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

NCT ID: NCT00889382

Last Updated: 2024-11-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 152 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-08-05
• Study Completion Date: 2014-08-25

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.

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.

Conditions

Ovarian Cancer; Solid Tumors

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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)

Group Type: EXPERIMENTAL

OSI-906

Intervention Type: DRUG

Administered orally

Paclitaxel

Intervention Type: DRUG

Administered intravenously

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)

Group Type: EXPERIMENTAL

OSI-906

Intervention Type: DRUG

Administered orally

Paclitaxel

Intervention Type: DRUG

Administered intravenously

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)

Group Type: EXPERIMENTAL

OSI-906

Intervention Type: DRUG

Administered orally

Paclitaxel

Intervention Type: DRUG

Administered intravenously

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)

Group Type: EXPERIMENTAL

OSI-906

Intervention Type: DRUG

Administered orally

Paclitaxel

Intervention Type: DRUG

Administered intravenously

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

Group Type: EXPERIMENTAL

OSI-906

Intervention Type: DRUG

Administered orally

Paclitaxel

Intervention Type: DRUG

Administered intravenously

Phase 2 Arm B

Continuous OSI-906 BID from Day 1 onwards with paclitaxel on Days 1, 8, and 15

Group Type: EXPERIMENTAL

OSI-906

Intervention Type: DRUG

Administered orally

Paclitaxel

Intervention Type: DRUG

Administered intravenously

Phase 2 Arm C

Paclitaxel on Days 1, 8, and 15

Group Type: EXPERIMENTAL

Paclitaxel

Intervention Type: DRUG

Administered intravenously

Phase 2 Arm C Roll-over

Continuous OSI-906 BID from Day 1 onwards

Group Type: EXPERIMENTAL

OSI-906

Intervention Type: DRUG

Administered orally

Interventions

OSI-906

Administered orally

Intervention Type: DRUG

Paclitaxel

Administered intravenously

Intervention Type: DRUG

Eligibility Criteria

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

1. Patient should have recovered from any drug-related toxicities (with the exception of grade 1 neuropathy and or alopecia)

2. 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

3. 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. 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:

1. post-menopausal (defined as at least 1 year without any menses) prior to Screening, or

2. documented surgically sterile or status post hysterectomy (at least 1 month prior to Screening)

• Or, if of childbearing potential:

1. must have a negative urine pregnancy test at Screening, and

2. 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Astellas Pharma Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Principal Investigator - Czech Republic

Role: PRINCIPAL_INVESTIGATOR

General Faculty Hospital, Charles University

Medical Director

Role: STUDY_DIRECTOR

Astellas Pharma Global Development

Principal Investigator - Italy

Role: PRINCIPAL_INVESTIGATOR

Instituto Europeo de Oncologia

Locations

Mayo Clinic

Scottsdale, Arizona, United States

Department of Obstetrics and Gynecology, University of California, Irvine

Orange, California, United States

Horizon Oncology Center

Lafayette, Indiana, United States

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

Morristown Memorial Hospital

Morristown, New Jersey, United States

Blumenthal Cancer Center - Main

Charlotte, North Carolina, United States

Duke University Medical Center

Durham, North Carolina, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

WestMead Hospital

Westmead, New South Wales, Australia

Mater Adult Hospital

South Brisbane, Queensland, Australia

Royal Adelaide Hospital

North Terrace, South Australia, Australia

Launceston General Hospital

Launceston, Tasmania, Australia

Frankston Hospital

Frankston, Victoria, Australia

Border Medical Oncology

Wodonga, Victoria, Australia

St. John of God Hospital, Bunbury

Bunbury, Western Australia, Australia

Sir Charles Gairdner Hospital

Perth, Western Australia, Australia

St. John of Gog Hospital, Subiaco

Subiaco, Western Australia, Australia

Juravinski Cancer Center

Hamilton, Ontario, Canada

Princess Margaret Hospital

Toronto, Ontario, Canada

McGill University

Montreal, Quebec, Canada

University Hospital Hradec Kralove

Kralove, , Czechia

University Hospital Ostrava

Ostrava- Poruba, , Czechia

General University Hospital, Department of Obstetrics and Gynecology

Prague, , Czechia

Universitaria di Bologna Policlinico

Bologna, , Italy

Ospedale di Carpi, AUSL di Modena

Carpi, , Italy

Instituto Europeo di Oncologia

Milan, , Italy

Oncology IDI- IRCSS

Roma, , Italy

III Oddzial Onkologii Ginekologicznej

Lublin, , Poland

Oddzial Radioterapii

Poznan, , Poland

Klinika Onkologii AM w Poznaniu

Poznan, , Poland

Institutul Oncologic Prof. Dr. Ion. Chiricuta Sectia de Oncologie Medicala

Cluj-Napoca, , Romania

Institutul Oncologic Prof. Dr. Ion. Chiricuta Sectia Radiologie

Cluj-Napoca, , Romania

Oncology Medical Centre SCM

Iași, , Romania

Clinical Caunty Hospital Mures

Mures, , Romania

Central Clinical Hospital

Moscow, , Russia

Moscow City Oncology Hospital

Moscow, , Russia

State Institution Medical Radiology Scientific Center

Obninsk, , Russia

Sity Clinical Oncology

Saint Petersburg, , Russia

Ospedale San Giovanni

Bellinzona, , Switzerland

Drug Development Unit Royal Mardsen NHS Foundation Trust

Sutton, Surrey, United Kingdom

Royal Marsden Hospital

London, , United Kingdom

University College Hospital

London, , United Kingdom

The Christie NHS Foundation Trust

Manchester, , United Kingdom

Mount Vernon Cancer Center

Northwood, , United Kingdom

Churchill Hospital

Oxford, , United Kingdom

Christie NHS Foundation Trust

Withington, , United Kingdom

Countries

United States; Australia; Canada; Czechia; Italy; Poland; Romania; Russia; Switzerland; United Kingdom

Related Links

https://astellasclinicalstudyresults.com/hcp/study.aspx?ID=270

Link to results on Astellas Clinical Study Results website

Other Identifiers

2009-010319-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

OSI-906-202

Identifier Type: -

Identifier Source: org_study_id