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

NCT00889382 | Completed Phase 1 FDA Drug

• 2 other identifiers: OSI-906-2022009-010319-34
• Study Type: interventional
• Target: 152
• Locations: 10 countries
• Sites: 46

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.

Conditions

Ovarian Cancer; Solid Tumors

Keywords

Ovarian; IGF-1R; Paclitaxel; Ovarian Cancer; OSI-906; Solid Tumors

Outcome Measures

Primary Outcomes (2)

• Determine Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)

  Primary outcome measure for Phase 1 portion

  28 days

• Progression Free Survival (PFS)

  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

  36 months

Secondary Outcomes (6)

• Objective Response Rate (ORR)

  36 months

• Cancer Antigen 125 (CA125) Response Rate

  36 months

• Duration of Response (DOR)

  36 months

• Duration of CA-125 Response (CA-125 DOR)

  36 months

• Overall Survival (OS)

  36 months

Study Arms (8)

Phase 1 Arm A

EXPERIMENTAL

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; Drug: Paclitaxel

Phase 1 Arm B1

EXPERIMENTAL

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; Drug: Paclitaxel

Phase 1 Arm B2

EXPERIMENTAL

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; Drug: Paclitaxel

Phase 1 Arm B3

EXPERIMENTAL

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; Drug: Paclitaxel

Phase 2 Arm A

EXPERIMENTAL

Intermittent OSI-906 QD on Days 1 - 3, 8 - 10, and 15 - 17 with paclitaxel on Days 1, 8, and 15

Drug: OSI-906; Drug: Paclitaxel

Phase 2 Arm B

EXPERIMENTAL

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

Drug: OSI-906; Drug: Paclitaxel

Phase 2 Arm C

EXPERIMENTAL

Paclitaxel on Days 1, 8, and 15

Drug: Paclitaxel

Phase 2 Arm C Roll-over

EXPERIMENTAL

Continuous OSI-906 BID from Day 1 onwards

Drug: OSI-906

Interventions

OSI-906 DRUG

Administered orally

Phase 1 Arm A; Phase 1 Arm B1; Phase 1 Arm B2; Phase 1 Arm B3; Phase 2 Arm A; Phase 2 Arm B; Phase 2 Arm C Roll-over

Paclitaxel DRUG

Administered intravenously

Phase 1 Arm A; Phase 1 Arm B1; Phase 1 Arm B2; Phase 1 Arm B3; Phase 2 Arm A; Phase 2 Arm B; Phase 2 Arm C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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. 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Astellas Pharma Inc: lead

Study Sites (46)

Mayo Clinic

Scottsdale, Arizona, 85259, United States

Location

Department of Obstetrics and Gynecology, University of California, Irvine

Orange, California, 92868, United States

Location

Horizon Oncology Center

Lafayette, Indiana, 47906, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

Morristown Memorial Hospital

Morristown, New Jersey, 07960, United States

Location

Blumenthal Cancer Center - Main

Charlotte, North Carolina, 28204, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

WestMead Hospital

Westmead, New South Wales, 2145, Australia

Location

Mater Adult Hospital

South Brisbane, Queensland, 4101, Australia

Location

Royal Adelaide Hospital

North Terrace, South Australia, 5000, Australia

Location

Launceston General Hospital

Launceston, Tasmania, 7250, Australia

Location

Frankston Hospital

Frankston, Victoria, 3199, Australia

Location

Border Medical Oncology

Wodonga, Victoria, 3690, Australia

Location

St. John of God Hospital, Bunbury

Bunbury, Western Australia, 6230, Australia

Location

Sir Charles Gairdner Hospital

Perth, Western Australia, 6009, Australia

Location

St. John of Gog Hospital, Subiaco

Subiaco, Western Australia, 6008, Australia

Location

Juravinski Cancer Center

Hamilton, Ontario, L8V 5C2, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

McGill University

Montreal, Quebec, H3T 1E2, Canada

Location

University Hospital Hradec Kralove

Kralove, 50005, Czechia

Location

University Hospital Ostrava

Ostrava- Poruba, 70852, Czechia

Location

General University Hospital, Department of Obstetrics and Gynecology

Prague, 212000, Czechia

Location

Universitaria di Bologna Policlinico

Bologna, 40138, Italy

Location

Ospedale di Carpi, AUSL di Modena

Carpi, 91012, Italy

Location

Instituto Europeo di Oncologia

Milan, 20141, Italy

Location

Oncology IDI- IRCSS

Roma, 67100, Italy

Location

III Oddzial Onkologii Ginekologicznej

Lublin, 20-090, Poland

Location

Oddzial Radioterapii

Poznan, 61 866, Poland

Location

Klinika Onkologii AM w Poznaniu

Poznan, 61-878, Poland

Location

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

Cluj-Napoca, 400015, Romania

Location

Institutul Oncologic Prof. Dr. Ion. Chiricuta Sectia Radiologie

Cluj-Napoca, 400015, Romania

Location

Oncology Medical Centre SCM

Iași, 700106, Romania

Location

Clinical Caunty Hospital Mures

Mures, 540072, Romania

Location

Central Clinical Hospital

Moscow, 129128, Russia

Location

Moscow City Oncology Hospital

Moscow, 143423, Russia

Location

State Institution Medical Radiology Scientific Center

Obninsk, 249036, Russia

Location

Sity Clinical Oncology

Saint Petersburg, 198255, Russia

Location

Ospedale San Giovanni

Bellinzona, CH-6500, Switzerland

Location

Drug Development Unit Royal Mardsen NHS Foundation Trust

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Royal Marsden Hospital

London, SW3 6JJ, United Kingdom

Location

University College Hospital

London, WC1E 6BT, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Mount Vernon Cancer Center

Northwood, HA62RN, United Kingdom

Location

Churchill Hospital

Oxford, OX37LI, United Kingdom

Location

Christie NHS Foundation Trust

Withington, M20 4BX, United Kingdom

Location

Related Links

• Link to results on Astellas Clinical Study Results website

MeSH Terms

Conditions

Ovarian Neoplasms; Insulin-Like Growth Factor I, Resistance To

Interventions

3-(8-amino-1-(2-phenylquinolin-7-yl)imidazo(1,5-a)pyrazin-3-yl)-1-methylcyclobutanol; Paclitaxel

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Principal Investigator - Czech Republic

  General Faculty Hospital, Charles University

  PRINCIPAL INVESTIGATOR

• Medical Director

  Astellas Pharma Global Development

  STUDY DIRECTOR

• Principal Investigator - Italy

  Instituto Europeo de Oncologia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 6, 2009
• First Posted: April 28, 2009
• Study Start: August 5, 2009
• Primary Completion: August 1, 2014
• Study Completion: August 25, 2014
• Last Updated: November 20, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.

Locations

IT (4); RO (4); CA (3); GB (7); US (8); CZ (3); CH (1); RU (4); PL (3); AU (9)