| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Persistent or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Carcinoma |
|
| E.1.1.1 | Medical condition in easily understood language |
| Cancer of the ovary, fallopian tube or lining of the abdominal cavity. |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10033128 |
| E.1.2 | Term | Ovarian cancer |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10066697 |
| E.1.2 | Term | Ovarian cancer recurrent |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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 in this study, in patients with persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma, is to jointly determine the following two rates: progression-free survival rate at 6 months (PFS-6) and objective response rate (ORR) |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to determine separately:
• Safety and tolerability
• Progression-free survival (PFS)
• Overall survival rate at 1 year (OS-1)
• Overall survival (OS)
• Progression-free survival rate at 6 months (PFS-6)
• Objective response rate (ORR) |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. The patient has recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. Histologic documentation of the original primary tumor is required via a pathology report.
2. The patient has at least one unidimensionally-measurable target lesion (≥ 2 cm with conventional techniques, or ≥ 1 cm by spiral computed tomography [CT] or magnetic resonance imaging [MRI]), as defined by Response Evaluation Criteria in Solid Tumors (RECIST). Tumors within a previously irradiated field will be designated as “nontarget” lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy.
3. The patient has recovered to Grade ≤ 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0 (NCI-CTCAE v3.0) from the effects of recent surgery, radiotherapy, chemotherapy, hormonal therapy, or other targeted therapies for ovarian cancer, with the exception of alopecia or peripheral neuropathy (which must have resolved to Grade ≤ 2). Any other prior therapy directed at the malignant tumor must be discontinued at least three weeks prior to the first dose of study medication, or hormonal therapy discontinued at least one week prior to the first dose of study medication. Continuation of hormone replacement therapy is permitted.
4. The patient has completed at least one platinum-based chemotherapeutic regimen for management of primary disease, and must have at least one of the following: a platinum-free interval of < 12 months after the final dose of primary platinum-based therapy, progression during platinum-based therapy, or persistent disease after platinum-based therapy.
5. The patient has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1 at study entry.
6. The patient has adequate hematological functions (absolute neutrophil count [ANC] ≥ 1200 cells/μL, hemoglobin ≥ 9 g/dL, and platelets ≥ 100,000 cells/μL).
7. The patient has adequate hepatic function (bilirubin ≤ 1.5 times the upper limit of normal [ULN]; aspartate transaminase [AST] and/or alanine transaminase [ALT] ≤ 3.0 times ULN, or ≤ 5.0 times ULN if the transaminase elevation is due to liver metastases).
8. The patient has adequate renal function (serum creatinine ≤ 1.5 x ULN or creatinine clearance [measured or calculated] ≥ 60 mL/min).
9. The patient’s urinary protein is ≤ 1+ on dipstick or routine urinalysis (UA). If urine dipstick or routine analysis indicated ≥ 2+ proteinuria, then a 24-hour urine must be collected and must demonstrate < 1000 mg of protein in 24 hours to allow participation in the study.
10. The patient has adequate coagulation function, as defined by international normalized ratio (INR) ≤ 1.5 and a partial thromboplastin time (PTT) ≤ 1.5 X ULN if not receiving anticoagulation therapy. Patients on full-dose anticoagulation must be on a stable dose of oral anticoagulant or low molecular weight heparin, and if on warfarin must have therapeutic INR and have no active bleeding (defined as within 14 days of first dose of study medication) or pathological condition that carries a high risk of bleeding (eg, tumor involving major vessels or known varices).
11. For patients who have received anthracycline therapy, the left ventricular ejection fraction (LVEF) must be within normal institutional range by a pretreatment echocardiogram or multigated acquisition (MUGA) scan.
12. If sexually active, the patient is post-menopausal, surgically sterile, or using effective contraception in the opinion of the investigator.
13. The patient is ≥ 18 years of age.
14. The patient has a life expectancy of ≥ 3 months.
15. The patient is able to provide informed written consent and is amenable to compliance with protocol schedules and testing.
|
|
| E.4 | Principal exclusion criteria |
1. The patient has a concurrent active malignancy, other than adequately treated nonmelanomatous skin cancer or other noninvasive carcinoma or in situ neoplasm. A patient with previous history of malignancy is eligible provided that she has been disease-free for > 3 years.
2. The patient has received a noncytotoxic regimen (usually called targeted therapy such as bevacizumab) for recurrent or persistent disease. (Patients may have received a noncytotoxic regimen as primary treatment.)
3. The patient has received radiotherapy for the treatment of ovarian, fallopian tube, or primary peritoneal cancer within 3 weeks (21 days) prior to the first dose of study medication.
4. The patient has received prior radiotherapy to any portion of the abdominal cavity or pelvis other than for the treatment of ovarian, fallopian tube, or primary peritoneal cancer within the last 3 years. (Prior radiation for localized cancer [eg, of the breast, head and neck, or skin] is permitted, provided that it was completed > 3 years prior to the first dose of study medication, and the patient remains free of recurrent or metastatic disease.)
5. The patient has received prior chemotherapy for any abdominal or pelvic tumor, other than for the treatment of ovarian, fallopian tube, or primary peritoneal cancer < 3 years prior to the first dose of study medication. Prior adjuvant chemotherapy for localized breast cancer is permitted, provided that it was completed >3 years prior to the first dose of study medication, and that the patient remains free of recurrent or metastatic disease.
6. The patient has undergone major abdominal surgery within 4 weeks (28 days) prior to first dose of study medication.
7. The patient has a suspected impending bowel obstruction, based on clinical or radiographic criteria.
8. The patient has received any hormonal therapy directed at the malignant tumor discontinued therapy within 1 week (7 days) prior to first dose of study medication.
9. The patient has received any other prior therapy directed at the malignant tumor, including immunologic agents, within 3 weeks (21 days) prior to first dose of study medication.
10. The patient has received previous treatment with IMC-1121B.
11. The patient has participated in clinical trials of experimental agents within 4 weeks (28 days) prior to first dose of study medication.
12. The patient has a history of uncontrolled hereditary or acquired bleeding or thrombotic disorders.
13. The patient has an ongoing or active infection requiring systemic antibiotics, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, myocardial infarction < 6 months, Grade ≥ 2 peripheral vascular disease, poorly controlled hypertension despite standard medical management poorly controlled thrombotic or hemorrhagic disorder, psychiatric illness or social situations that would limit compliance with study requirements, or any other serious uncontrolled medical disorders in the opinion of the investigator.
14. The patient has any history of brain metastases or leptomeningeal disease. Screening for CNS involvement for testing asymptomatic patients is not required.
15. The patient has known human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness.
16. The patient is pregnant (confirmed by serum beta human chorionic gonadotropin [β-HCG] test) or lactating. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Joint Primary Efficacy Endpoints - PFS-6 (the proportion of patients that at 6 months into the study show no evidence of disease progression or death from any cause) and ORR (Objective response rate- calculated as the number of patients who achieve a best confirmed response (CR or PR), divided by the total number of patients in the efficacy population). |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
PFS-6 - 6 months
ORR - end of study |
|
| E.5.2 | Secondary end point(s) |
The following additional efficacy parameters will be considered for separate analysis:
• Progression-free survival (PFS)
• Overall survival rate at 1-year (OS-1)
• Overall survival (OS)
• Progression-free survival rate at 6 months (PFS-6)
• Objective response rate (ORR)
Safety Endpoints
- Adverse Event
- Laboratory Results
- Vital Signs
- Physical Examination |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
• PFS - first evidence of progression or death
• OS-1 - at 1 year
• OS - at time of death
• PFS-6 - at 6 months
• ORR - end of study
Safety Endpoints will be measured at various points throughout the study. |
|
| 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 | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| 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 | No |
| 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) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Information not present in EudraCT |
| E.8.2.4 | Number of treatment arms in the trial | 1 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.5.1 | Number of sites anticipated in the EEA | 1 |
| 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 | No |
| 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 |
| United Kingdom |
| United States |
|
| 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
|
* Sufficient data have been collected for final analysis of the primary endpoint;
and
* The last patient has discontinued study treatment and completed the 30-day safety follow-up visit (or all adverse events considered at least possibly related to study therapy or that caused discontinuation of treatment have been followed until the event has resolved, stabilized, returned to baseline, or deemed irreversible |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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