MSC2015103B in Solid Tumors

Advanced Solid Tumor Clinical Trial

Official title:

A Phase I Dose-Escalation First-In-Human Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Oral MEK Inhibitor MSC2015103B Administered With Two Different Treatment Schedules in Subjects With Advanced Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01453387
• Other study ID #: EMR 200064-001
• Status: Completed
• Phase: Phase 1
• First received: September 9, 2011
• Last updated: September 10, 2013
• Start date: September 2011

Study information

• Verified date: September 2013
• Source: EMD Serono
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The main purpose of this study is to test the experimental drug, MSC2015103B at different dose levels and on different treatment schedules, to see whether it is safe and can be tolerated when given to subjects once a day one day per week over a 21-day period or once a day three times per week over a 21-day period. The investigators would also like to find out how MSC2015103B is broken down by the body.

Additional purposes of the trial are to assess side effects of MSC2015103B and to find out whether MSC2015103B has anti-cancer effects. In addition, the investigators would like to explore pharmacokinetics.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Pathologically confirmed solid tumor preferably, but not exclusively, including pancreatic, thyroid, colorectal, non-small cell lung, endometrial, renal, breast, ovarian carcinoma, or melanoma which is locally advanced or metastatic, and either refractory after standard therapy for the disease or for which no effective standard therapy is available.

2. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of = 1.

3. Has read and understands the informed consent form and is willing and able to give informed consent. Fully understands requirements of and willing to comply with all trial visits and assessments.

4. Evidence of measurable disease at trial entry as per Response Evaluation Criteria In Solid Tumors (RECIST) v1.0.

5. Willing to provide archival tissue samples for molecular analysis.

Other inclusion criteria also apply.

Exclusion Criteria:

1. Bone marrow impairment as evidenced by hemoglobin < 9.0 g/dL, neutrophil count < 1.5 x 10^9/L, and/or platelets < 100 x 10^9/L.

2. Renal impairment as evidenced by serum creatinine > 1.5 x ULN (upper limit of normal) and/or calculated creatinine clearance < 50 mL/min (Cockcroft-Gault formula).

3. Liver function and liver cell integrity abnormality as defined by total bilirubin> 1.5 x ULN, or aspartate aminotransferase/alanine aminotransferase (AST/ALT) > 2.5 x ULN, for subjects with liver involvement AST/ALT > 5 x ULN. Subjects with albumin < 2.5 g/dL are also excluded.

4. History of central nervous system (CNS) metastases..

5. History of difficulty of swallowing, malabsorption, or other chronic gastrointestinal disease or conditions that may hamper compliance and/or absorption of the tested product.

6. Chronic diarrhea that is = Grade 2 in severity

7. Clinically significant cardiac conduction abnormalities.

8. A left ventricular ejection fraction of < 45%.

9. A history of stroke or myocardial infarction within the past year.

10. A history of uveitis and scleritis.

11. Retinal pathology beyond normal age-related processes.

12. Evidence of a retinal vein occlusion on fluorescein angiogram or a history of retinal vein occlusion.

Subjects are also excluded if their ophthalmologist finds that their optic disc is at risk for a central retinal vein occlusion.

13. History of glaucoma.

14. Subjects requiring daily and/or chronic systemic steroids.

15. Pregnant or nursing females.

Other exclusion criteria also apply.

Study Design

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

Related Conditions & MeSH terms

• Advanced Solid Tumor

Intervention

Drug:
• MSC2015103B
Once weekly administration schedule: Days 1, 8, and 15 of a 21-day cycle (Schedule 1) dosing will begin at 150 mcg Three times weekly administration schedule: Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle (Schedule 2) dosing will begin at 150 mcg
• MSC2015103B
An Expansion Cohort at the MTD or any other suitable dose level may be utilized to further characterize the safety profile and pharmacodynamics of the drug.

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Karmanos Cancer Institute	Detroit	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
EMD Serono

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of subjects experiencing dose-limiting toxicities (DLT), evaluated over the first cycle of treatment by using the National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI CTCAE) V4.0.		20 months	Yes
Primary	Number of subjects experiencing dose-limiting toxicities (DLT), evaluated over the first cycle of treatment by using the National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI CTCAE) V4.0.		20 months	Yes
Secondary	Proportion of subjects experiencing any treatment emergent adverse event.		20 months	Yes
Secondary	Pharmacokinetic parameters (AUC) of MSC2015103B measured in plasma will be calculated for each cohort using non-compartmental methods.		20 months	No
Secondary	Pharmacokinetic parameters (Cmax) of MSC2015103B measured in plasma will be calculated for each cohort using non-compartmental methods.		20 months	No
Secondary	Pharmacokinetic parameters (tmax) of MSC2015103B measured in plasma will be calculated for each cohort using non-compartmental methods.		20 months	No
Secondary	At the end of the trial MSC2015103B pharmacokinetics (AUC) will be calculated using non-compartmental methods		20 months	No
Secondary	Proportion of subjects experiencing clinically significant changes in a laboratory parameter and /or vital signs judged to be related to the trial medication		20 months	No
Secondary	Proportion of subjects with overall response as defined by confirmed Complete Response (CR) or Partial Response (PR) (using RECIST v1.0) during treatment		20 months	No
Secondary	Proportion of subjects with clinical benefit as defined by confirmed CR, PR or Stable Disease (SD) lasting at least 6 weeks (using RECIST v1.0) during treatment		20 months	No
Secondary	ERK phosphorylation levels will be assessed in peripheral blood mononuclear cells (PBMC) during the dose escalation.		20 months	No
Secondary	Number of subjects experiencing clinically significant changes in a laboratory parameter and /or vital signs judged to be related to the trial medication		20 months	No
Secondary	Number of subjects experiencing any treatment emergent adverse event.		20 months	Yes
Secondary	Number of subjects with overall response as defined by confirmed Complete Response (CR) or Partial Response (PR) (using RECIST v1.0) during treatment		20 months	No
Secondary	Number of subjects with clinical benefit as defined by confirmed CR, PR or Stable Disease (SD) lasting at least 6 weeks (using RECIST v1.0) during treatment		20 months	No