A Study Evaluating Intermittent and Continuous OSI-906 and Weekly Paclitaxel in Patients With Recurrent Epithelial Ovarian Cancer (and Other Solid Tumors)

Sponsor

Astellas Pharma Inc (Industry)

Overall Status

Completed

CT.gov ID

NCT00889382

Collaborator

(none)

152

Enrollment

Locations

Arms

60.6

Actual Duration (Months)

3.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a multi-center, randomized, open-label, phase 1/2 study of continuous weekly paclitaxel and escalating doses of intermittent or continuous OSI-906 in patients with recurrent/relapsed ovarian and other solid tumors.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer Solid Tumors	Drug: OSI-906 Drug: Paclitaxel	Phase 1/Phase 2

Detailed Description

The phase 1 dose escalation portion will establish the maximum tolerated dose (MTD) in patients with advanced solid tumors. Once the recommended phase 2 dose (RP2D) is established for both schedules, the phase 2 study will begin. Patients with relapsed/recurrent epithelial ovarian cancer will be randomized 1:1:1 to 3 treatment groups.

Study Design

Study Type:

Interventional

Actual Enrollment :

152 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1/2 Study Evaluating Intermittent and Continuous OSI-906 and Weekly Paclitaxel in Patients With Recurrent Epithelial Ovarian Cancer (and Other Solid Tumors)

Actual Study Start Date :

Aug 5, 2009

Actual Primary Completion Date :

Aug 1, 2014

Actual Study Completion Date :

Aug 25, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase 1 Arm A Intermittent OSI-906 Once Daily (QD) on Days 1 - 3, 8 - 10, and 15 - 17 with paclitaxel on Days 1, 8, and 15 (except Treatment Period 1 (TP 1); in TP 1 OSI-906 on Days 1 - 3, 8 - 10, 15 - 17, and 22 - 24 with paclitaxel on Days 8, 15, and 22)	Drug: OSI-906 Administered orally Drug: Paclitaxel Administered intravenously
Experimental: Phase 1 Arm B1 Continuous OSI-906 Twice Daily (BID) (Days 1 - 21) with paclitaxel dosing on Days 1, 8, and 15;(except TP 1; in TP 1 OSI-906 on Days 1 - 3, 8 - 10, 15 - 17, and 22 - 24 with paclitaxel on Days 8, 15 and 22)	Drug: OSI-906 Administered orally Drug: Paclitaxel Administered intravenously
Experimental: Phase 1 Arm B2 Continuous OSI-906 BID (Days 1 - 21) with paclitaxel dosing on Days 1, 8, and 15 (except TP 1; in TP 1 OSI-906 on Days 1 - 3, 8 - 10, 5 - 17, and 22 - 24 with paclitaxel on Days 8, 15, and 22); (additional PK sampling on Days 9 or 13 0r 14 for TP 1)	Drug: OSI-906 Administered orally Drug: Paclitaxel Administered intravenously
Experimental: Phase 1 Arm B3 Continuous OSI-906 BID (Days 1 - 21) with paclitaxel dosing on Days 1, 8, and 15 with no separation in OSI-906 and paclitaxel dosing (except TP 1; in TP 1 continuous OSI-906 dosing 2 hours prior to the initiation of paclitaxel infusion on Day 8 only, with paclitaxel on Days 8, 15, and 22, and additional PK sampling on Day 9 or 13 or 14)	Drug: OSI-906 Administered orally Drug: Paclitaxel Administered intravenously
Experimental: Phase 2 Arm A Intermittent OSI-906 QD on Days 1 - 3, 8 - 10, and 15 - 17 with paclitaxel on Days 1, 8, and 15	Drug: OSI-906 Administered orally Drug: Paclitaxel Administered intravenously
Experimental: Phase 2 Arm B Continuous OSI-906 BID from Day 1 onwards with paclitaxel on Days 1, 8, and 15	Drug: OSI-906 Administered orally Drug: Paclitaxel Administered intravenously
Experimental: Phase 2 Arm C Paclitaxel on Days 1, 8, and 15	Drug: Paclitaxel Administered intravenously
Experimental: Phase 2 Arm C Roll-over Continuous OSI-906 BID from Day 1 onwards	Drug: OSI-906 Administered orally

Outcome Measures

Primary Outcome Measures

Determine Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) [28 days]
Primary outcome measure for Phase 1 portion
Progression Free Survival (PFS) [36 months]
Primary outcome measure for the Phase 2 portion; The time from the date of randomization until date of radiographic disease progression per RECIST v1.1 or until death due to any cause

Secondary Outcome Measures

Objective Response Rate (ORR) [36 months]
The proportion of patients with a confirmed response of Complete Response (CR) or Partial Response (PR) per RECEIST v1.1
Cancer Antigen 125 (CA125) Response Rate [36 months]
Response Rate is defined as at least 50% reduction in serum CA-125 levels from pretreatment levels; Response rate is the proportion of patients with a CA-125 response among evaluable patients
Duration of Response (DOR) [36 months]
The time from the date of the first documented radiographic response (CR/PR) to first documented radiographic progression or death due to underlying cancer
Duration of CA-125 Response (CA-125 DOR) [36 months]
The time from the date of the first documented CA-125 response to the date of CA-125 progression
Overall Survival (OS) [36 months]
The time from the date of randomization until the documented date of death
Safety assessed via physician exam, vital signs, clinical laboratory tests, electrocardiograms (ECG), and adverse events [36 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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
For the phase 2 portion, patients must have elevated CA125 levels evaluable/assessable according to Gynecological Cancer Intergroup (GCIG) criteria (ie, > 70 U/mL) documented by 2 measurements at least 1 week apart
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)
Eastern Cooperative Oncology Group (ECOG) performance status(PS) 0 -1
Predicted life expectancy ≥ 12 weeks
Patients may have had prior therapy, providing the following conditions are met:
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

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 taxanes at some point. Any prior taxanes 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 computerized tomography (CT) scan progressive disease (PD) during chemotherapy) or resistant (radiologically confirmed by CT scan PD within six months of completing chemotherapy) to their last platinum-containing chemotherapy regimen

Radiation: Patients may have had prior radiation therapy provided they have recovered from the acute, toxic effects of radiotherapy prior to registration/randomization. Radiated lesions cannot be chosen as the target lesions

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

Surgery: Previous surgery is permitted provided that adequate wound healing has occurred prior to registration/randomization
Fasting glucose ≤ 150 mg/dL (8.3 mmol/L)
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 Upper Limit of Normal (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
Female patient must be either:
Of non childbearing 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 (one of which must be a barrier method) starting at Screening and throughout the study period and for 28 days [or 5 half lives, whichever is longer] after final study drug administration

Female patient must not be breastfeeding at Screening or during the study period and for 28 days [or 5 half lives of the study drug whichever is longer] after final study drug administration
Female patient must not donate ova starting at Screening and throughout the study period and for 28 days [or 5 half lives of the study drug whichever is longer] after final study drug administration
Patients must provide verbal and written informed consent to participate in the study

Exclusion Criteria:

Diabetes mellitus currently requiring medication (eg, insulin or oral hypoglycemics)
During the phase 2 portion, patients with histology of abdominal adenocarcinoma of unknown origin or a diagnosis of a borderline ovarian tumor
Previous or concurrent malignancies (excluding curatively treated basal or squamous cell carcinoma of the skin or cervical carcinoma in situ) unless the patient has been in remission for at least 3 years
History of significant cardiovascular disease unless the disease is well-controlled. Significant cardiac diseases includes second/third degree heart block; significant ischemic heart disease; 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)
History of cerebrovascular accident (CVA) within 6 months prior to registration/randomization or that is not stable
Prior therapy with an insulin-like growth factor (IGF-1R) inhibitor
Use of drugs that have a risk of causing QT interval prolongation within 14 days prior to Day 1 dosing
Known or prior hypersensitivity to taxanes in spite of premedication or drugs containing Cremophor
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
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
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
Pregnancy or breast-feeding
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
History of allergic reactions attributed to compounds of similar chemical or biologic composition to the study drug
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
Use of drugs that have a known risk of causing Torsade de Pointes (TdP) or that that have a risk of causing QT interval prolongation within 14 days prior to Day 1 dosing are prohibited
Use of the potent CYP1A2 inhibitors ciprofloxacin and fluvoxamine. Other less potent CYP1A2 inhibitors/inducers are not excluded
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Scottsdale	Arizona	United States	85259
2	Department of Obstetrics and Gynecology, University of California, Irvine	Orange	California	United States	92868
3	Horizon Oncology Center	Lafayette	Indiana	United States	47906
4	Ochsner Clinic Foundation	New Orleans	Louisiana	United States	70121
5	Morristown Memorial Hospital	Morristown	New Jersey	United States	07960
6	Blumenthal Cancer Center - Main	Charlotte	North Carolina	United States	28204
7	Duke University Medical Center	Durham	North Carolina	United States	27710
8	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
9	WestMead Hospital	WestMead	New South Wales	Australia	2145
10	Mater Adult Hospital	South Brisbane	Queensland	Australia	4101
11	Royal Adelaide Hospital	North Terrace	South Australia	Australia	5000
12	Launceston General Hospital	Launceston	Tasmania	Australia	7250
13	Frankston Hospital	Frankston	Victoria	Australia	3199
14	Border Medical Oncology	Wodonga	Victoria	Australia	3690
15	St. John of God Hospital, Bunbury	Bunbury	Western Australia	Australia	6230
16	Sir Charles Gairdner Hospital	Perth	Western Australia	Australia	6009
17	St. John of Gog Hospital, Subiaco	Subiaco	Western Australia	Australia	6008
18	Juravinski Cancer Center	Hamilton	Ontario	Canada	L8V 5C2
19	Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
20	McGill University	Montreal	Quebec	Canada	H3T 1E2
21	University Hospital Hradec Kralove	Kralove		Czechia	50005
22	University Hospital Ostrava	Ostrava- Poruba		Czechia	70852
23	General University Hospital, Department of Obstetrics and Gynecology	Prague		Czechia	212000
24	Universitaria di Bologna Policlinico	Bologna		Italy	40138
25	Ospedale di Carpi, AUSL di Modena	Carpi		Italy	91012
26	Instituto Europeo di Oncologia	Milan		Italy	20141
27	Oncology IDI- IRCSS	Roma		Italy	67100
28	III Oddzial Onkologii Ginekologicznej	Lublin		Poland	20-090
29	Oddzial Radioterapii	Poznan		Poland	61 866
30	Klinika Onkologii AM w Poznaniu	Poznan		Poland	61-878
31	Institutul Oncologic Prof. Dr. Ion. Chiricuta Sectia de Oncologie Medicala	Cluj Napoca		Romania	400015
32	Institutul Oncologic Prof. Dr. Ion. Chiricuta Sectia Radiologie	Cluj Napoca		Romania	400015
33	Oncology Medical Centre SCM	Iasi		Romania	700106
34	Clinical Caunty Hospital Mures	Mures		Romania	540072
35	Central Clinical Hospital	Moscow		Russian Federation	129128
36	Moscow City Oncology Hospital	Moscow		Russian Federation	143423
37	State Institution Medical Radiology Scientific Center	Obninsk		Russian Federation	249036
38	Sity Clinical Oncology	St. Petersburg		Russian Federation	198255
39	Ospedale San Giovanni	Bellinzona		Switzerland	CH-6500
40	Drug Development Unit Royal Mardsen NHS Foundation Trust	Sutton	Surrey	United Kingdom	SM2 5PT
41	Royal Marsden Hospital	London		United Kingdom	SW3 6JJ
42	University College Hospital	London		United Kingdom	WC1E 6BT
43	The Christie NHS Foundation Trust	Manchester		United Kingdom	M20 4BX
44	Mount Vernon Cancer Center	Northwood		United Kingdom	HA62RN
45	Churchill Hospital	Oxford		United Kingdom	OX37LI
46	Christie NHS Foundation Trust	Withington		United Kingdom	M20 4BX

Sponsors and Collaborators

Astellas Pharma Inc

Investigators

Principal Investigator: Principal Investigator - Czech Republic, General Faculty Hospital, Charles University
Study Director: Medical Director, Astellas Pharma Global Development
Principal Investigator: Principal Investigator - Italy, Instituto Europeo de Oncologia