E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066697 |
E.1.2 | Term | Ovarian cancer recurrent |
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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 |
The primary objective of the study is to determine the composite response (measured by best overall response [CR + PR] or PFS at 24 weeks) in subjects with recurrent ovarian cancer who receive single-agent 15 mg/kg CNTO 888 IV formulation administered as a 90-minute infusion once every 2 weeks. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are to evaluate safety and additional efficacy (objective response rate [CR + PR], PFS, CA 125 response rate, and overall survival), pharmacology (pharmacokinetics and pharmacodynamics), and immunogenicity of single-agent CNTO 888 in subjects with recurrent ovarian cancer. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Potential subjects must satisfy all of the following criteria to be enrolled in the study: • Women age ≥ 18 years • Sign an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study • Histological documentation of epithelial ovarian or Fallopian tube cancer, or primary peritoneal cancer of serous, endometrioid, or clear cell subtypes • Received at least 1 prior complete 6-cycle platinum-containing chemotherapy regimen and no more than 3 regimens of chemotherapy in total • Recurrence or progression after platinum-based treatment for ovarian cancer defined according to the following subsets: − Group A: Relapse-free interval after all prior platinum-based treatment of > 6 months and who are not candidates for further platinum therapy due to a hypersensitivity to platinum or for other reasons − Group B: Relapse-free interval after the first or any subsequent platinumbased treatment of < 6 months • Measurable disease at baseline according to RECIST guidelines • Subjects in Group B must be willing and able to have pretreatment and posttreatment biopsies (see Section 4.4) • ECOG performance status during screening and immediately prior to the first dose of study agent: (Attachment 3) − Status of 0, 1, or 2 for subjects who have had only 1 prior chemotherapy regimen − Status of 0 or 1 for subjects who have had more than 1 chemotherapy prior regimen • Adequate bone marrow, liver, and renal function within 2 weeks prior to the first dose of study agent as described below: − Hemoglobin ≥ 9.0 g/dL (5.6 mmol/L; 90 g/L) without transfusion dependency or erythropoiesis-stimulating agents − Absolute neutrophil count (ANC) ≥ 1.0 x 109/L (1000/mm3) without hematopoietic cytokine support − Platelets ≥ 100 x 109/L (100,000/mm3) without transfusion dependency or hematopoietic cytokine support − Coagulation prothrombin time (PT) or international normalized ratio (INR), and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN − AST and ALT ≤ 3 x ULN if no liver metastasis; ≤ 5 x ULN with liver metastasis − Total bilirubin ≤ 1.5 x ULN − Serum creatinine ≤ 1.5 x ULN • Female subjects must be postmenopausal (at least 12 months since last menses), surgically sterile, abstinent, or if sexually active and of child-bearing potential be practicing an effective method of birth control (e.g., prescription or oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilization) before study entry and throughout the study; have a negative urine pregnancy test at screening. • Willing/able to adhere to the prohibitions and restrictions specified in this protocol • To participate in the optional pharmacogenomic component of this study, subjects must have signed the informed consent form for pharmacogenomic research indicating willingness to participate in the pharmacogenomic component of the study (where local regulations permit). Refusal to give consent for this component does not exclude a subject from participation in the clinical study. |
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E.4 | Principal exclusion criteria |
Potential subjects who meet any of the following criteria will be excluded from participating in the study: • Tumors of malignant mixed mesodermal types or primary mucinous tumors of the ovary • Subjects who have refractory disease (relapsed disease during any prior platinumbased chemotherapy regimen) • Subjects with a relapse-free interval of > 12 months after the most recent platinumbased treatment • Known or symptomatic CNS metastases • Requires parenteral hydration or nutrition; has evidence of bowel obstruction; a history of abdominal fistula, gastrointestinal perforation or bleeding, or intra-abdominal abscess • Presence of or at high risk for intestinal obstruction by, or transluminal intestinal growth of, ovarian cancer or any concurrent malignancy • Residual toxicities resulting from previous therapy that are ≥ Grade 2 (except for alopecia) • Known allergies, hypersensitivity, or intolerance to CNTO 888 or its excipients (refer to Section 14.1, Physical Description of Study Drug) or clinically significant reactions to chimeric or human proteins • Bleeding diathesis or requires concurrent therapeutic dose of anticoagulation (lowdose prophylaxis is permitted to maintain IV line patency) • Received an investigational drug/agent (including vaccines), intraperitoneal cancer therapy, local radiotherapy or used an investigational medical device within 4 weeks prior to the first dose of study agent or are currently enrolled in an investigational study • Concomitant treatment such as, immunotherapy, biotherapy, radiotherapy, chemotherapy, investigative therapy, or new steroid therapy (see Section 8 for more details) • Requires transfusion of blood products to meet eligibility criteria, or within 4 weeks prior to the collection of screening hematology laboratory sample • Uncontrolled infection, clinically important active infection within 4 weeks prior to the first dose of study agent, currently receiving treatment for an infection, known to be seropositive for HIV, or known active hepatitis A, B, or C infection • Major surgery, medical or surgical interference with the peritoneum or pleura or significant traumatic injury within 4 weeks prior to the first dose of study agent, or planning to have surgery (except for minor surgical procedures) during the study, or planned major surgery within 8 weeks after the last dose of study agent. Laparoscopy is allowed. • Serious concurrent illness (medical or psychiatric), altered mental status (eg, dementia) or any uncontrolled medical condition (eg, uncontrolled diabetes), including the presence of laboratory abnormalities, that places the subject at unacceptable risk by participating in the study, limits full compliance, or confounds the ability to interpret data from the study or that, in the opinion of the investigator, would compromise the well-being of the subject or the study or prevent the subject from meeting or performing study requirements • Subjects on antiplatelet therapy who have a bare metal or drug-eluting coronary stent or with active angina pectoris or New York Heart Association (NYHA) Class III or IV heart disease. Significant cardiac disease characterized by significant ischemic coronary disease, significant arrhythmias, or congestive heart failure (greater than or equal to NYHA Class II) or myocardial infarction within 6 months prior to the first dose of study agent (see Attachment 4) • Transplanted solid organ and receiving immunosuppressive therapy (with the exception of a corneal transplant that was performed ≥ 12 weeks prior to screening) • Active or symptomatic autoimmune disorders or requiring treatment within the last 5 years (eg, rheumatoid arthritis, Crohn’s disease, systemic lupus, or multiple sclerosis) • Prior or concomitant malignancy (other than ovarian cancer) 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 or prior treatment with a platinum-based therapy for a non-ovarian cancer indication • Pregnant or breast-feeding |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the composite response rate. The composite response rate will be estimated and its 2-sided exact 95% confidence interval will be computed. A subject has a composite response if 1 of the following responses occurs after the first dose of study agent: • CR or PR according to RECIST guidelines • Disease has not progressed at 24 weeks according to RECIST guidelines |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
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 | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
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 |
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E.8.7 | Trial has a data monitoring committee | Yes |
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
|
The end of study is defined as 1 year after the last subject on study receives the last CNTO 888 treatment. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |