Clinical Trials Logo

Clinical Trial Details — Status: Suspended

Administrative data

NCT number NCT01226056
Other study ID # S075SORD01
Secondary ID
Status Suspended
Phase Phase 1/Phase 2
First received October 18, 2010
Last updated October 20, 2010
Start date March 2009
Est. completion date December 2012

Study information

Verified date October 2010
Source Southern Europe New Drug Organization
Contact n/a
Is FDA regulated No
Health authority Italy: Istituto Superiore di Sanità
Study type Interventional

Clinical 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). 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).

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.


Recruitment information / eligibility

Status Suspended
Enrollment 45
Est. completion date December 2012
Est. primary completion date September 2012
Accepts healthy volunteers No
Gender Both
Age group 18 Years and older
Eligibility Inclusion Criteria:

1. Patients with progressive disease of advanced solid tumours judged non suitable for standard treatment

2. 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

3. At least 1 uni-dimensional measurable lesion according to modified RECIST

4. Life expectancy of at least 12 weeks

5. Age = 18 years old

6. ECOG Performance Status of 0 or 1

7. 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

8. 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.

9. All fertile patients must use adequate contraception while on study and for three subsequent months

10. 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

Exclusion Criteria:

1. 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

2. History of HIV infection or chronic hepatitis B or C

3. Patients with NSCLC squamous histotype

4. 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

5. Deep venous thrombosis or pulmonary embolus within 1 year or ongoing need for full-dose oral or parenteral anticoagulation

6. Clinically active infections (> Grade 2 NCI-CTC AE version 3.0)

7. Evidence of CNS tumor metastases

8. History of organ allograft

9. Pre-existing thyroid abnormality where thyroid function cannot be maintained in the normal range by medication

10. Serious, non-healing wound, ulcer, or bone fracture

11. Second malignancies within the past 5 years (except for non - melanoma skin cancer and cervical carcinoma in situ)

12. Pregnant or breast-feeding patients

13. Substance abuse, medical, psychological, or social conditions that may interfere with the patient's participation in the study or evaluation of the study results

14. Any condition that is unstable or could jeopardize the safety of the patient and his/her compliance in the study

15. Patients unable to swallow oral medications

16. Any malabsorption condition

17. Prior treatment with sorafenib or m-TOR inhibitors

18. Ongoing requirement for systemic corticosteroid medication or other immunosuppressants

19. Radiotherapy within 3 weeks of start of study drug. Palliative radiotherapy is allowed. Major surgery within 4 weeks of study entry

20. Radiotherapy involving > 30% of the active bone marrow

21. Autologous bone marrow transplant or stem cell rescue within 4 months of study entry

22. 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

23. Investigational drug therapy outside of this trial during or within 4 weeks of study entry

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms


Intervention

Drug:
RAD001 in combination with sorafenib
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.

Locations

Country Name City State
Italy Istituto Europeo di Oncologia, Milano

Sponsors (3)

Lead Sponsor Collaborator
Southern Europe New Drug Organization Bayer, Novartis

Country where clinical trial is conducted

Italy, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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. 6 weeks Yes
Primary Phase II: PFS (Progression Free survival) rate 3 months No
Secondary Phase I: Pharmacokinetics profile of both drugs 6 weeks Yes
Secondary Phase II: overall survival 15 months No
Secondary Tumor response Evaluated according to RECIST criteria every 8 weeks No
Secondary Objective Response Rate (ORR) 15 months No
Secondary Incidence and severity of AEs graded according to CTCAE criteria v3.0 36 months Yes
See also
  Status Clinical Trial Phase
Active, not recruiting NCT04972981 - A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of ADCT-901 in Participants With Selected Advanced Solid Tumors Phase 1
Completed NCT05086822 - A Study of Irinotecan Hydrochloride Liposome in Advanced Solid Tumors Phase 1
Completed NCT03260322 - A Multiple-dose Study of ASP8374, an Immune Checkpoint Inhibitor, as a Single Agent and in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors Phase 1
Completed NCT02526017 - Study of Cabiralizumab in Combination With Nivolumab in Patients With Selected Advanced Cancers Phase 1
Recruiting NCT06040541 - Study of RMC-9805 in Participants With KRASG12D-Mutant Solid Tumors Phase 1
Recruiting NCT05862831 - Clinical Study of PM1003 in Phase I/IIa Treatment of Advanced Malignant Solid Tumors Phase 1/Phase 2
Recruiting NCT03641794 - Indoleamine 2,3-Dioxygenase (IDO) Inhibitor in Healthy Volunteers Phase 1
Terminated NCT03665129 - IPH5401 (Anti-C5aR) in Combination With Durvalumab in Patients With Advanced Solid Tumors Phase 1
Not yet recruiting NCT06413680 - A First-In Human (FIH) Trial to Find Out if REGN10597 is Safe and How Well it Works for Adult Participants With Advanced Solid Organ Malignancies Phase 1/Phase 2
Recruiting NCT05914116 - A Study of DB-1311 in Advanced/Metastatic Solid Tumors Phase 1/Phase 2
Completed NCT01693562 - A Phase 1/2 Study to Evaluate MEDI4736 Phase 1/Phase 2
Recruiting NCT04387916 - A Study of KC1036 in Patients With Advanced Solid Tumors Phase 1
Completed NCT04095273 - Study to Test How Well Patients With Advanced Solid Tumors Respond to Treatment With the Elimusertib in Combination With Pembrolizumab, to Find the Optimal Dose for Patients, How the Drug is Tolerated and the Way the Body Absorbs, Distributes and Discharges the Drug Phase 1
Not yet recruiting NCT03692520 - Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of SCT200 in Patients With Advanced Solid Tumors Phase 1
Completed NCT02997176 - An Open-Label Pharmacokinetics and Safety Study of Talazoparib (MDV3800) Phase 1
Recruiting NCT04446260 - A Study of SHR-A1811 in Subjects With Advanced Malignant Solid Tumors Phase 1
Recruiting NCT06239155 - A Phase I/II Study of AST-3424 in Subjects With Advanced Solid Tumors Phase 1/Phase 2
Terminated NCT02253992 - An Investigational Immuno-therapy Study to Determine the Safety of Urelumab Given in Combination With Nivolumab in Solid Tumors and B-cell Non-Hodgkin's Lymphoma Phase 1/Phase 2
Recruiting NCT06076291 - An Open-label Study of SG1827 in Subjects With Advanced Solid Tumors Phase 1
Completed NCT03545971 - A Study of IBI310 for the Treatment of Patients With Advanced Solid Tumors. Phase 1