E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
OVARIAN CANCER (SECOND OR THIRD COMPLETE REMISSION) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
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 for this study is as follows: • To estimate the clinical benefit of the addition of GDC-0449 as maintenance therapy for patients with ovarian cancer in a second or third complete remission, as measured by investigator-determined PFS by radiographic assessment |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives for this study are as follows: • To make a preliminary assessment of the safety and tolerability of GDC-0449 in this population • To evaluate the relationship between detectable Hh expression in archival tumor tissue and clinical benefit of GDC-0449 in patients as measured by PFS • To make a preliminary assessment of the efficacy of GDC-0449 as measured by overall survival
Exploratory objectives for this study are as follows: • To explore the effect of Hh expression in archival tumor tissue on secondary endpoints • To explore the effect of Hh pathway signaling on primary and secondary endpoints • To explore the effect of GDC-0449 on PFS as assessed by a combination of CA-125 and radiographic criteria |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Study Title: DNA REPOSITORY SUBSTUDY IN ASSOCIATION WITH GDC-0449 STUDY SHH4489g
Protocol Date and Version: SHH4489g dated 01 May 2009
The primary objective of this study is to perform exploratory analyses to generate hypotheses identifying genes associated with treatment response, toxicity, or disease risk. If such genetic hypotheses are identified, they may be tested in future clinical studies within this therapeutic area.
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E.3 | Principal inclusion criteria |
Patients must meet the following inclusion criteria to be eligible for study entry: • Age ≥ 18 years • Histologic diagnosis of epithelial ovarian carcinoma, primary peritoneal carcinoma, or fallopian tube carcinoma • Must be in second or third complete remission, have received chemotherapy (platinum-based and/or non−platinum-based) for recurrent disease, and have achieved a complete remission after their most recent chemotherapy regimen Complete remission is defined as no symptoms suggestive of persistent cancer, CT scan of the chest/abdomen/pelvis without evidence of ovarian cancer within 4 weeks of randomization, and normal CA-125 (measured within 2 weeks of randomization) following completion of prior chemotherapy. The study investigator should confirm the status of disease remission by CT scan before patient enrollment. If patient has lymphadenopathy by CT scan and the investigator thinks that it is unlikely due to ovarian cancer, this patient is considered eligible. If indicated, a confirmatory biopsy should be performed. • Patients must have completed their most recent dose of cytotoxic chemotherapy regimen (platinum-based or non-platinum based) no less than 3 weeks and no more than 14 weeks prior to randomization. • Archival tissue must be available and requested. The tissue must consist of representative tumor specimens in paraffin blocks (preferred) or at least 15 unstained slides, with an associated pathology report, obtained at any time prior to entry of study. Archival tissues are to be sent as soon as possible. • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (see Appendix D) • Adequate hematopoietic capacity, as defined by the following: Hemoglobin > 8.5 g/dL, not transfusion-dependent Granulocyte count ≥ 1200/μL Platelets ≥ 75,000/μL • Adequate hepatic function, as defined by the following: AST and ALT ≤ 3 × the upper limit of normal (ULN) Total bilirubin ≤ 1.5 × ULN or within 3 × ULN for patients with Gilbert’s disease • Adequate renal function, as defined by the following: Serum creatinine ≤ 2.0 mg/dL or calculated creatinine clearance > 50 mL/minute • Negative serum or urine pregnancy test on Day 1 • For women of childbearing potential: Use of two effective methods of barrier contraception, including one barrier method (See Appendix C for acceptable and unacceptable methods of contraception.) • Signed informed consent |
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E.4 | Principal exclusion criteria |
Patients who meet any of the following criteria will be excluded from study entry: • Pregnancy or lactation For women of childbearing potential: use of two effective methods of barrier contraception, including one barrier method, during the study and for 12 months after discontinuing study drug (see Appendix C for acceptable and unacceptable methods of contraception). • Patients whose ovarian cancer is in first remission • Patients must not have experienced more than two prior recurrences of disease • Concurrent non−protocol-specified anti-tumor therapy, either approved or unapproved (e.g., chemotherapy, hormonal therapy, other targeted therapy, radiation therapy, surgery, herbal therapy). Hormonal replacement therapies for treatment of postmenopausal symptoms do not exclude patients from this study. • Current, recent (within 4 weeks of Day 1), or planned participation in an experimental drug study while enrolled in this study • History of other malignancies within 3 years of Day 1, except for tumors with a negligible risk for metastasis or death, such as adequately treated BCC or squamous-cell carcinoma of the skin; ductal carcinoma in situ of the breast; or carcinoma in situ of the cervix • Uncontrolled medical illnesses such as infection requiring IV antibiotics • Life expectancy < 12 weeks • History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or that might affect interpretation of the results of the study or render the patient at high risk from treatment complications. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint in this study is the hazard ratio (HR) of PFS using the stratified Cox model. PFS will be defined as the time from randomization until the first occurrence of radiographic progression or death from any cause, determined by the investigator (see Primary Efficacy Outcome Measures, Section 3.3.1, for a definition of radiographic progression). Patients who do not meet the criteria for disease progression, but who die, will be treated as having progressed for the PFS analysis. Patients who do not meet the criteria for disease progression and who do not die will be censored at the time of last tumor assessment. |
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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 | Information not present in EudraCT |
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 | 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) | 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 | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
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.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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 | No |
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
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Treatment will continue until evidence of radiographic progression, until the patient experiences intolerable toxicities most probably attributable to GDC-0449, or until the patient withdraws from the study.
Patients who discontinue study treatment will be followed for survival approximately every 3 months until death, loss to follow-up, or study termination by Genentech. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |