Clinical trial NCT00889382: A Study Evaluating Intermittent and Continuous OSI-906 and Weekly Paclitaxel in Patients With Recurrent Epithelial Ovarian Cancer (and Other Solid Tumors)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Ovarian Cancer
Solid Tumors
Keywords: Ovarian
IGF-1R
Paclitaxel
Ovarian Cancer
OSI-906
Solid Tumors
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2009-04-28
Enrollment: 152
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Determine Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)
timeFrame: 28 days
measure: Progression Free Survival (PFS)
timeFrame: 36 months
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: 36 months
measure: Cancer Antigen 125 (CA125) Response Rate
timeFrame: 36 months
measure: Duration of Response (DOR)
timeFrame: 36 months
measure: Duration of CA-125 Response (CA-125 DOR)
timeFrame: 36 months
measure: Overall Survival (OS)
timeFrame: 36 months
measure: Safety assessed via physician exam, vital signs, clinical laboratory tests, electrocardiograms (ECG), and adverse events
timeFrame: 36 months
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: Orange
country: United States
facility: Department of Obstetrics and Gynecology, University of California, Irvine
state: California
city: Lafayette
country: United States
facility: Horizon Oncology Center
state: Indiana
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Morristown
country: United States
facility: Morristown Memorial Hospital
state: New Jersey
city: Charlotte
country: United States
facility: Blumenthal Cancer Center - Main
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: WestMead
country: Australia
facility: WestMead Hospital
state: New South Wales
city: South Brisbane
country: Australia
facility: Mater Adult Hospital
state: Queensland
city: North Terrace
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Launceston
country: Australia
facility: Launceston General Hospital
state: Tasmania
city: Frankston
country: Australia
facility: Frankston Hospital
state: Victoria
city: Wodonga
country: Australia
facility: Border Medical Oncology
state: Victoria
city: Bunbury
country: Australia
facility: St. John of God Hospital, Bunbury
state: Western Australia
city: Perth
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Subiaco
country: Australia
facility: St. John of Gog Hospital, Subiaco
state: Western Australia
city: Hamilton
country: Canada
facility: Juravinski Cancer Center
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: McGill University
state: Quebec
city: Kralove
country: Czechia
facility: University Hospital Hradec Kralove
city: Ostrava- Poruba
country: Czechia
facility: University Hospital Ostrava
city: Prague
country: Czechia
facility: General University Hospital, Department of Obstetrics and Gynecology
city: Bologna
country: Italy
facility: Universitaria di Bologna Policlinico
city: Carpi
country: Italy
facility: Ospedale di Carpi, AUSL di Modena
city: Milan
country: Italy
facility: Instituto Europeo di Oncologia
city: Roma
country: Italy
facility: Oncology IDI- IRCSS
city: Lublin
country: Poland
facility: III Oddzial Onkologii Ginekologicznej
city: Poznan
country: Poland
facility: Oddzial Radioterapii
city: Poznan
country: Poland
facility: Klinika Onkologii AM w Poznaniu
city: Cluj Napoca
country: Romania
facility: Institutul Oncologic Prof. Dr. Ion. Chiricuta Sectia de Oncologie Medicala
city: Cluj Napoca
country: Romania
facility: Institutul Oncologic Prof. Dr. Ion. Chiricuta Sectia Radiologie
city: Iasi
country: Romania
facility: Oncology Medical Centre SCM
city: Mures
country: Romania
facility: Clinical Caunty Hospital Mures
city: Moscow
country: Russian Federation
facility: Central Clinical Hospital
city: Moscow
country: Russian Federation
facility: Moscow City Oncology Hospital
city: Obninsk
country: Russian Federation
facility: State Institution Medical Radiology Scientific Center
city: St. Petersburg
country: Russian Federation
facility: Sity Clinical Oncology
city: Bellinzona
country: Switzerland
facility: Ospedale San Giovanni
city: Sutton
country: United Kingdom
facility: Drug Development Unit Royal Mardsen NHS Foundation Trust
state: Surrey
city: London
country: United Kingdom
facility: Royal Marsden Hospital
city: London
country: United Kingdom
facility: University College Hospital
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Northwood
country: United Kingdom
facility: Mount Vernon Cancer Center
city: Oxford
country: United Kingdom
facility: Churchill Hospital
city: Withington
country: United Kingdom
facility: Christie NHS Foundation Trust
Study officials:
affiliation: General Faculty Hospital, Charles University
name: Principal Investigator - Czech Republic
role: PRINCIPAL_INVESTIGATOR
affiliation: Astellas Pharma Global Development
name: Medical Director
role: STUDY_DIRECTOR
affiliation: Instituto Europeo de Oncologia
name: Principal Investigator - Italy
role: PRINCIPAL_INVESTIGATOR
References: