| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Recurrent Epithelial Ovarian Cancer and Other Solid Tumors |
|
| E.1.1.1 | Medical condition in easily understood language |
| Cancer on the surface of the ovary and other solid tumors |
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| 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 | 16.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10049280 |
| E.1.2 | Term | Solid tumour |
| 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 | 16.0 |
| 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 phase 2 objective of this study is to determine progression free survival (PFS) evaluated by the investigator of 2 different schedules of OSI-906 (Arm A and B) in combination with weekly paclitaxel as compared with paclitaxel alone (Arm C) in recurrent/refractory ovarian cancer patients.
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|
| E.2.2 | Secondary objectives of the trial |
The secondary phase 2 objectives of this study are to evaluate in parallel for OSI-906 and paclitaxel and paclitaxel alone:
- objective response rate (ORR) using RECIST v1.1, CA-125 response rate, duration of response (RECIST v1.1), duration of CA-125 response, and overall survival (OS);
- the safety profile of the combination of OSI-906 and paclitaxel;
- relevant pharmacodynamic markers involved in related pathways; and
- exploratory biomarkers related to treatment outcomes and/or histologic characterization. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Patients must meet all of the following inclusion criteria to be eligible for participation in this study.
1. Histologically or cytologically confirmed epithelial ovarian carcinoma. Patients with fallopian or peritoneal cancer will also be eligible. Patients with any solid tumor that may be treated with weekly paclitaxel will be eligible for the phase 1 portion.
2. For the phase 2 portion, patients must have radiologically-confirmed progressive disease by RECIST v1.1 criteria within 6 months prior to randomization (patients must have measurable disease according to RECIST v1.1).
3. Age >/=18 years.
4. ECOG PS 0 – 1 (Appendix 13 2).
5. Predicted life expectancy >/= 12 weeks.
6. Patients may have had prior therapy, providing the following
conditions are met:
a. Chemotherapy: Prior chemotherapy must have been completed at least 3 weeks prior to study enrollment (6 weeks for mitomycin C, nitrosoureas or high-dose carboplatin [>/= 600 mg/m²] and 4 weeks for investigational drugs) and the patient should have recovered from any drug-related toxicities (with the exception of grade 1 neuropathy and or alopecia).
Phase 1 – While there is no limit on the number of prior regimens for patients entered into the phase 1 portion, any prior taxane therapy must have been administered on a 3 week schedule.
Phase 2 – Patients must have received prior chemotherapy, which must have contained a platinum and a taxane at some point. Any prior taxane therapy must have been administered on a 3 week schedule. A maximum of 2 prior chemotherapy regimens are permitted. Patients must be refractory (radiologically confirmed by CT scan PD during chemotherapy) or resistant (radiologically confirmed by CT scan PD within six months of completing chemotherapy) to their last platinumcontaining chemotherapy regimen.
b. Radiation: Patients may have had prior radiation therapy provided they have recovered from the acute, toxic effects of radiotherapy prior to registration/randomization. A minimum of 21 days must have elapsed between the end of radiotherapy and registration/randomization into the study unless the radiation affected less than 25% of bone marrow. Radiated lesions cannot be chosen as the target lesion.
c. Surgery: Previous surgery is permitted provided that adequate wound healing has occurred prior to registration/randomization.
7. Fasting glucose </= 150 mg/dL (8.3 mmol/L).
8. Adequate hematopoietic, hepatic, and renal function defined as
follows:
• Neutrophil count >/= 1.5 x 10^9/L and platelet count >/= 100 x
10^9/L;
• Bilirubin </= 1.5 x ULN;
• AST and/or ALT </= 2.5 x ULN or </= 5 x ULN if patient has
documented liver metastases; and
• Serum creatinine </= 1.5 x ULN.
9. Female patient must be either:
- Of non child bearing potential:
• post-menopausal (defined as at least 1 year without any menses) prior to Screening, or
• documented surgically sterile or status post hysterectomy (at least 1 month prior to Screening).
- Or, if of childbearing potential:
• must have a negative urine pregnancy test at Screening and
• must use two forms of birth control (at least one of which must be a barrier method) starting at Screening and throughout the study period and for 28 days [or 5 five half lives of the study drug whichever is longer] after final study drug administration. Acceptable forms include:
• Established use of oral, injected or implanted hormonal methods of contraception.
• Placement of an intrauterine device (IUD) or intrauterine system (IUS).
• Barrier methods of contraception: Condom OR Occlusive cap
(diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.
10. Female patient must not be breastfeeding at Screening or during the study period and for 28 days [or 5 five half lives of the study drug whichever is longer] after final study drug administration.
11. Female patient must not donate ova starting at Screening and
throughout the study period and for 28 days [or 5 five half lives of the study drug whichever is longer] after final study drug administration.
12. Patients must provide verbal and written informed consent to
participate in the study. |
|
| E.4 | Principal exclusion criteria |
Patients who meet any of the following exclusion criteria are not eligible for enrollment.
1. Diabetes mellitus currently requiring medication (eg, insulin or oral hypoglycemics).
2. During the phase 2 portion, patients with histology of abdominal adenocarcinoma of unknown origin or a diagnosis of a borderline ovarian tumor.
3. Previous or concurrent malignancies (excluding curatively treated basal or squamous cell carcinoma of the skin or cervical cacinoma in situ) unless the patient has been in remission for at least 3 years.
4. History of significant cardiovascular disease unless the disease is
well-controlled. Significant cardiac diseases includes second/third
degree heart block; significant ischemic heart disease; QTc interval > 450 msec at baseline; poorly controlled hypertension; congestive heart failure of New York Heart Association (NYHA) Class II or worse (slight limitation of physical activity; comfortable at rest, but ordinary physical activity results in fatigue, palpitation, or dyspnea).
5. History of arrhythmia (multifocal premature ventricular contractions [PVCs], bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) that is symptomatic or requires treatment (≥ grade 3), left bundle branch block (LBBB), or asymptomatic sustained ventricular tachycardia are not allowed. Patients with atrial fibrillation controlled by medication are not excluded. Patients with mean QTcF interval ≥ 450
msec at screening are excluded.
6. Use of drugs that have a known risk of causing Torsade de Pointes (TdP) or that have a risk of causing QT interval prolongation within 14 days prior to Day 1 dosing.
7. Use of the potent CYP1A2 inhibitors ciprofloxacin and fluvoxamine. Other less potent CYP1A2 inhibitors/inducers are not excluded.
8. History of cerebrovascular accident (CVA) within 6 months prior to registration/randomization or that is not stable.
9. Prior therapy with an IGF1R inhibitor.
10. Known or prior hypersensitivity to taxanes or drugs containing
Cremophor.
11. Gastro-intestinal abnormalities, including bowel obstruction, inability to take oral medication, requirement for intravenous (IV) alimentation, active peptic ulcer or prior surgical procedures or bowel resection affecting absorption.
12. Active infection or serious underlying medical condition (including any type of active seizure disorder within 12 months prior to registration/randomization) that would impair the ability of the patient to receive protocol treatment.
13. History of any psychiatric condition that might impair the patient's ability to understand or to comply with the requirements of the study or to provide informed consent.
14. Pregnancy or breast-feeding.
15. Symptomatic brain metastases that are not stable, require steroids, are potentially life threatening, or that have required radiation within 28 days prior to registration/randomization.
16. History of allergic reactions attributed to compounds of similar
chemical or biologic composition to the study drug.
17. Participated in any interventional clinical study or has been treated with any investigational drugs within 30 days or 5 half lives whichever is longer, prior to the initiation of Screening or during the course of the study. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary efficacy variable is progression free survival (PFS) evaluated by the investigator per RECIST v1.1.
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Progression Free Survival (PFS) Time Frame: 36 months |
|
| E.5.2 | Secondary end point(s) |
| The second efficacy variables include objective response rate per RECIST v1.1 (ORR), CA- 125 response rate, duration of response (RECIST DOR), duration of CA-125 response (CA-125 DOR), and overall survival (OS). |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Objective Response Rate, Cancer Antigen 125 (CA125) Response Rate, Duration of Response, duration of CA-125, Time from the date of the first documented CA-125 response to the date of CA-125 progression, Overall survival, and Safety.
Time Frame: 36 months |
|
| 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 | 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) | Yes |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | Yes |
| 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 | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 23 |
| 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 |
| Canada |
| Czech Republic |
| Italy |
| Poland |
| Romania |
| Russian Federation |
| Switzerland |
| United Kingdom |
| United States |
|
| 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
|
| The end of the study will be defined when the stated objectives of the trial are able to be evaluated for the purpose of completing the final analysis, unless the study is otherwise terminated early. If any subject remains on study treatment after the end of the trial, they will be permitted to remain on treatment until radiological confirmed PD or any of the criteria for discontinuation are met. |
|
| 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 | 6 |
| 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 | 2 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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