin less than 3.0 mg/dL) <= 5 x ULN for patients with liver
metastases

10. No childbearing potential or negative pregnancy test of women of childbearing
potential performed within 7 days prior to the start of treatment.

Women of childbearing potential (WOCP) 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 26 weeks 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 26 weeks
after the last dose of investigational product, in such a manner that the risk of
pregnancy is minimized.

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.

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.

WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or
equivalent units of HCG) at Baseline within 7 days before the start of ipilimumab and at
week 12.

Exclusion Criteria

Patients will be excluded from the study for any of the following reasons:

1. The patient requires concomitant therapy with any of the following: IL 2, interferon,
or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive
agents; other investigation therapies; any other systemic therapy for cancer
including any other experimental treatment.

2. The patient requires chronic use of systemic corticosteroids. Systemic steroids for
management of symptoms due to brain mets should be avoided if possible or subject
should be stable on the lowest clinically effective dose. Topical or inhalational
steroids are permitted.

3. Use of any investigational or non-registered product (drug or vaccine) other than the
study treatment.

4. Active autoimmune disease: 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. Symptomatic CNS metastases (Remark: Asymptomatic stable, untreated or pretreated
central nervous system (CNS) metastasis are allowed)

6. Family history of congenital or hereditary immunodeficiency.

7. The patient is known to be positive for Human Immunodeficiency Virus (HIV) or other
chronic infections (HBV, HCV) or has another confirmed or suspected immunosuppressive
or immunodeficient condition.

8. The patient has psychiatric or addictive disorders that may compromise his/her
ability to give informed consent or to comply with the trial procedures.

9. Lack of availability for clinical follow-up assessments.

10. The patient has concurrent severe medical problems, unrelated to the malignancy, that
would significantly limit full compliance with the study or expose the patient to
unacceptable risk.

11. Other serious illnesses, e.g., serious infections requiring antibiotics or bleeding
disorders.

12. Patients with serious intercurrent illness, requiring hospitalization.

13. For female patients: the patient is pregnant or lactating. Women of childbearing
potential: Refusal or inability to use effective means of contraception

14. Any underlying medical or psychiatric condition, which in the opinion of the
investigator will make the administration of ipilimumab hazardous or obscure the
interpretation of AEs, such as a condition associated with frequent diarrhea.

15. Subjects with melanoma who have another active, concurrent, malignant disease are not
eligible for this trial, with the exception of adequately treated basal or squamous
cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix.

16. Previous treatment with ipilimumab



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Ocular Melanoma

Intervention(s)

Drug: Ipilimumab

Primary Outcome(s)

Overall survival [Time Frame: alive 12 months after date from the first study drug adminstration]

Secondary Outcome(s)

Efficacy according RECIST criteria [Time Frame: 12 months after date from the first study drug administration]

Efficacy according to immune-related response criteria (ir-RC) at any time during treatment [Time Frame: 12 months after date from the first study drug administration]

Overall survival at 1 year in the subgroups (cutaneous, uveal, mucosal) [Time Frame: 12 months after date from the first study drug administration]

Progression free survival rate at 6 months [Time Frame: 6 months after date from the first study drug administration]

safety and efficacy parameters [Time Frame: 12 months after date from the first study drug adminstration]

To evaluate possible surrogate markers in peripheral blood and tumour biopsy (translational research program) [Time Frame: 12 weeks after date from the first study drug administration]

To examine the value of peripheral blood absolute lymphocyte count (ALC) as a predictive biomarker in various patient cohorts with unresectable stage III-IV melanoma treated with ipilimumab monotherapy [Time Frame: 12 weeks after date from the first study drug administration]

To explore clinical efficacy of ipilimumab in relation to b-raf mutation status, brain metastases, LDH, HLA-A2 status [Time Frame: 12 months after date from the first study drug administration]

Secondary ID(s)

DeCOG -MM-PAL11

Source(s) of Monetary Support

Please refer to primary and secondary sponsors