Sym004 in Patients With Advanced Solid Tumors
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01117428|
Recruitment Status : Completed
First Posted : May 5, 2010
Results First Posted : July 12, 2017
Last Update Posted : March 13, 2018
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Colorectal Cancer||Drug: Sym004||Phase 1 Phase 2|
Part A investigates the safety and pharmacokinetics (PK) of escalating weekly dosing of Sym004 in patients with recurrent advanced solid tumors.
Part B and C validates the safety, PK and efficacy of weekly dosing of Sym004 at the maximum tolerated dose (MTD) in a homogenous patient population with advanced metastatic colorectal cancer (mCRC) and wild-type Kirsten rat sarcoma (KRAS). Part B will be initiated when a safe dose has been established in Part A.
If MTD equals 12 mg/kg, then part C will explore the 9 mg/kg level.
Part D and E is to validate the safety, PK and efficacy when administered every 2 weeks at doses of 12 mg/kg and 18 mg/kg, respectively.
Part F is to validate safety, PK and efficacy when administered with a single loading dose of 9 mg/kg followed by weekly doses of 6 mg/kg.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||111 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||An Open-label, Multi-center Phase I Dose Escalation Study to Investigate the Safety and Tolerability of Multiple Doses of Sym004 in Patients With Advanced Solid Tumors|
|Actual Study Start Date :||March 2010|
|Actual Primary Completion Date :||February 2015|
|Actual Study Completion Date :||May 2015|
In part A, patients in all dose cohorts will continue weekly treatment with the assigned dose of Sym004 until disease progression.
In Part B, patients will continue weekly treatment with the tolerated dose of Sym004 until disease progression.
In Part C, patients will receive weekly doses of Sym004 at the dose level below 12 mg/kg i.e. 9 mg/kg until disease progression.
In Part D and E, patients will receive doses of Sym004 administered every 2 weeks at dose level 12 mg/kg and 18 mg/kg, respectively until disease progression.
In Part F, patients will receive a single loading dose of 9 mg/kg followed by weekly doses of 6 mg/kg.
- Number of Participants With Adverse Events (AEs) [ Time Frame: Visit 2 until first follow-up visit (up to 66 weeks) ]The AEs were used as a primary endpoint. AEs were summarized using descriptive statistics and presented overall by system organ class and preferred term. The frequencies of AEs were presented including number and percentages of participants with events and the total number of events.
- Antitumor Activity [ Time Frame: Up to 62 weeks ]Best Overall Response (OR) on the Full Analysis Set (FAS) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, based on central evaluation with confirmatory CT scan or MRI [Complete Response (CR): disappearance of all target lesions; Partial Response (PR): at least a 30% decrease in the sum of diameters of target lesions; Progressive Disease (PD): at least a 20% increase in the sum of diameters of target lesions; Stable Disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; Overall Response (OR): CR + PR]. Baseline was defined as Visit 2 (pre-infusion). The outcome measure was measured from screening until PD.
- Antitumor Activity Endpoints - Time-to-event Endpoints [ Time Frame: Up to 62 weeks ]
Median Progression Free Survival (PFS) was defined as the time interval without PD from start of first infusion until death or documented PD (i.e. at least a 20% increase in the sum of diameters of target lesions) according to RECIST v1.1. Patients who died without confirmed PD were considered as progressed. Patients who died or showed PD more than 21 days after last treatment were censored (i.e. were considered alive without progression on Day 21 after last treatment). Patients without events were censored at date of last scan or 22 days after last treatment, whichever occurred first.
Median Overall Survival (OS) was defined as the time from start of first infusion until date of death from any cause. Patients alive at the time of the analysis or prematurely withdrawn from the trial (e.g. lost to follow-up or consent withdrawn) were censored for the OS analysis. In any case of censoring, the date of censoring was the last time point documenting survival status.
- Terminal Half-Life (T½) [ Time Frame: See Time Frame in the Outcome Measure Description ]
For Part A, the endpoint was not calculated. For Parts B, C and F, the endpoint was calculated for each patient following the first and fourth Sym004 infusions.
For Parts D and E, the endpoint was calculated for each patient following the first and third Sym004 infusions.
T½ was estimated using non-compartmental methods and actual time points.
Outcome Measure Time Frame:
Parts B, C and F (Weekly dosing): Sample collection at Visit 2 (1st dose from end of infusion, 1-, 2-, 4-, 8-, 24-, 48-hours) until 1 week post-infusion (168-hours) and at Visit 5 (4th dose from end of infusion, 1-, 2-, 4-, 8-, 24-hours) until 1 week post-infusion (168-hours).
Parts D, E (Dosing every second week): Sample collection at Visit 2 (1st dose from end of infusion, 1-, 2-, 4-, 8-, 24-, 48-hours) to end of 3rd dose (from end of infusion, 1-, 2-, 4-, 8-, 24-hours) until 2 weeks post-infusion (336 hours).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01117428
|United States, Texas|
|South Texas Accelerated Research Therapeutics (START)|
|San Antonio, Texas, United States, 78229|
|UZ Brussel, Medische Oncologie|
|Brussel, Belgium, 1090|
|UZ Gasthuisberg, Digestive Oncology Unit|
|Brussel, Belgium, 3000|
|UZ Antwerp, Oncologie|
|Edegem, Belgium, 2650|
|Medical Oncology Department, Vall d´Hebron University Hospital|
|Barcelona, Spain, 08035|
|Servicio de Oncología Médica, Hospital Universitario Virgen del Rocío|
|Sevilla, Spain, 41013|
|Hospital Clínico Universitario de Valencia|
|Valencia, Spain, 46010|
|Principal Investigator:||Josep Tabernero, MD, PhD||Vall d´Hebron University Hospital|