Clinical trial NCT01584830: Asian Subjects With Metastatic Colorectal Cancer Treated With Regorafenib or Placebo After Failure of Standard Therapy
Official title: A Randomized, Double-blind, Placebo-controlled Phase III Study of Regorafenib Plus Best Supportive Care (BSC) Versus Placebo Plus BSC in Asian Subjects With Metastatic Colorectal Cancer (CRC) Who Have Progressed After Standard Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Colorectal Neoplasms
Keywords: Regorafenib
Colorectal
Metastatic
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2012-04-25
Enrollment: 204
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess if Regorafenib in combination with best supportive care will slow down tumor progression and result in increased survival in patients with metastatic colorectal cancer.


Eligibility criteria: Inclusion Criteria:

* Histological or cytological documentation of adenocarcinoma of the colon or rectum. All other histological types are excluded.
* Subjects with metastatic colorectal cancer(CRC) (Stage IV).
* Subjects must have failed at least two lines of prior treatment.
* Progression during or within 3 months following the last administration of approved standard therapies which must include a fluoropyrimidine, oxaliplatin and irinotecan.

  * Subjects treated with oxaliplatin in an adjuvant setting should have progressed during or within 6 months of completion of adjuvant therapy.
  * Subjects who progress more than 6 months after completion of oxaliplatin containing adjuvant treatment must be retreated with oxaliplatin-based therapy to be eligible.
  * Subjects who have withdrawn from standard treatment due to unacceptable toxicity warranting discontinuation of treatment and precluding retreatment with the same agent prior to progression of disease will also be allowed into the study.
  * Subjects may have received prior treatment with Avastin (bevacizumab) and/or Erbitux (cetuximab)/Vectibix (panitumumab) (if KRAS WT)
* Metastatic CRC subjects must have measurable or non measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, version 1.1.
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 1.
* Life expectancy of at least 3 months.
* Adequate bone marrow, liver and renal function as assessed by the laboratory required by protocol.

Exclusion Criteria:

* Prior treatment with Regorafenib.
* Previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years prior to randomization EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors \[Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)\].
* Extended field radiotherapy within 4 weeks or limited field radiotherapy within 2 weeks prior to randomization.
* Cardiological disease including Congestive heart failure, Unstable angina, Myocardial infarction, Cardiac arrhythmias requiring anti-arrhythmic therapy.
* Uncontrolled hypertension. (Systolic blood pressure 150 mmHg or diastolic pressure 90 mmHg despite optimal medical management).
* Subjects with phaeochromocytoma.
* Pleural effusion or ascites that causes respiratory compromise.
* Arterial or venous thrombotic or embolic events.
* Any history of or currently known brain metastases.
* Interstitial lung disease with ongoing signs and symptoms at the time of informed consent.
* Systemic anticancer therapy including cytotoxic therapy, signal transduction inhibitors, immunotherapy, and hormonal therapy during this trial or within 4 week.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: From randomization of the first subject untill 154 death events observed, up to 2 years
Secondary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: From randomization of the first subject untill 154 death events observed, up to 2 years
measure: The percentage of subjects with total number of Complete Response (CR) + total number of Partial Response (PR).
timeFrame: From randomization of the first subject untill 154 death events observed, up to 2 years
measure: Disease Control Rate (DCR)
timeFrame: From randomization of the first subject untill 154 death events observed, up to 2 years
measure: Safety variables will be summarized using descriptive statistics based on adverse events collection
timeFrame: From randomization of the first subject untill 154 death events observed, up to 2 years
Other outcomes:
Locations:
city: Guangzhou
country: China
state: Guangdong
city: Guangzhou
country: China
state: Guangdong
city: Harbin
country: China
state: Heilongjiang
city: Nanjing
country: China
state: Jiangsu
city: Xi'an
country: China
state: Shaanxi
city: Qingdao
country: China
state: Shandong
city: Chengdu
country: China
state: Sichuan
city: Hangzhou
country: China
state: Zhejiang
city: Beijing
country: China
city: Beijing
country: China
city: Beijing
country: China
city: Changchun
country: China
city: Shanghai
country: China
city: Shanghai
country: China
city: Shanghai
country: China
city: Tianjin
country: China
city: Shatin
country: Hong Kong
state: New Territories
city: Hong Kong
country: Hong Kong
city: Seoul
country: Korea, Republic of
state: Korea
city: Taipei
country: Taiwan
city: Taipei
country: Taiwan
city: Taoyuan
country: Taiwan
city: Hanoi
country: Vietnam
city: Hcmc
country: Vietnam
city: Ho Chi Minh City
country: Vietnam
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Li J, Qin S, Xu R, Yau TC, Ma B, Pan H, Xu J, Bai Y, Chi Y, Wang L, Yeh KH, Bi F, Cheng Y, Le AT, Lin JK, Liu T, Ma D, Kappeler C, Kalmus J, Kim TW; CONCUR Investigators. Regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer (CONCUR): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2015 Jun;16(6):619-29. doi: 10.1016/S1470-2045(15)70156-7. Epub 2015 May 13.