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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc
ClinicalTrials.gov Identifier:
NCT00889382
First received: April 6, 2009
Last updated: February 6, 2014
Last verified: February 2014
  Purpose

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 Intervention Phase
Solid Tumors
Ovarian Cancer
Drug: OSI-906
Drug: Paclitaxel
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Determine Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    Primary outcome measure for Phase 1 portion

  • Progression Free Survival (PFS) [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    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) [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    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) [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    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) [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    The time from the date of the first documented CA-125 response to the date of CA-125 progression

  • Overall Survival (OS) [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 36 months ] [ Designated as safety issue: No ]

Enrollment: 152
Study Start Date: July 2009
Study Completion Date: January 2014
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00889382

  Show 46 Study Locations
Sponsors and Collaborators
Astellas Pharma Inc
Investigators
Study Director: Medical Director Astellas Pharma Global Development
Principal Investigator: Principal Investigator - Italy Instituto Europeo de Oncologia
Principal Investigator: Principal Investigator - Czech Republic General Faculty Hospital, Charles University
  More Information

No publications provided

Responsible Party: Astellas Pharma Inc
ClinicalTrials.gov Identifier: NCT00889382     History of Changes
Other Study ID Numbers: OSI-906-202, 2009-010319-34
Study First Received: April 6, 2009
Last Updated: February 6, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Czech Republic: State Institute for Drug Control
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Poland: Ministry of Health
Romania: Ministry of Public Health
Russia: Ministry of Health of the Russian Federation
Switzerland: Swissmedic
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Astellas Pharma Inc:
Ovarian Cancer
Ovarian
Paclitaxel
OSI-906
IGF-1R
Solid Tumors

Additional relevant MeSH terms:
Ovarian Neoplasms
Neoplasms
Neoplasms, Glandular and Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Neoplasms by Histologic Type
Paclitaxel
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 22, 2014