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

Ovarian Cancer Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00889382
• Other study ID #: OSI-906-202
• Secondary ID: 2009-010319-34
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: August 5, 2009
• Est. completion date: August 25, 2014

Study information

• Verified date: November 2019
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 152
• Est. completion date: August 25, 2014
• Est. primary completion date: August 1, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Ovarian Cancer
• Ovarian Neoplasms
• Solid Tumors

Intervention

Drug:
• OSI-906
Administered orally
• Paclitaxel
Administered intravenously

Locations

Country	Name	City	State
Australia	St. John of God Hospital, Bunbury	Bunbury	Western Australia
Australia	Frankston Hospital	Frankston	Victoria
Australia	Launceston General Hospital	Launceston	Tasmania
Australia	Royal Adelaide Hospital	North Terrace	South Australia
Australia	Sir Charles Gairdner Hospital	Perth	Western Australia
Australia	Mater Adult Hospital	South Brisbane	Queensland
Australia	St. John of Gog Hospital, Subiaco	Subiaco	Western Australia
Australia	WestMead Hospital	WestMead	New South Wales
Australia	Border Medical Oncology	Wodonga	Victoria
Canada	Juravinski Cancer Center	Hamilton	Ontario
Canada	McGill University	Montreal	Quebec
Canada	Princess Margaret Hospital	Toronto	Ontario
Czechia	University Hospital Hradec Kralove	Kralove
Czechia	University Hospital Ostrava	Ostrava- Poruba
Czechia	General University Hospital, Department of Obstetrics and Gynecology	Prague
Italy	Universitaria di Bologna Policlinico	Bologna
Italy	Ospedale di Carpi, AUSL di Modena	Carpi
Italy	Instituto Europeo di Oncologia	Milan
Italy	Oncology IDI- IRCSS	Roma
Poland	III Oddzial Onkologii Ginekologicznej	Lublin
Poland	Klinika Onkologii AM w Poznaniu	Poznan
Poland	Oddzial Radioterapii	Poznan
Romania	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	Iasi
Romania	Clinical Caunty Hospital Mures	Mures
Russian Federation	Central Clinical Hospital	Moscow
Russian Federation	Moscow City Oncology Hospital	Moscow
Russian Federation	State Institution Medical Radiology Scientific Center	Obninsk
Russian Federation	Sity Clinical Oncology	St. Petersburg
Switzerland	Ospedale San Giovanni	Bellinzona
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	Drug Development Unit Royal Mardsen NHS Foundation Trust	Sutton	Surrey
United Kingdom	Christie NHS Foundation Trust	Withington
United States	Blumenthal Cancer Center - Main	Charlotte	North Carolina
United States	Duke University Medical Center	Durham	North Carolina
United States	Horizon Oncology Center	Lafayette	Indiana
United States	Morristown Memorial Hospital	Morristown	New Jersey
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Department of Obstetrics and Gynecology, University of California, Irvine	Orange	California
United States	Mayo Clinic	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma Inc

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Czechia,  Italy,  Poland,  Romania,  Russian Federation,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)	Primary outcome measure for Phase 1 portion	28 days
Primary	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	Objective Response Rate (ORR)	The proportion of patients with a confirmed response of Complete Response (CR) or Partial Response (PR) per RECEIST v1.1	36 months
Secondary	Cancer Antigen 125 (CA125) Response Rate	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	36 months
Secondary	Duration of Response (DOR)	The time from the date of the first documented radiographic response (CR/PR) to first documented radiographic progression or death due to underlying cancer	36 months
Secondary	Duration of CA-125 Response (CA-125 DOR)	The time from the date of the first documented CA-125 response to the date of CA-125 progression	36 months
Secondary	Overall Survival (OS)	The time from the date of randomization until the documented date of death	36 months
Secondary	Safety assessed via physician exam, vital signs, clinical laboratory tests, electrocardiograms (ECG), and adverse events		36 months

External Links

•   Link to results on Astellas Clinical Study Results website