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Safety and Tolerability Study of ISIS EIF4E Rx in Combination With Carboplatin and Paclitaxel (NSCLC)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Isis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01234038
First received: November 2, 2010
Last updated: November 1, 2012
Last verified: November 2012
  Purpose

The purpose of this study is to examine the overall survival of patients with Stage IV non-small cell lung cancer (NSCLC) treated with ISIS EIF4E Rx in combination with carboplatin and paclitaxel.


Condition Intervention Phase
Non-small Cell Lung Cancer
Drug: ISIS EIF4E Rx
Drug: Paclitaxel
Drug: Carboplatin
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 1b/2 Study of Carboplatin-Paclitaxel, With or Without ISIS 183750 (an eIF4E Inhibitor), in Patients With Stage IV Non-Small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by Isis Pharmaceuticals:

Primary Outcome Measures:
  • Progression free survival [ Time Frame: At the end of each 21 day cycle ] [ Designated as safety issue: No ]

Estimated Enrollment: 112
Study Start Date: November 2010
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1 Cohort 1 Drug: ISIS EIF4E Rx
800 mg ISIS EIF4E Rx administered as a 3-hour intravenous infusion on Days 1, 8 and 15 of each 21 day cycle
Drug: Paclitaxel
200 mg/m2 administered as a 3-hour intravenous infusion on Day 1 of each 21 day cycle
Drug: Carboplatin
AUC 6.0 mg/mL/min administered as a 1-hour intravenous infusion on Day 1 of each 21 day cycle
Experimental: Part 1 Cohort 2 Drug: ISIS EIF4E Rx
1000 mg ISIS EIF4E Rx administered as a 3-hour intravenous infusion on Days 1, 8 and 15 of each 21 day cycle
Drug: Paclitaxel
200 mg/m2 administered as a 3-hour intravenous infusion on Day 1 of each 21 day cycle
Drug: Carboplatin
AUC 6.0 mg/mL/min administered as a 1-hour intravenous infusion on Day 1 of each 21 day cycle
Experimental: Part 2 Arm A Drug: Paclitaxel
200 mg/m2 administered as a 3-hour intravenous infusion on Day 1 of each 21 day cycle
Drug: Carboplatin
AUC 6.0 mg/mL/min administered as a 1-hour intravenous infusion on Day 1 of each 21 day cycle
Experimental: Part 2 Arm B Drug: ISIS EIF4E Rx
(Dose identified in Part 1)ISIS EIF4E Rx administered as a 3-hour intravenous infusion on Days 1, 8, and 15 of each 21 day cycle
Drug: Paclitaxel
200 mg/m2 administered as a 3-hour intravenous infusion on Day 1 of each 21 day cycle
Drug: Carboplatin
AUC 6.0 mg/mL/min administered as a 1-hour intravenous infusion on Day 1 of each 21 day cycle

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female patients age >/= 18 years
  • Histologically or cytologically confirmed diagnosis of NSCLC
  • Stage IV disease (including patients with pleural effusion who were previously classified as Stage IIIB)
  • All of the following if patient has had prior radiation therapy:

    1. Lesion(s) used for determination of response were not previously irradiated or have increased in size since the completion of radiotherapy
    2. The patient has recovered from any acute effects of the radiotherapy
    3. Radiotherapy was completed at least 4 weeks prior to Screening
  • Part 1: Have at least non-measurable evaluable disease (e.g., lesions which are smaller than the minimum size required for measurability; other non-measurable lesions such as bone metastases, malignant pleural effusion)
  • Part 2: Have measurable disease, defined as at least 1 lesion that can be accurately measured in at least 1 dimension
  • Performance status of 0 or 1 on the ECOG Performance Status Scale
  • Have an estimated life expectancy of at least 12 weeks
  • Adequate organ function within 14 days prior to first study dose (ISIS EIF4E Rx or carboplatin/paclitaxel, whichever occurs first) as defined by:

    1. Absolute neutrophil count (ANC) >/= 1.5 x 109/L
    2. Platelet count >/= 100 x 109/L
    3. Hemoglobin >/=9 g/dL (>/= 5.6 mmol/L). Patients may receive packed RBC transfusion to achieve this level at the discretion of the investigator.
    4. Total bilirubin < 1.5 x upper limit of normal (ULN) unless elevated secondary to conditions such as Gilbert's Disease
    5. Aspartate aminotransferase (AST) < 3 x ULN (< 5 x ULN in the presence of hepatic metastases)
    6. Alanine aminotransferase (ALT) < 3 x ULN (< 5 x ULN in the presence of hepatic metastases)
    7. Alkaline phosphatase < 3.0 x ULN
    8. Calculated creatinine clearance >/= 60 mL/min per Cockcroft and Gault formula
  • Satisfy one of the following:

    1. Females: non-pregnant and non-lactating; surgically sterile, post-menopausal, or patient or partner compliant with a reliable contraceptive regimen, as determined by Investigator, for 4 weeks prior to Screening. Patients of reproductive potential must test negative for pregnancy at Screen and must agree to use a reliable method of birth control during the study and for the 10 weeks following the last dose of ISIS EIF4E Rx.
    2. Males: surgically sterile or patient or partner must agree to use a reliable contraceptive method, as determined by the Investigator during the study and for the 10 weeks following the last dose of ISIS EIF4E Rx.
  • For Part 1: have discontinued all prior chemotherapies, biological therapies, and other investigational therapies for cancer for at least 4 weeks (6 weeks for mitomycin-C or nitrosoureas) prior to study treatment and recovered from the acute effects of therapy.

Exclusion Criteria:

  • Part 1: More than 2 prior chemotherapy or biological therapy regimens (approved or experimental) for NSCLC, not counting adjuvant and neoadjuvant treatment. A regimen is defined as two or more consecutive cycles of treatment.
  • Part 2: Any prior chemotherapy or biological therapy (approved or experimental) for NSCLC including adjuvant and neoadjuvant treatments
  • Treatment with another investigational drug, biological agent, or device within 4 weeks (6 weeks for biological agents) before Screening or 5 half-lives of study agent, whichever is longer
  • Patients with treated or untreated parenchymal brain metastases or leptomeningeal disease. Brain imaging is required for symptomatic patients to rule out brain metastases, but is not required in asymptomatic patients.
  • Patients with known pericardial effusion
  • Have active infection or serious concomitant systemic disorder (for example, heart failure) incompatible with the study (at the discretion of the Investigator)
  • Presence or history of malignancy other than NSCLC, carcinoma in situ of the cervix, or non-melanoma skin cancer. In the case of other malignancies, patients may be considered for participation if the prior malignancies were diagnosed and definitively treated at least five years previously with no subsequent evidence of recurrence.
  • Presence of an underlying disease state associated with active bleeding
  • Ongoing therapy with oral or parenteral anticoagulants (e.g., heparin, warfarin/coumadin). Low-dose anticoagulants for maintenance of catheter patency and low dose aspirin (≤ 325 mg/day) and nonsteroidal anti-inflammatory agents are not exclusionary.
  • Concurrent treatment with other anticancer drugs
  • Pre-existing peripheral neuropathy >/=Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE) Grade 2
  • Known history of HIV, HCV, or chronic HBV infection
  • Previous treatment with a therapeutic antisense oligonucleotide or siRNA
  • Planned concomitant participation in another clinical trial of an experimental agent, vaccine, or device
  • Have any other medical conditions that in the opinion of the Investigator, would make the patient unsuitable for enrollment, or could interfere with the patient participating in or completing the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01234038

Locations
United States, Alabama
Achieve Clinical Research
Birmingham, Alabama, United States, 35216
United States, Arkansas
Highlands Oncology Group
Fayetteville, Arkansas, United States, 72703
Genesis Cancer Center
Hot Springs, Arkansas, United States, 71913
Little Rock Cancer Clinic
Little Rock, Arkansas, United States, 72205
United States, Kentucky
University of Louisville - James Graham Brown Cancer Center
Louisville, Kentucky, United States, 40202
United States, Ohio
Gabrail Cancer Center
Canton, Ohio, United States, 44718
Hungary
Koranyi National Institute of TBC and Pulmonology
Budapest, Hungary, H-1121
Semmelweis University Faculty of Medicine
Budapest, Hungary, H-1125
University of Debrecen, Medical and Health Science Center
Debrecen, Hungary, H-4032
Hospital for Thoracic Diseases of Csongrad County Local Governmental
Deszk, Hungary, H-6772
Bekes Country Pandy Kalman Hospital
Gyula, Hungary, H-5703
Poland
K. Dluski Provincial Specialist Hospital
Bialystok, Poland, 15-540
Independent Public Teaching Hospital No. 4 In Lublin
Lublin, Poland, 20-954
Idependent Public Tuberculosis an Lung Diseases Facilities
Olsztyn, Poland, 10-357
Specialist Tuberculosis and Lung Diseases Hospitals
Rzeszow, Poland, 35-241
Alojzy Pawelec Provincial Hospital of Lung Diseases
Wodzislaw Slaski, Poland, 44-300
Russian Federation
State Medical Institution: Arkhangelsk Regional Clinical Oncology Center, Chemotherapy department
Arkhangelsk, Russian Federation, 163045
State Therapeutical and Prophylactic Institution: Chelyabinsk Regional Clinical Oncology Center, Chemotherapy Department
Chelyabinsk, Russian Federation, 454087
State Budget Healthcare Institution: Sverdlovsk Regional Oncology Center, Radiotherapy Department
Ekaterinburg, Russian Federation, 620036
State Healthcare Institution: Ivanovo Regional Oncology Center, Chemotherapy Department
Ivanovo, Russian Federation, 153013
Non-State Medical Institution: Central Clinical Hospital #2 n.a. N.A. Semashko under OJSC Russian Railways, Chemotherapy Dept.
Moscow, Russian Federation, 129128
St. Petersburg State Healthcare Institution: "City Clinical Oncology Center"
Saint Petersburg, Russian Federation, 197022
State Healthcare Institution: Leningrad Regional Clinical Hospital, Thoracic Surgery Department
Saint Petersburg, Russian Federation, 194291
State Higher Educational Institution: St. Petersburg State Medica University n.a.I.P. Pavlov under the Federal Agency for Healthcare and Social Development, Pulmonology Research Institute
Saint Petersburg, Russian Federation, 197101
State Institution: Samara Regional Clinical Oncology Center, Chemotherapy Department
Samara, Russian Federation, 443031
Sponsors and Collaborators
Isis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Isis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01234038     History of Changes
Other Study ID Numbers: ISIS 183750-CS4
Study First Received: November 2, 2010
Last Updated: November 1, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Isis Pharmaceuticals:
Non-small cell lung cancer

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Carboplatin
Paclitaxel
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on November 20, 2014