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

NCT01234038 | Completed Phase 1

• 1 other identifier: ISIS 183750-CS4
• Study Type: interventional
• Target: 116
• Locations: 4 countries
• Sites: 29

Brief Summary

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.

Conditions

Non-small Cell Lung Cancer

Keywords

Non-small cell lung cancer

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  At the end of each 21 day cycle

Study Arms (4)

Part 1 Cohort 1

EXPERIMENTAL

Drug: ISIS EIF4E Rx; Drug: Paclitaxel; Drug: Carboplatin

Part 1 Cohort 2

EXPERIMENTAL

Drug: ISIS EIF4E Rx; Drug: Paclitaxel; Drug: Carboplatin

Part 2 Arm A

EXPERIMENTAL

Drug: Paclitaxel; Drug: Carboplatin

Part 2 Arm B

EXPERIMENTAL

Drug: ISIS EIF4E Rx; Drug: Paclitaxel; Drug: Carboplatin

Interventions

ISIS EIF4E Rx DRUG

800 mg ISIS EIF4E Rx administered as a 3-hour intravenous infusion on Days 1, 8 and 15 of each 21 day cycle

Part 1 Cohort 1

Paclitaxel DRUG

200 mg/m2 administered as a 3-hour intravenous infusion on Day 1 of each 21 day cycle

Part 1 Cohort 1; Part 1 Cohort 2; Part 2 Arm A; Part 2 Arm B

Carboplatin DRUG

AUC 6.0 mg/mL/min administered as a 1-hour intravenous infusion on Day 1 of each 21 day cycle

Part 1 Cohort 1; Part 1 Cohort 2; Part 2 Arm A; Part 2 Arm B

Eligibility Criteria

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

You may qualify if:

• 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:
• Lesion(s) used for determination of response were not previously irradiated or have increased in size since the completion of radiotherapy
• The patient has recovered from any acute effects of the radiotherapy
• 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:
• Absolute neutrophil count (ANC) \>/= 1.5 x 109/L
• Platelet count \>/= 100 x 109/L
• Hemoglobin \>/=9 g/dL (\>/= 5.6 mmol/L). Patients may receive packed RBC transfusion to achieve this level at the discretion of the investigator.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Ionis Pharmaceuticals, Inc.: lead

Study Sites (29)

Achieve Clinical Research

Birmingham, Alabama, 35216, United States

Location

Highlands Oncology Group

Fayetteville, Arkansas, 72703, United States

Location

Genesis Cancer Center

Hot Springs, Arkansas, 71913, United States

Location

Little Rock Cancer Clinic

Little Rock, Arkansas, 72205, United States

Location

Kenmar Research Institute

Los Angeles, California, 90057, United States

Location

Joliet Hematology Oncology Associates

Joliet, Illinois, 60435, United States

Location

University of Louisville - James Graham Brown Cancer Center

Louisville, Kentucky, 40202, United States

Location

Jewish Hospital & St. Mary's Healthcare

Louisville, Kentucky, 40245, United States

Location

Gabrail Cancer Center

Canton, Ohio, 44718, United States

Location

Cancer Therapy and Research Center, University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

Koranyi National Institute of TBC and Pulmonology

Budapest, H-1121, Hungary

Location

Semmelweis University Faculty of Medicine

Budapest, H-1125, Hungary

Location

University of Debrecen, Medical and Health Science Center

Debrecen, H-4032, Hungary

Location

Hospital for Thoracic Diseases of Csongrad County Local Governmental

Deszk, H-6772, Hungary

Location

Bekes Country Pandy Kalman Hospital

Gyula, H-5703, Hungary

Location

K. Dluski Provincial Specialist Hospital

Bialystok, 15-540, Poland

Location

Independent Public Teaching Hospital No. 4 In Lublin

Lublin, 20-954, Poland

Location

Idependent Public Tuberculosis an Lung Diseases Facilities

Olsztyn, 10-357, Poland

Location

Specialist Tuberculosis and Lung Diseases Hospitals

Rzeszów, 35-241, Poland

Location

Alojzy Pawelec Provincial Hospital of Lung Diseases

Wodzisław Śląski, 44-300, Poland

Location

State Medical Institution: Arkhangelsk Regional Clinical Oncology Center, Chemotherapy department

Arkhangelsk, 163045, Russia

Location

State Therapeutical and Prophylactic Institution: Chelyabinsk Regional Clinical Oncology Center, Chemotherapy Department

Chelyabinsk, 454087, Russia

Location

State Healthcare Institution: Ivanovo Regional Oncology Center, Chemotherapy Department

Ivanovo, 153013, Russia

Location

Non-State Medical Institution: Central Clinical Hospital #2 n.a. N.A. Semashko under OJSC Russian Railways, Chemotherapy Dept.

Moscow, 129128, Russia

Location

State Healthcare Institution: Leningrad Regional Clinical Hospital, Thoracic Surgery Department

Saint Petersburg, 194291, Russia

Location

St. Petersburg State Healthcare Institution: "City Clinical Oncology Center"

Saint Petersburg, 197022, Russia

Location

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, 197101, Russia

Location

State Institution: Samara Regional Clinical Oncology Center, Chemotherapy Department

Samara, 443031, Russia

Location

State Budget Healthcare Institution: Sverdlovsk Regional Oncology Center, Radiotherapy Department

Yekaterinburg, 620036, Russia

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Paclitaxel; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

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

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: November 2, 2010
• First Posted: November 4, 2010
• Study Start: November 1, 2010
• Primary Completion: October 1, 2012
• Study Completion: January 1, 2013
• Last Updated: June 27, 2018

Record last verified: 2018-06

Locations

HU (5); US (10); PL (5); RU (9)