| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 8.0 |
| E.1.2 | Level | VTc |
| E.1.2 | Classification code | 10025650 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
Main objective:
To assess the anti-tumor efficacy, as determined by objective response rate, of intravenous ticilimumab administered at a dose of 15 mg/kg every 90 days to patients with relapsed or refractory advanced melanoma.
|
|
| E.2.2 | Secondary objectives of the trial |
Secondary objectives:
To assess additional evidence of anti-tumor activity as measured by best on-study response rate, durable response rate, duration of response, progression-free survivial, and overall survival
To further characterize the safety profile and tolerability of ticilimumab in these settings
To further characterize the pharmacokinetics (PK) of ticilimumab
To identify any human antihuman antibody (HAHA) response to ticilimumab
To explore whether the cytotoxic T lymphocyte-associated antigen 4 (CTLA4), FcgammaRIIa and IgG2a genotypes influence the safety, immune response and or efficacy of patients treated with ticilimumab
To explore the relationships between clinical response (efficacy or toxicity) and tumor or blood genomics
To explore health-related quality-of-life outcomes (HQoL) and satisfaction with treatment
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
To be eligible for the study, patients must satisfy all of the following criteria:
1. Histologically confirmed melanoma that is surgically incurable and either:
• Stage III melanoma (AJCC 6th edition) including locally relapsed, in-transit lesions or draining nodes OR
• Stage IV melanoma (M1a, M1b or M1c)
2. Prior treatment must include at least one systemic therapy for the treatment of metastatic disease. Prior systemic regimen for the treatment of metastatic melanoma must contain interleukin-2, dacarbazine and/or temozolamide or interferon-alfa. Patient must have received at least one cycle at full dose.
3. Documented disease progression after the last dose of prior therapy. Previously treated patients will include patients whose disease progressed during previous treatment (refractory), recurred following previous treatment (relapsed) or patients who could not tolerate previous treatment due to unacceptable toxicity and subsequently progressed (see Section 4.3.1).
4. A minimum of one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST). Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension with longest diameter 2.0 cm using conventional techniques or >1.0 cm with spiral CT scan. Skin lesions documented by color photography must have a longest diameter of at least 1.0 cm. If the measurable disease is restricted to a solitary lesion, its neoplastic nature must be confirmed by cytology or histology. Clinically detected lesions will only be considered measurable when they are superficial (eg, skin nodules) and the longest diameter is >2 cm. Palpable lymph nodes >2.0 cm should be demonstrable by CT scan. Tumor lesions that are situated in a previously irradiated area will be considered measurable if progression is documented following completion of radiation therapy.
NOTE: As a point of clarification for this study, skin lesion(s) selected as target lesions will be accurately measured, and longest diameter will be at least 1.0 cm. Care should be exercised during biopsy procedures to prevent the alteration of the longest diameter of the selected skin lesion(s). Documentation by color photography, including a ruler to document the size of the target lesion(s), is required.
5. ECOG performance status (PS) 0 or 1 (see Appendix B).
6. Age >18 years.
7. Adequate bone marrow, hepatic, and renal function determined within 14 days prior to enrollment, defined as:
• Absolute neutrophil count >1.5 x 109 cells/L
• Platelets >100 x 109/L
• Hemoglobin >10 g/dL
• Aspartate and alanine aminotransferases (AST, ALT) <2.5 x ULN (<5 x ULN, if documented liver metastases are present)
• Total bilirubin <2 x ULN (except patients with documented Gilbert’s syndrome)
• Serum creatinine >2.0 mg/dL or calculated creatinine clearance 60 mL/min
8. Serum lactic acid dehyrdrogenase (LDH) >2 x ULN
9. Patients must have recovered from all prior treatment-related toxicities, to baseline status, or to NCI CTCAE (v 3.0) Grade of 0 or 1, except for toxicities not considered a safety risk such as alopecia or residual peripheral neuropathy resulting from prior systemic therapy. Post surgical pain shall not be considered a basis for exclusion.
10. Must be willing and able to provide written informed consent.
|
|
| E.4 | Principal exclusion criteria |
Patients presenting with any of the following will not be included in the study:
1. Diagnosed with melanoma of ocular origin (uveal melanoma).
2. Received treatment for cancer, including immunotherapy, within one month prior to enrollment (dosing).
3. Received any prior vaccine therapy for the treatment of melanoma within the last 6 months. If received last dose of vaccine prior to 6 months patient is eligible.
4. Received any prior CTLA4-inhibiting agent.
5. Previously randomized to Pfizer study A3671009: A Phase 3, Open Label, Randomized Comparative Study of CP 675,206 and Either Dacarbazine or Temozolomide in Patients with Advanced Melanoma.
6. History of, chronic autoimmune disease (eg, Addison’s disease, multiple sclerosis, Graves disease, Hashimoto’s thyroiditis, inflammatory bowel disease, psoriasis, rheumatoid arthritis, systemic lupus erythematosus, hypophysitis, etc.). Active vitiligo or a history of vitiligo will not be a basis for exclusion.
7. Known active or chronic viral hepatitis.
8. History of inflammatory bowel disease, celiac disease, or other chronic gastrointestinal conditions associated with diarrhea or current acute colitis of any origin.
9. History of uveitis or melanoma-associated retinopathy.
10. Potential requirement for systemic corticosteroids or concurrent immunosuppressive drugs based on prior history or received systemic steroids within the last 4 weeks prior to enrollment (Note: inhaled or topical steroids in standard doses are allowed).
11. Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol.
12. Any serious, uncontrolled medical disorder or active infection, which would impair their ability to receive study treatment. (Note that patients with evidence of Acquired Immunodeficiency Syndrome [AIDS] are excluded).
13. Brain metastases. Radiological documentation of absence of brain metastases at screening is required for all patients. (Note that a history of treated brain mets is acceptable.)
14. History of other malignancies, except for adequately treated basal cell carcinoma or squamous cell skin cancer or carcinoma of cervix, unless the patient has been disease-free for at least 5 years.
15. Pregnancy or breast-feeding. Female patients must be surgically sterile or be postmenopausal for two years, or must agree to use effective contraception during the period of treatment and 12 months after. All female patients with reproductive potential must have a negative pregnancy test (serum/urine) within 72 hours prior to enrollment. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Best Overall Response (BR) based on Response Evaluation Criteria in Solid Tumors (RECIST), and defined as the proportion of patients with a confirmed complete (CR) or partial response (PR) relative to the total number of evaluable patients. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Information not present in EudraCT |
| E.6.2 | Prophylaxis | Information not present in EudraCT |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | Information not present in EudraCT |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| Health-related quality pf life (HQoL) and anti-human antibody to ticilimumab (HAHA) |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
| E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Information not present in EudraCT |
| E.8.1.3 | Single blind | Information not present in EudraCT |
| E.8.1.4 | Double blind | Information not present in EudraCT |
| E.8.1.5 | Parallel group | Information not present in EudraCT |
| E.8.1.6 | Cross over | Information not present in EudraCT |
| E.8.1.7 | Other | Information not present in EudraCT |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| Please refer to the Protocol |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 24 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 24 |
Print
