Clinical trial NCT01117428: Sym004 in Patients With Advanced Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Metastatic Colorectal Cancer
Keywords: Advanced solid tumors
Metastatic colorectal Cancer
Lead sponsor: Symphogen A/S
Sponsor class: INDUSTRY
First posted: 2010-05-05
Enrollment: 111
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This trial is designed as a multi-centre, open label, dose-escalation, phase I trial and consists of five parts.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

Part A:

1. Patients with refractory or recurrent advanced late stage solid tumors without available therapeutic options .

Part B, C, D, E and F:

1. Patients with refractory or recurrent advanced mCRC and wild-type KRAS who have progressed on epidermal growth factor receptor (EGFR) Ab treatment.
2. Patients wit confirmed response while on treatment anti-EGFR Ab treatment.
3. Documented disease progression during or within 6 months after cessation of anti-EGFR Ab treatment.
4. Patients must be willing to have a biopsy performed from a tumor lesion at screening and at Visit 6.

Part A, B, C, D, E and F:

1. Histologically or cytologically confirmed diagnosis of cancer
2. Failure and/or intolerance to standard chemotherapy
3. Life expectancy of at least 3 months
4. Eastern Cooperative Oncology Group (ECOG) performance status ≤2

Exclusion Criteria:

1. Patients with clinically symptomatic brain metastases.
2. Received the following treatments prior to Visit 2:

   * Cytotoxic or cytostatic anti-cancer chemotherapy within 4 weeks
   * Total resection or irradiation of the target lesion
   * Antibody therapy within 4 weeks and vaccines within 12 weeks
   * Tyrosin kinase inhibitors within 4 weeks
   * Any investigational agent within 4 weeks
3. Diarrhea CTCAE \>1
4. Skin rash CTCAE \>1
5. Abnormal organ or bone marrow function.
6. Use of immunosuppressive agents for the past 4 weeks prior to trial start, including systemic corticosteroids used at doses above 20mg/day of prednisolone or equivalent.
7. History of other malignancy within 5 years prior to trial start, with the exception of basal cell carcinoma of the skin and carcinoma in situ of the cervix (not in Part A).
8. Active severe infection, any other concurrent disease or medical conditions that are deemed to interfere with the conduct of the trial as judged by the investigator.
9. Known HIV positive
10. Known active hepatitis B or C
11. Patients with known uncontrolled allergic conditions or allergy to the study drug and/or their components.
12. Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months from Visit 1, congestive heart failure, and arrhythmia requiring therapy, with the exception of extra systoles or minor conduction abnormalities and controlled and well treated chronic atrial fibrillation.
13. Significant concurrent, uncontrolled medical condition evaluated by the investigator to interfere with effect of the trial drug.

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Visit 2 until first follow-up visit (up to 66 weeks)
Secondary outcomes:
measure: Antitumor Activity
timeFrame: Up to 62 weeks
measure: Antitumor Activity Endpoints - Time-to-event Endpoints
timeFrame: Up to 62 weeks
measure: Terminal Half-Life (T½)
timeFrame: See Time Frame in the Outcome Measure Description
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics (START)
state: Texas
city: Brussel
country: Belgium
facility: UZ Brussel, Medische Oncologie
city: Brussel
country: Belgium
facility: UZ Gasthuisberg, Digestive Oncology Unit
city: Edegem
country: Belgium
facility: UZ Antwerp, Oncologie
city: Barcelona
country: Spain
facility: Medical Oncology Department, Vall d´Hebron University Hospital
city: Sevilla
country: Spain
facility: Servicio de Oncología Médica, Hospital Universitario Virgen del Rocío
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
Study officials:
affiliation: Vall d´Hebron University Hospital
name: Josep Tabernero, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dienstmann R, Patnaik A, Garcia-Carbonero R, Cervantes A, Benavent M, Rosello S, Tops BB, van der Post RS, Argiles G, Skartved NJ, Hansen UH, Hald R, Pedersen MW, Kragh M, Horak ID, Braun S, Van Cutsem E, Tolcher AW, Tabernero J. Safety and Activity of the First-in-Class Sym004 Anti-EGFR Antibody Mixture in Patients with Refractory Colorectal Cancer. Cancer Discov. 2015 Jun;5(6):598-609. doi: 10.1158/2159-8290.CD-14-1432. Epub 2015 May 11.