A Multinational, Randomized, Open-Label Study of Custirsen In Patients With Advanced or Metastatic (Stage IV) Non-Small Cell Lung Cancer
- Registration Number
- NCT01630733
- Lead Sponsor
- Achieve Life Sciences
- Brief Summary
The primary objective of the study is to compare overall survival of patients randomized to receiving custirsen in combination with docetaxel (Arm A) with patients randomized to receive docetaxel alone (Arm B).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 700
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Patients must have a histologically or cytologically confirmed, unresectable, advanced or metastatic (Stage IV per AJCC 7th edition TNM staging) NSCLC
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Males or females ≥ 18 years of age at screening.
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Life expectancy of > 12 weeks from screening, according to the investigator's assessment.
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Patients must have received one prior line of platinum-based systemic anticancer therapy for advanced or metastatic NSCLC. Prior maintenance therapy is allowed and will be considered as the same line of therapy when continued at the end of a treatment regimen.
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Patients must have documented radiological disease progression either during or after the first-line therapy.
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Patients must have at least one measurable lesion per RECIST 1.1 criteria.
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ECOG performance status of 0 or 1 at screening.
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Have adequate values, bone marrow, renal and liver functions at screening as defined below:
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- Platelet count ≥ 100 x 109/L
- Hemoglobin ≥ 9 g/dL
- Serum creatinine ≤ 1.5 x upper limit of normal (ULN)
- Total Bilirubin ≤ 1.0 x ULN (unless elevated secondary to benign conditions such as Gilbert's disease)
- AST and ALT ≤ 1.5 x ULN
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Resolution of any toxic effects of prior therapy to Grade ≤1 according to NCI CTCAE, version 4.0 (exception of alopecia and ≤ Grade 2 peripheral neuropathy).
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Females of child-bearing potential must have negative serum pregnancy test within 72 hours before randomization.
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Women of child-bearing potential will practice a highly effective method of birth control during and for 3 months after the chemotherapy/ custirsen last dose. Men of reproductive potential who are not surgically sterile must agree to abstain from sexual activity or use medically accepted and highly effective method of contraception during and for 6 months after the chemotherapy/custirsen last dose.
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Patients must be willing and able to give written informed consent prior to any protocol-specific procedures being performed and comply with the protocol requirements for the duration of the study.
- Patients treated with any systemic anti-cancer therapy for NSCLC within 21 days prior to randomization (6 weeks for Bevacizumab).
- Radiotherapy ≤ 2 weeks prior to randomization. Patients must have recovered from all radiotherapy-related toxicities.
- Major surgical procedure within 4 weeks prior to randomization. Patient must have recovered from all surgery-related complications.
- Patients with known CNS metastases (Patients with any clinical signs of CNS metastases must have a CT or MRI of the brain to rule out CNS metastases in order to be eligible for participation in the study). Patients who have had brain metastases treated with radiotherapy or surgically removed with no residual disease confirmed by imaging; patients should be clinically stable and off corticosteroid treatment at least 3 weeks prior to randomization).
- Patients with current diagnosis or a history of another active primary malignancy (except in situ carcinoma of the cervix, adequately treated non-melanomatous skin cancers, clinically localized prostate cancer, superficial bladder cancer or other malignancy treated at least 5 years previously with no evidence of recurrence).
- Severe or unstable medical conditions such as heart failure, ischemic heart disease, uncontrolled hypertension, uncontrolled diabetes mellitus, psychiatric condition, as well as an ongoing cardiac arrhythmia requiring medication (≥ Grade 2, according to NCI CTCAE v4.0) or any other significant or unstable concurrent medical illness that in the opinion of the Investigator would preclude protocol therapy.
- A history of events such as myocardial infarction, cerebrovascular accident or acute hepatitis within 3 months of randomization or treatment of a major active infection within one month of randomization, or any other significant event that in the opinion of the Investigator would preclude protocol therapy.
- Planned concomitant participation in another clinical trial of an experimental agent, vaccine, or device. Concomitant participation in observational studies is acceptable.
- Female patients who are breastfeeding.
- Patients previously treated with docetaxel for NSCLC or with known severe hypersensitivity to taxane therapies.
- Patients with known and documented EGFR mutation who have not received an EGFR inhibitor.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Custirsen + Docetaxel Docetaxel Custirsen: Three loading doses of custirsen 640mg IV over 2 hours administered in 5 to 9 days prior to Day 1 of Cycle 1, then custirsen 640 mg IV weekly every 21-day cycle Docetaxel: 75 mg/m2 IV over 1 hour on Day 1 of every 21-day cycle Docetaxel Docetaxel Docetaxel: 75 mg/m2 IV over 1 hour on Day 1 of every 21-day cycle Continue treatment until disease progression, unacceptable toxicity, withdrawal of consent or protocol specified parameters to stop treatment. Custirsen + Docetaxel Custirsen Custirsen: Three loading doses of custirsen 640mg IV over 2 hours administered in 5 to 9 days prior to Day 1 of Cycle 1, then custirsen 640 mg IV weekly every 21-day cycle Docetaxel: 75 mg/m2 IV over 1 hour on Day 1 of every 21-day cycle
- Primary Outcome Measures
Name Time Method Overall Survival 60 months Primary endpoint and variable for the study is overall survival (OS), defined as the time from date of randomization to the date of death from any cause.
- Secondary Outcome Measures
Name Time Method Duration of Disease Control 60 months The Duration of Disease Control is defined as the time from randomization to the date of the first documented disease progression (taking as reference for progressive disease the smallest measurements recorded on study) or death, whichever occurs first.
Adverse events 60 months Adverse events and concomitant medications will be collected throughout the study up to 28 days after the last dose of study treatment. Medical history will be assessed, mutation status will be collected, if available, and an electrocardiogram will be performed at screening. Physical examination, vital signs, and laboratory evaluations will be conducted at screening and throughout the study.
Duration of Objective Response 60 months The evaluation of overall response at each assessment is a composite of target lesion response, non-target lesion response, presence of new lesions.
Objective Response Rate as defined by RECIST v1.1. 60 months Objective Response (OR) is defined as achieving a best overall response of complete response (CR) or partial response (PR), as defined using RECIST v1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Disease Control Rate 60 months The disease control rate will be calculated as the total number of patients in each group with best overall response of CR, PR or Stable Disease (SD) divided by the total number of randomized patients in the group and will be compared similarly as Objective Response Rate (ORR.)
Progression Free Survival per RECIST v1.1 60 months Progression Free Survival: time from date of randomization to first objective documented progression per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 or death due to any cause, whichever occurs first. Tumor lesions measured in at least one dimension with minimum size of 10 mm by CT scan, 10 mm caliper by clinical exam. Malignant lymph nodes must be \>15 mm in short axis when assessed by CT scan. All measurable lesions up to a maximum of 2 lesions per organ and 5 in total representative of all involved organs should be identified as target lesions and measured and recorded.
Trial Locations
- Locations (81)
Hospital Universitario La Paz
🇪🇸Madrid, Spain
University Cancer Institute
🇺🇸Soynton Beach, Florida, United States
Hospital Universitario Doctor Peset
🇪🇸Valencia, Spain
Corporacio Sanitaria Parc Tauli
🇪🇸Sabadell, Spain
Hospital Universitario Puerta de Hierro
🇪🇸Majadahonda-Madrid, Spain
Ospedale Livorno
🇮🇹Livorno, Italy
National Cheng Kung University Hosptial
🇨🇳Tainan, Taiwan
Joliet Oncology-Hematology Associates Ltd.
🇺🇸Joliet, Illinois, United States
Kentucky Cancer Clinic
🇺🇸Hazard, Kentucky, United States
Novant Health
🇺🇸Winston Salem, North Carolina, United States
Missouri Baptist Cancer Center
🇺🇸St. Louis, Missouri, United States
Blood and Cancer Center of East Texas
🇺🇸Tyler, Texas, United States
Virginia Cancer Specialists PC
🇺🇸Fairfax, Virginia, United States
Flinders Medical Centre
🇦🇺Bedford Park, Australia
Austin Health
🇦🇺Heidelberg, Australia
Royal Hobart Hospital
🇦🇺Hobart, Australia
St George Hospital
🇦🇺Kogarah, Australia
Cabrini Hospital Malvern
🇦🇺Malvern, Australia
Border Medical Oncology
🇦🇺Wodonga, Australia
The Queen Elizabeth Hospital
🇦🇺Woodville, Australia
Asklepios Fachkliniken GmbH
🇩🇪Gauting, Germany
Kliniken der Stadt Koln gGmbH
🇩🇪Koeln, Germany
Orszagos Koranyi TBC es Pulmonologiai Intezet
🇭🇺Budapest, Hungary
Uzsoki Utcai Korhaz
🇭🇺Budapest, Hungary
Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet
🇭🇺Szolnok, Hungary
Meir Medical Center
🇮🇱Kfar Saba, Israel
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Az. Osp. Univ. Ospedali Riuniti Umberto I G.M. Lancisi G.Salesi
🇮🇹Ancona, Italy
Azienda Ospedaliera Istituti Ospitalieri
🇮🇹Cremona, Italy
Azienda Ospedaliera Papa Giovanni XXIII
🇮🇹Bergamo, Italy
Istituto Nazionale per la Ricerca sul Cancro
🇮🇹Genova, Italy
Azienda Ospedaliera - Ospedale San Carlo Borromeo
🇮🇹Milano, Italy
Azienda Ospedaliera Niguarda Ca Granda
🇮🇹Milano, Italy
Azienda Ospedaliero Universitaria di Parma
🇮🇹Parma, Italy
IRCCS Policlinico San Matteo
🇮🇹Pavia, Italy
Kosin University Gospel Hospital
🇰🇷Busan, Korea, Republic of
Keimyung University Dongsan Medical Center
🇰🇷Daegu, Korea, Republic of
Chonnam National University Hwasun Hospital
🇰🇷Jeonnam, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam, Korea, Republic of
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Christchurch Hospital
🇳🇿Christchurch, New Zealand
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Palmerston North Hospital
🇳🇿Palmerston North, New Zealand
Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc w Olsztynie
🇵🇱Olsztyn, Poland
Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. K. Marcinkowskiego w Poznaniu
🇵🇱Poznan, Poland
Specjalistyczny Szpital im. Alfreda Sokolowskiego
🇵🇱Szczecin, Poland
Arkhangelsk Regional Clinical Oncology Dispensary
🇷🇺Arkhangelsk, Russian Federation
Oncology Centre Number 2
🇷🇺Sochi, Russian Federation
Leningrad Regional Clinical Hospital
🇷🇺St. Petersburg, Russian Federation
SOC Clinic @ Farrer Park
🇸🇬Singapore, Singapore
Fundacion Hospital de Alcorcon
🇪🇸Alcorcon, Spain
Hospital del Mar
🇪🇸Barcelona, Spain
Hospital Universitario Insular Materno-Infantil de Las Palmas
🇪🇸Las Palmas de G.C., Spain
National Cancer Institute
🇹🇭Phayathai, Bangkok, Thailand
Municipal institution Multifield City Clinical Hospital Numero 4 of Dnipropetrovsk Regional Council
🇺🇦Dnipropetrovsk, Ukraine
Regional Municipal Institution Sumy Regional Clinical Oncology Dispensary
🇺🇦Sumy, Ukraine
Med-Polonia Sp. z o.o.
🇵🇱Poznan, Poland
Federal State Institution Medical Radiology Research Center
🇷🇺Obninsk, Russian Federation
Center for Biomedical Research LLC
🇺🇸Knoxville, Tennessee, United States
Buddhachinnaraj Hospital
🇹🇭Phisanulok, Thailand
Municipal Institution Clinical Oncology Dispensary of Dnipropetrovsk Regional Council
🇺🇦Dnipropetrovsk, Ukraine
Uzhgorod Central City Clinical Hospital
🇺🇦Uzhgorod, Ukraine
Országos Korányi TBC és Pulmonológiai Intézet
🇭🇺Budapest, Hungary
Tri-Service General Hospital
🇨🇳Taipei, Taiwan
Changhua Christian Hospital
🇨🇳Changhua City, Taiwan
Prapokklao Hospital
🇹🇭Chanthaburi, Thailand
Songklanagarind Hospital Prince of Songkla University
🇹🇭Hat Yai, Songkhla, Thailand
Maharat Nakhonratchasima Hospital
🇹🇭Nakhon Ratchasima, Thailand
Saraburi Regional Hospital
🇹🇭Saraburi, Thailand
MIHC Kharkiv Regional Clinical Oncology Center
🇺🇦Kharkiv, Ukraine
China Medical University Hospital
🇨🇳Taichung, Taiwan
Taichung Veterans General Hospital
🇨🇳Taichung, Taiwan
Ukrainian Medical Stomatological Academy
🇺🇦Poltava, Ukraine
Vinnytsya Regional Clinical Oncology Dispensary
🇺🇦Vinnytsya, Ukraine
Consorcio Hospitalario Provincial de Castellon
🇪🇸Castellon, Spain
Gachon University Gil Hospital
🇰🇷Incheon, Korea, Republic of
Martha-Maria Krankenhaus Halle-Dolau gGmbH
🇩🇪Halle (Saale), Germany
Klinikum Kassel
🇩🇪Kassel, Germany
Port Macquarie Base Hospital
🇦🇺Port Macquarie, Australia
MetroHealth Medical Center
🇺🇸Cleveland, Ohio, United States
Florida Hospital
🇺🇸Orlando, Florida, United States