MSC2015103B in Solid Tumors

NCT01453387 | Terminated Phase 1 Results

• 1 other identifier: EMR 200064-001
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Advanced Solid Tumor

Keywords

MEK inhibitor; Solid Tumor; Phase I

Outcome Measures

Primary Outcomes (2)

• Number of Subjects Who Experienced Dose-limiting Toxicities (DLT)

  DLT was evaluated using the National cancer institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. DLT was defined as any of the following AEs occurring during Cycle 1 that are not related to progressive disease (PD) at any dose level: Any Grade 3 or more non-hematological toxicity excluding: Grade 3 diarrhea or associated electrolyte abnormalities that were controlled with adequate and optimal therapies, Grade 3 liver function abnormalities which resolved within 7 days, vomiting. Grade 4 neutropenia of greater than (\>) 5 days duration or Grade 3 febrile neutropenia, Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding, any severe or life threatening AE or any AE or abnormality which impairs daily normal physiological functions, any treatment delay for 2 weeks or more due to adverse effects not related to PD. All events judged to be related by the Investigator to PD were excluded from the DLT definition.

  Up to Day 21 of Cycle 1

• Percentage of Subjects Who Experienced DLT

  DLT was evaluated using the National cancer institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. DLT was defined as any of the following AEs occurring during Cycle 1 that are not related to PD at any dose level: Any Grade 3 or more non-hematological toxicity excluding: Grade 3 diarrhea or associated electrolyte abnormalities that were controlled with adequate and optimal therapies, Grade 3 liver function abnormalities which resolved within 7 days, vomiting. Grade 4 neutropenia of greater than (\>) 5 days duration or Grade 3 febrile neutropenia, Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding, any severe or life threatening AE or any AE or abnormality which impairs daily normal physiological functions, any treatment delay for 2 weeks or more due to adverse effects not related to PD. All events judged to be related by the Investigator to PD were excluded from the DLT definition.

  Up to Day 21 of Cycle 1

Secondary Outcomes (13)

• Percentage of Subjects Who Experienced Any Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation

  From the initiation of the trial till the data cut-off date 15 July 2013

• Percentage of Subjects Who Experienced Clinically Significant Lab Abnormality Judged to be Related to the Trial Medication

  From the initiation of the trial till the data cut-off date 15 July 2013

• Number of Subjects Who Experienced Clinically Significant Lab Abnormality Judged to be Related to the Trial Medication

  From the initiation of the trial till the data cut-off date 15 July 2013

• Maximum Plasma Concentration (Cmax)

  Schedule 1 : 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, 24.0, 48 or 72, 72 or 96 and 168 hours post-dose during Week 1 and Week 3; Schedule 2: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, and 24.0 hours post-dose on Days 1 and 17.

• Time to Reach Maximum Plasma Concentration (Tmax)

  Schedule 1: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, 24.0, 48 or 72, 72 or 96 and 168 hours post-dose during Week 1 and Week 3; Schedule 2: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, and 24.0 hours post-dose on Day 1 and 17.

Study Arms (2)

Part 1 - MSC2015103B (Schedule 1)

EXPERIMENTAL

Drug: MSC2015103B

Part 1 - MSC2015103B (Schedule 2)

EXPERIMENTAL

Drug: MSC2015103B

Interventions

MSC2015103B DRUG

Schedule 1: MSC2015103B will be administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle until MTD establishment. Starting dose will be 150 microgram (mcg), which will be escalated to 200 mcg, 300 mcg, 450 mcg, 650 mcg, 1000 mcg and 1500 mcg subsequently.

Part 1 - MSC2015103B (Schedule 1)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of less than or equal to (\<=) 1
• 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
• Evidence of measurable disease at trial entry as per Response Evaluation Criteria In Solid Tumors (RECIST) v1.0.
• Willing to provide archival tissue samples for molecular analysis

You may not qualify if:

• Bone marrow impairment as evidenced by hemoglobin less than (\<) 9.0 gram per deciliter (g/dL), neutrophil count \< 1.5 x 10\^9 per liter (/L), and/or platelets \<100 x 10\^9/L per liter (/L)
• Renal impairment as evidenced by serum creatinine greater than (\>) 1.5 x upper limit of normal (ULN) and/or calculated creatinine clearance \< 50 milliliter per minute (mL/min) (Cockcroft-Gault formula)
• 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
• History of central nervous system (CNS) metastases.
• History of difficulty of swallowing, malabsorption, or other chronic gastrointestinal disease or conditions that may hamper compliance and/or absorption of the tested product.
• Chronic diarrhea that is \>= Grade 2 in severity
• Clinically significant cardiac conduction abnormalities
• A left ventricular ejection fraction of \< 45%
• A history of stroke or myocardial infarction within the past year
• A history of uveitis and scleritis
• Retinal pathology beyond normal age-related processes
• 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
• History of glaucoma
• Subjects requiring daily and/or chronic systemic steroids

Sponsors & Collaborators

• EMD Serono: lead

Study Sites (3)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, United States

Location

Limitations and Caveats

The study was terminated early during Part 1 of the trial due to administrative reason. Pharmacodynamics evaluations were not performed due to early termination.

Results Point of Contact

• Title: Merck KGaA Communication Center
• Organization: Merck Serono, a division of Merck KGaA

service@merckgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  Merck Serono, a division of Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2011
• First Posted: October 17, 2011
• Study Start: September 1, 2011
• Primary Completion: July 1, 2013
• Study Completion: July 1, 2013
• Last Updated: May 8, 2017
• Results First Posted: May 8, 2017

Record last verified: 2017-03

Locations

US (3)