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Metastatic Colorectal CancerPhase 1/2NCT01117428

Sym004 in Patients With Advanced Solid Tumors

A Phase 1/2 study testing Sym004 in people with Metastatic Colorectal Cancer, run by Symphogen A/S at 7 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This trial is designed as a multi-centre, open label, dose-escalation, phase I trial and consists of five parts. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Colorectal Cancer
What is being tested?
Sym004
Could I receive a placebo?
No, everyone receives an active treatment
How many people
111 participants
Where
7 sitesin 3 countries
Study dates
Mar 2010to May 2015
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Part A:
  • 1. Patients with refractory or recurrent advanced late stage solid tumors without available therapeutic options .
  • Part B, C, D, E and F:
  • Patients with refractory or recurrent advanced mCRC and wild-type KRAS who have progressed on epidermal growth factor receptor (EGFR) Ab treatment.
  • Patients wit confirmed response while on treatment anti-EGFR Ab treatment.
  • Documented disease progression during or within 6 months after cessation of anti-EGFR Ab treatment.
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  • 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:
  • Histologically or cytologically confirmed diagnosis of cancer
  • Failure and/or intolerance to standard chemotherapy
  • Life expectancy of at least 3 months
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤2

Who cannot join

  • Patients with clinically symptomatic brain metastases.
  • 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
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  • Any investigational agent within 4 weeks
  • Diarrhea CTCAE >1
  • Skin rash CTCAE >1
  • Abnormal organ or bone marrow function.
  • 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.
  • 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).
  • 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.
  • Known HIV positive
  • Known active hepatitis B or C
  • Patients with known uncontrolled allergic conditions or allergy to the study drug and/or their components.
  • 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.
  • Significant concurrent, uncontrolled medical condition evaluated by the investigator to interfere with effect of the trial drug.

Trial locations and contacts

7 sites in 3 countries.

7 sites in 3 countries

Belgium3 sites

  • UZ Brussel, Medische Oncologie

    Brussels, 1090

  • UZ Gasthuisberg, Digestive Oncology Unit

    Brussels, 3000

  • UZ Antwerp, Oncologie

    Edegem, 2650

Other trials in Belgium

Spain3 sites

  • Medical Oncology Department, Vall d´Hebron University Hospital

    Barcelona, 08035

  • Servicio de Oncología Médica, Hospital Universitario Virgen del Rocío

    Seville, 41013

  • Hospital Clínico Universitario de Valencia

    Valencia, 46010

Other trials in Spain

United States1 site

  • South Texas Accelerated Research Therapeutics (START)

    San Antonio, Texas, 78229

Other trials in United States

About this study

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

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

Read the 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.

Being tested
Sym004
Keywords
Advanced solid tumors, Metastatic colorectal Cancer
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Sym004Drug

    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.

Study groups in NCT01117428
Study groupRoleWhat they receive
Sym004ExperimentalNot described
Receives: Drug: Sym004

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Adverse Events (AEs)

    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.

    Measured: Visit 2 until first follow-up visit (up to 66 weeks)

Secondary outcomes (3)

  1. Antitumor Activity

    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.

    Measured: Up to 62 weeks

  2. Antitumor Activity Endpoints - Time-to-event Endpoints

    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.

    Measured: Up to 62 weeks

  3. Terminal Half-Life (T½)

    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).

    Measured: See Time Frame in the Outcome Measure Description

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 May 2010 (estimated)
  2. Study startMar 2010
  3. Primary completionFeb 2015
  4. Study completionMay 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
111 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01117428
Sponsor's protocol ID
Sym004-01
Other IDs
2009-017119-13, 2009
Status last verified
Sep 2018
First submitted
23 Apr 2010
Last updated
15 Oct 2018
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 25962717

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Sym004 in people with Metastatic Colorectal Cancer, run by Symphogen A/S at 7 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Belgium, Spain, United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Jul 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Adverse Events (AEs) (time frame: Visit 2 until first follow-up visit (up to 66 weeks)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01117428, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2018.

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Sym004 in Patients With Advanced Solid Tumors | AzTrials