Sym004 in Patients With Advanced Solid Tumors

NCT ID: NCT01117428

Last Updated: 2018-10-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 111 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-03-31
• Study Completion Date: 2015-05-31

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.

Conditions

Metastatic Colorectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sym004

Group Type: EXPERIMENTAL

Sym004

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Symphogen A/S

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Josep Tabernero, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Vall d´Hebron University Hospital

Locations

South Texas Accelerated Research Therapeutics (START)

San Antonio, Texas, United States

UZ Brussel, Medische Oncologie

Brussels, , Belgium

UZ Gasthuisberg, Digestive Oncology Unit

Brussels, , Belgium

UZ Antwerp, Oncologie

Edegem, , Belgium

Medical Oncology Department, Vall d´Hebron University Hospital

Barcelona, , Spain

Servicio de Oncología Médica, Hospital Universitario Virgen del Rocío

Seville, , Spain

Hospital Clínico Universitario de Valencia

Valencia, , Spain

Countries

United States; Belgium; Spain

References

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.

Reference Type: DERIVED

PMID: 25962717 (View on PubMed)

Other Identifiers

2009-017119-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

Sym004-01

Identifier Type: -

Identifier Source: org_study_id