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Advanced Solid TumorsPhase 1/2NCT01226056

Sorafenib in Combination With RAD001 in Advanced Solid Tumors Selected on Molecular Targets

A Phase 1/2 study testing RAD001 in combination with sorafenib in people with Advanced Solid Tumors, run by Southern Europe New Drug Organization at 1 site in Italy.

Suspended

Paused. Enrolment is on hold for now and may resume.

Official record
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Trial summary

Sorafenib is an oral multikinase inhibitor and among its targets are several RTKs involved in tumor genesis (Raf, Flt-3, c-Kit and RET) and angiogenesis (VEGFR1, 2 and 3 and PDGFRß). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Solid Tumors
What is being tested?
RAD001 in combination with sorafenib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
45 participants
Where
1 siteItaly
Study dates
Mar 2009to Dec 2012
Phase
Phase 1/2
Are there results?
None posted in the registry

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

  • Patients with progressive disease of advanced solid tumours judged non suitable for standard treatment
  • Biopsiable lesion or archive tissue not older than 1 year to assess the expression of:
  • phosphorylated AKT
  • phosphorylated p70S6
  • RKIP (Raf Kinase Inhibitor Protein)
  • phosphorylated ERK1/2 The presence of at least one of the previous targets will be mandatory for patient enrolment
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  • At least 1 uni-dimensional measurable lesion according to modified RECIST
  • Life expectancy of at least 12 weeks
  • Age ≥ 18 years old
  • ECOG Performance Status of 0 or 1
  • Adequate bone marrow, liver, and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to start of first dose:
  • Haemoglobin ≥9.0 g/dL (5.6 mmol/L)
  • Absolute neutrophil count (ANC)≥1.5 x 109/L
  • Platelet count ≥100 x 109/L
  • Total bilirubin ≤1.5 x upper limit of normal (ULN)
  • ALT and AST ≤2.5 x ULN (≤5 x ULN for patients with liver involvement of their cancer)
  • Alkaline phosphatase ≤4 x ULN
  • PT-INR/PTT <1.5 x ULN
  • Serum albumin levels ≥2.5 mg/dl
  • Serum creatinine ≤1.5 x ULN
  • HBV/HCV testing in the 2 weeks before treatment start in specific categories of patient with hepatitis B and C risk factors and in additional patients at the discretion of the investigators according to guidelines in Appendix 6.
  • All fertile patients must use adequate contraception while on study and for three subsequent months
  • Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to performing any study specific procedures

Who cannot join

  • History of cardiac disease: congestive heart failure (NYHA II-IV), active coronary artery disease - CAD (MI more than 6 months prior to study entry is allowed), cardiac arrhythmias requiring antiarrhythmic therapy (betablockers or digoxin are permitted) or uncontrolled hypertension
  • History of HIV infection or chronic hepatitis B or C
  • Patients with NSCLC squamous histotype
  • Recurrent hemoptysis or cerebrovascular accident within 12 months, or peripheral vascular disease with claudication on less than 1 block (about 150 metres), or history of clinically significant bleeding non-traumatic
  • Deep venous thrombosis or pulmonary embolus within 1 year or ongoing need for full-dose oral or parenteral anticoagulation
  • Clinically active infections (> Grade 2 NCI-CTC AE version 3.0)
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  • Evidence of CNS tumor metastases
  • History of organ allograft
  • Pre-existing thyroid abnormality where thyroid function cannot be maintained in the normal range by medication
  • Serious, non-healing wound, ulcer, or bone fracture
  • Second malignancies within the past 5 years (except for non - melanoma skin cancer and cervical carcinoma in situ)
  • Pregnant or breast-feeding patients
  • Substance abuse, medical, psychological, or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
  • Any condition that is unstable or could jeopardize the safety of the patient and his/her compliance in the study
  • Patients unable to swallow oral medications
  • Any malabsorption condition
  • Prior treatment with sorafenib or m-TOR inhibitors
  • Ongoing requirement for systemic corticosteroid medication or other immunosuppressants
  • Radiotherapy within 3 weeks of start of study drug. Palliative radiotherapy is allowed. Major surgery within 4 weeks of study entry
  • Radiotherapy involving > 30% of the active bone marrow
  • Autologous bone marrow transplant or stem cell rescue within 4 months of study entry
  • Use of biologic response modifiers, such as G-CSF, within 3 week of study entry. Patients taking chronic erythropoietin are permitted provided no dose adjustment is undertaken within 2 months prior to the study or planned during the study period
  • Investigational drug therapy outside of this trial during or within 4 weeks of study entry

Trial locations and contacts

1 site in 1 country.

Italy1 site

  • Istituto Europeo di Oncologia,

    Milan, 20141

Other trials in Italy

About this study

Official title: Phase I/II Trial With Sorafenib in Combination With RAD001 Administered Orally in Patients With Advanced Solid Tumors, Selected on the Base of Molecular Targets

Sorafenib is an oral multikinase inhibitor and among its targets are several RTKs involved in tumor genesis (Raf, Flt-3, c-Kit and RET) and angiogenesis (VEGFR1, 2 and 3 and PDGFRß). Therefore sorafenib inhibits tumor growth by a dual mechanism, acting either directly on the tumor (through inhibition of Raf and Kit signaling) and/or on tumor angiogenesis (through inhibition of VEGFR and PDGFR signaling.

RAD001 is a novel derivative of rapamycin. It selectively inhibits mTOR directly blocking tumor cells by preventing tumor cell growth and proliferation and indirectly by inhibiting angiogenesis (via potent inhibition of the HIF-1 and consequently VEGF production).

Read more

Targeting mTOR in combination with sorafenib might lead to more profound effects on tumor cell biology than could be achieved through individual targeting of some proteins.

New drugs have often met only limited success since not always target pathways responsible for tumor development and growth are targeted. To overcome this problem, the specific pathways targeted by the investigators two drugs will be analyzed in each single patient before the inclusion.

Being tested
RAD001 in combination with sorafenib
Keywords
advanced solid tumors, Sorafenib (Nexavar®), RAD001 (everolimus), tumor molecular targets

What participants receive

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

  • RAD001 in combination with sorafenibDrug

    Also called RAD001 (Everolimus), Sorafenib (Nexavar®)

    Phase I / Dose escalation: during the first cycle RAD001 (2.5-10 mg/day) will be administered alone, once a day, on days 1-14 to allow PK-profiling of the drug. From day 15 sorafenib administration (400-800 mg/day) twice a day will be added.

    The cycle 1 will last 6 weeks, subsequent cycles will last 4 weeks (the 2 drugs administered in combination from day 1 to day 28).

    Phase II: The drugs will be administered at the Recommended Dose and each treatment cycle will last 4 weeks.

Study groups in NCT01226056
Study groupRoleWhat they receive
RAD001 in combination with sorafenibExperimentalNot described
Receives: Drug: RAD001 in combination with sorafenib

What is being measured

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

  1. Phase I: Maximum Tolerated Dose (MTD)

    The maximum tolerated dose (MTD) is defined as the dose in which 2 of 3 or 2 of 6 patients experience a DLT. The Recommended Dose is identified as one dose level below the MTD.

    Measured: 6 weeks

  2. Phase II: PFS (Progression Free survival) rate

    Measured: 3 months

Secondary outcomes (5)

  1. Phase I: Pharmacokinetics profile of both drugs

    Measured: 6 weeks

  2. Phase II: overall survival

    Measured: 15 months

  3. Tumor response

    Evaluated according to RECIST criteria

    Measured: every 8 weeks

  4. Objective Response Rate (ORR)

    Measured: 15 months

  5. Incidence and severity of AEs

    graded according to CTCAE criteria v3.0

    Measured: 36 months

Timeline

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

  1. First posted21 Oct 2010 (estimated)
  2. Study startMar 2009
  3. Primary completionSep 2012 (estimated)
  4. Study completionDec 2012 (estimated)

Why it stopped: toxicity (protocol amendment under approval)

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
45 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01226056
Sponsor's protocol ID
S075SORD01
Status last verified
Oct 2010
First submitted
18 Oct 2010
Last updated
21 Oct 2010
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing RAD001 in combination with sorafenib in people with Advanced Solid Tumors, run by Southern Europe New Drug Organization at 1 site in Italy.

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 23 inclusion and 23 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: paused, as of the sponsor's last update on 21 Oct 2010. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. 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?

Results are not available in the source record.

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?

Phase I: Maximum Tolerated Dose (MTD) (time frame: 6 weeks). The study lists 2 primary outcomes in all. 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 NCT01226056.

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 21 Oct 2010.

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