A Multinational, Randomized, Open-Label Study of Custirsen In Patients With Advanced or Metastatic (Stage IV) Non-Small Cell Lung Cancer

Non-Small Cell Lung Cancer Clinical Trial

Official title:

A Multinational, Randomized, Open-Label Phase III Study of Custirsen (TV-1011/OGX-011) In Combination With Docetaxel Versus Docetaxel As A Second-Line Treatment In Patients With Advanced or Metastatic (Stage IV) Non-Small Cell Lung Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01630733
• Other study ID #: TV1011-LC-303
• Secondary ID: 2012-002447-14
• Status: Recruiting
• Phase: Phase 3
• First received: June 26, 2012
• Last updated: June 29, 2016
• Start date: September 2012
• Est. completion date: July 2017

Study information

• Verified date: June 2016
• Source: OncoGenex Technologies
• Contact: Oncogenex Pharmaceuticals
• Phone: (425) 686-1500
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 700
• Est. completion date: July 2017
• Est. primary completion date: July 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patients must have a histologically or cytologically confirmed, unresectable, advanced or metastatic (Stage IV per AJCC 7th edition TNM staging) NSCLC

2. Males or females = 18 years of age at screening.

3. Life expectancy of > 12 weeks from screening, according to the investigator's assessment.

4. 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.

5. Patients must have documented radiological disease progression either during or after the first-line therapy.

6. Patients must have at least one measurable lesion per RECIST 1.1 criteria.

7. ECOG performance status of 0 or 1 at screening.

8. 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

9. 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).

10. Females of child-bearing potential must have negative serum pregnancy test within 72 hours before randomization.

11. 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.

12. 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.

Exclusion Criteria:

1. Patients treated with any systemic anti-cancer therapy for NSCLC within 21 days prior to randomization (6 weeks for Bevacizumab).

2. Radiotherapy = 2 weeks prior to randomization. Patients must have recovered from all radiotherapy-related toxicities.

3. Major surgical procedure within 4 weeks prior to randomization. Patient must have recovered from all surgery-related complications.

4. 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).

5. 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).

6. 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.

7. 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.

8. Planned concomitant participation in another clinical trial of an experimental agent, vaccine, or device. Concomitant participation in observational studies is acceptable.

9. Female patients who are breastfeeding.

10. Patients previously treated with docetaxel for NSCLC or with known severe hypersensitivity to taxane therapies.

11. Patients with known and documented EGFR mutation who have not received an EGFR inhibitor.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

Drug:
• Custirsen
Custirsen: Three loading doses of custirsen 640 mg 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
Docetaxel: 75 mg/m2 IV over 1 hour on Day 1 of every 21-day cycle

Locations

Country	Name	City	State
Australia	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	Port Macquarie Base Hospital	Port Macquarie
Australia	Border Medical Oncology	Wodonga
Australia	The Queen Elizabeth Hospital	Woodville
Germany	Asklepios Fachkliniken GmbH	Gauting
Germany	Martha-Maria Krankenhaus Halle-Dolau gGmbH	Halle (Saale)
Germany	Klinikum Kassel	Kassel
Germany	Kliniken der Stadt Koln gGmbH	Koeln
Hungary	Orszagos Koranyi TBC es Pulmonologiai Intezet	Budapest
Hungary	Országos Korányi TBC és Pulmonológiai Intézet	Budapest
Hungary	Uzsoki Utcai Korhaz	Budapest
Hungary	Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet	Szolnok
Israel	Meir Medical Center	Kfar Saba
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Italy	Az. Osp. Univ. Ospedali Riuniti Umberto I G.M. Lancisi G.Salesi	Ancona
Italy	Azienda Ospedaliera Papa Giovanni XXIII	Bergamo
Italy	Azienda Ospedaliera Istituti Ospitalieri	Cremona
Italy	Istituto Nazionale per la Ricerca sul Cancro	Genova
Italy	Ospedale Livorno	Livorno
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
Korea, Republic of	Kosin University Gospel Hospital	Busan
Korea, Republic of	Keimyung University Dongsan Medical Center	Daegu
Korea, Republic of	Gachon University Gil Hospital	Incheon
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	Samsung Medical Center	Seoul
New Zealand	Christchurch Hospital	Christchurch
New Zealand	Palmerston North Hospital	Palmerston North
Poland	Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc w Olsztynie	Olsztyn
Poland	Med-Polonia Sp. z o.o.	Poznan
Poland	Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. K. Marcinkowskiego w Poznaniu	Poznan
Poland	Specjalistyczny Szpital im. Alfreda Sokolowskiego	Szczecin
Russian Federation	Arkhangelsk Regional Clinical Oncology Dispensary	Arkhangelsk
Russian Federation	Federal State Institution Medical Radiology Research Center	Obninsk
Russian Federation	Oncology Centre Number 2	Sochi
Russian Federation	Consorcio Hospitalario Provincial de Castellon	St. Petersburg
Russian Federation	Leningrad Regional Clinical Hospital	St. Petersburg
Singapore	SOC Clinic @ Farrer Park	Singapore
Spain	Fundacion Hospital de Alcorcon	Alcorcon
Spain	Hospital del Mar	Barcelona
Spain	Consorcio Hospitalario Provincial de Castellon	Castellon
Spain	Hospital Universitario Insular Materno-Infantil de Las Palmas	Las Palmas de G.C.
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Puerta de Hierro	Majadahonda-Madrid
Spain	Corporacio Sanitaria Parc Tauli	Sabadell
Spain	Hospital Universitario Doctor Peset	Valencia
Taiwan	Changhua Christian Hospital	Changhua City
Taiwan	China Medical University Hospital	Taichung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	National Cheng Kung University Hosptial	Tainan
Taiwan	Tri-Service General Hospital	Taipei
Thailand	Prapokklao Hospital	Chanthaburi
Thailand	Songklanagarind Hospital Prince of Songkla University	Hat Yai, Songkhla
Thailand	Maharat Nakhonratchasima Hospital	Nakhon Ratchasima
Thailand	National Cancer Institute	Phayathai, Bangkok
Thailand	Buddhachinnaraj Hospital	Phisanulok
Thailand	Saraburi Regional Hospital	Saraburi
Ukraine	Municipal Institution Clinical Oncology Dispensary of Dnipropetrovsk Regional Council	Dnipropetrovsk
Ukraine	Municipal institution Multifield City Clinical Hospital Numero 4 of Dnipropetrovsk Regional Council	Dnipropetrovsk
Ukraine	MIHC Kharkiv Regional Clinical Oncology Center	Kharkiv
Ukraine	Ukrainian Medical Stomatological Academy	Poltava
Ukraine	Regional Municipal Institution Sumy Regional Clinical Oncology Dispensary	Sumy
Ukraine	Uzhgorod Central City Clinical Hospital	Uzhgorod
Ukraine	Vinnytsya Regional Clinical Oncology Dispensary	Vinnytsya
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Virginia Cancer Specialists PC	Fairfax	Virginia
United States	Kentucky Cancer Clinic	Hazard	Kentucky
United States	Joliet Oncology-Hematology Associates Ltd.	Joliet	Illinois
United States	Center for Biomedical Research LLC	Knoxville	Tennessee
United States	Florida Hospital	Orlando	Florida
United States	University Cancer Institute	Soynton Beach	Florida
United States	Missouri Baptist Cancer Center	St. Louis	Missouri
United States	Blood and Cancer Center of East Texas	Tyler	Texas
United States	Novant Health	Winston Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
OncoGenex Technologies

Countries where clinical trial is conducted

United States,  Australia,  Germany,  Hungary,  Israel,  Italy,  Korea, Republic of,  New Zealand,  Poland,  Russian Federation,  Singapore,  Spain,  Taiwan,  Thailand,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival	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.	60 months	No
Secondary	Progression Free Survival per RECIST v1.1	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.	60 months	No
Secondary	Objective Response Rate as defined by RECIST v1.1.	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.	60 months	No
Secondary	Duration of Disease Control	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.	60 months	No
Secondary	Adverse events	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.	60 months	Yes
Secondary	Duration of Objective Response	The evaluation of overall response at each assessment is a composite of target lesion response, non-target lesion response, presence of new lesions.	60 months	No
Secondary	Disease Control Rate	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.)	60 months	No