Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Sym004 in Patients With Advanced Solid Tumors

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
Symphogen A/S Identifier:
First received: April 23, 2010
Last updated: September 29, 2014
Last verified: September 2014

This trial is designed as a multi-centre, open label, dose-escalation, phase I trial and consists of five parts. Part A investigates the safety and 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 MTD in a homogenous patient population with advanced mCRC and wild-type KRAS. If MTD equals 12 mg/kg, then part C will explore the 9 mg/kg level. Part B will be initiated when a safe dose has been established in Part A. 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 9 mg/kg followed by weekly doses of 6 mg/kg.

Condition Intervention Phase
Metastatic Colorectal Cancer
Biological: Sym004
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:

Further study details as provided by Symphogen A/S:

Primary Outcome Measures:
  • Adverse events [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
    DLTs (DLT period of 4 weeks after first dose in each patient) along with; incidence and severity of Adverse Events (AEs), including Serious Adverse Events (SAEs) and Suspected Unexpected Serious Adverse Reactions (SUSARs) during the entire trial period.

Secondary Outcome Measures:
  • Objective tumor response according to RECIST criteria verified by imaging techniques [ Time Frame: 01/02/2010 to 31/07/2014 ] [ Designated as safety issue: No ]
  • Duration of overall response [ Time Frame: 01/02/2010 to 31/07/2014 ] [ Designated as safety issue: No ]
  • Progression free survival [ Time Frame: 01/02/2010 to 31/07/2014 ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 01/02/2010 to 31/07/2014 ] [ Designated as safety issue: No ]
  • Host immune response: ADA monitoring [ Time Frame: 01/02/2010 to 31/07/2014 ] [ Designated as safety issue: No ]
  • Skin rash according to CTCAE grading [ Time Frame: 01/02/2010 to 31/07/2014 ] [ Designated as safety issue: No ]
  • Biomarker including CEA and YKL 40 [ Time Frame: 01/02/2010 to 31/07/2014 ] [ Designated as safety issue: No ]
  • Vital signs and laboratory parameters [ Time Frame: 01/02/2010 to 31/07/2014 ] [ Designated as safety issue: No ]
  • Pharmakokinetic profile of multiple weekly and biweekly doses of Sym004 [ Time Frame: 24/08/2010 to 31/07/2014 ] [ Designated as safety issue: No ]

Estimated Enrollment: 110
Study Start Date: March 2010
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment Biological: Sym004

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.

Other Name: Sym004


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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 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. 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: 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
Sponsors and Collaborators
Symphogen A/S
Principal Investigator: Josep Tabernero, Dr. Hospital Vall d'Hebron BCN ES
  More Information

No publications provided

Responsible Party: Symphogen A/S Identifier: NCT01117428     History of Changes
Other Study ID Numbers: Sym004-01, 2009-017119-13
Study First Received: April 23, 2010
Last Updated: September 29, 2014
Health Authority: United States: Food and Drug Administration
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Belgium: Federal Agency for Medicinal Products and Health Products

Keywords provided by Symphogen A/S:
Advanced solid tumors
Metastatic colorectal Cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms by Site
Rectal Diseases processed this record on November 27, 2014