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Phase I Dose Escalation Trial of MEK1/2 Inhibitor MSC1936369B Combined With Temsirolimus in Subjects With Advanced Solid Tumors


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Advanced Solid Tumor

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Trial Information

Phase I Dose Escalation Trial of MEK1/2 Inhibitor MSC1936369B Combined With Temsirolimus in Subjects With Advanced Solid Tumors


Inclusion Criteria:



1. Subjects with histologically or cytologically confirmed solid tumors, either
refractory to standard therapy or for which no effective standard therapy is
available.

2. Measurable or evaluable disease at baseline by RECIST 1.0.

3. Age ≥ 18 years.

4. Subject has read and understands the informed consent form and is willing and able to
give informed consent.

5. Performance Status score of ≤ 1 according to the Eastern Cooperative Oncology Group
(ECOG) scale.

6. Women of childbearing potential must have a negative blood pregnancy test at the
screening visit.

7. Female subjects of childbearing potential and male subjects with female partners of
childbearing potential must be willing to avoid pregnancy by using an adequate method
of contraception for 2 weeks prior to screening, during the trial and for 3 months
after the last dose of trial medication.

Additional inclusion criteria also apply.

Exclusion Criteria:

1. The subject has previously been treated with an mTOR inhibitor or a MEK inhibitor and
taken off treatment due to drug-related adverse events.

2. The subject has received any of the following:

- Chemotherapy, immunotherapy, hormonal therapy, biologic therapy, any
investigational agent or any other anti-cancer therapy within 28 days (6 weeks
for nitrosoureas or mitomycin C) of Day 1 of trial treatment; non-cytotoxic
chemotherapy or investigational agent with limited potential for delayed
toxicity is permitted if terminated at least 5 halflives prior to Day 1 of trial
treatment.

- Extensive prior radiotherapy on more than 30% of bone marrow reserves, or prior
bone marrow/stem cell transplantation.

3. The subject has not recovered from toxicity due to prior therapy to baseline or
Common Terminology Criteria for Adverse Events (CTCAE v4.0) of Grade 1 or less
(except alopecia).

4. The subject has poor organ or marrow function

5. History of CNS metastases or primary CNS tumor, unless subject has been previously
treated for these conditions, is asymptomatic and has had no requirement for
anticonvulsants or high dose corticosteroids for a minimum of 2 weeks prior to entry
into the trial.

6. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 6 months of Day 1 of trial drug treatment.

7. Recent major surgery or trauma (within the last 28 days), unhealing/open wounds,
diabetic ulcers, recent drainage of significant volume of ascites or pleural
effusion.

8. History of congestive heart failure, unstable angina, myocardial infarction,
symptomatic cardiac conduction abnormality, pacemaker, or other clinically
significant cardiac disease or history of a stroke within 3 months prior to entering
the trial.

9. Baseline corrected QT interval on screening electrocardiogram (ECG) (QTc) ≥ 460 ms or
left ventricular ejection fraction (LVEF) < 40% on screening echocardiogram.

10. Other uncontrolled intercurrent diseases

11. Retinal degenerative disease (hereditary retinal degeneration or age-related macular
degeneration), history of uveitis or history of retinal vein occlusion, or medically
relevant abnormal ophthalmology assessments at screening.

12. Known or suspected allergy to MSC1936369B, temsirolimus, other rapamycins (sirolimus,
everolimus, etc.), their excipients, or any agent given in the course of this trial.

13. Immunization with attenuated live vaccines within one week of trial entry (examples
of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio,
BCG, etc.).

14. Concomitant use of any medications or substances that are strong inhibitors or
inducers of CYP3A enzyme, including, but not limited to, phenytoin, carbamazepine,
barbiturates, azoles, rifampin, phenobarbital, or St. John's Wort.

15. Pregnant or lactating female.

16. Legal incapacity or limited legal capacity.

Additional exclusion criteria also apply.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of Dose Limiting Toxicities

Outcome Description:

DLTs are any of the following toxicities observed within first cycle of treatment and judged not to be related to underlying disease or concomitant medications: Any Grade ≥ 3 non-hematological toxicity with certain exceptions Grade 4 neutropenia of > 5 days or or febrile neutropenia of > 1 day Grade 3 thrombocytopenia with bleeding or grade 4 thrombocytopenia Any treatment interruption > 2 weeks due to AEs not related to the underlying disease or concomitant medication Any severe or life-threatening condition not defined in the NCI-CTCAE that is attributable to the therapy

Outcome Time Frame:

21 months

Safety Issue:

No

Principal Investigator

Lars Damstrup, MD, PhD,

Investigator Role:

Study Director

Investigator Affiliation:

Merck KGaA

Authority:

United States: Food and Drug Administration

Study ID:

EMR 200066-005

NCT ID:

NCT01378377

Start Date:

June 2011

Completion Date:

Related Keywords:

  • Advanced Solid Tumor
  • MEK inhibitor
  • Temsirolimus
  • Solid Tumor
  • Phase I
  • Pimasertib
  • Neoplasms

Name

Location

Cedars-Sinai Medical CenterLos Angeles, California  90048
The University of Texas MD Anderson Cancer CenterHouston, Texas  77030-4009
For Recruiting Locations in the US contact US Medical Information inRockland, Massachusetts