First-in-Human Study of the Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Profile of VX-984 in Combination With Chemotherapy

NCT ID: NCT02644278

Last Updated: 2019-09-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-29
• Study Completion Date: 2017-10-19

Brief Summary

The purpose of this study was to evaluate the safety and tolerability of VX-984 (M9831) administered alone and in combination with pegylated liposomal doxorubicin (PLD), and to determine the maximum tolerated dose (MTD) and preliminary evidence of efficacy of VX-984 in combination with PLD in participants with advanced solid tumors.

Conditions

Advanced Solid Tumor

Study Design

• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

VX-984 120 mg + PLD 40 mg/m^2

Group Type: EXPERIMENTAL

VX-984 120 mg + PLD 40 mg/m^2

Intervention Type: DRUG

Participants received VX-984 orally 120 milligram (mg) orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 120 mg in combination with pegylated liposomal doxorubicin (PLD) 40 milligram per square meter (mg/m\^2) administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.

VX-984 240 mg + PLD 40 mg/m^2

Group Type: EXPERIMENTAL

VX-984 240 mg + PLD 40 mg/m^2

Intervention Type: DRUG

Participants received VX-984 orally 240 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 240 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.

VX-984 480 mg + PLD 40 mg/m^2

Group Type: EXPERIMENTAL

VX-984 480 mg + PLD 40 mg/m^2

Intervention Type: DRUG

Participants received VX-984 orally 480 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 480 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.

VX-984 720 mg + PLD 40 mg/m^2

Group Type: EXPERIMENTAL

VX-984 720 mg + PLD 40 mg/m^2

Intervention Type: DRUG

Participants received VX-984 orally 720 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 720 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.

Interventions

VX-984 120 mg + PLD 40 mg/m^2

Participants received VX-984 orally 120 milligram (mg) orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 120 mg in combination with pegylated liposomal doxorubicin (PLD) 40 milligram per square meter (mg/m\^2) administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.

Intervention Type: DRUG

VX-984 240 mg + PLD 40 mg/m^2

Participants received VX-984 orally 240 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 240 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.

Intervention Type: DRUG

VX-984 480 mg + PLD 40 mg/m^2

Participants received VX-984 orally 480 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 480 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.

Intervention Type: DRUG

VX-984 720 mg + PLD 40 mg/m^2

Participants received VX-984 orally 720 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 720 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.

Intervention Type: DRUG

Other Intervention Names

M9831

Eligibility Criteria

Inclusion Criteria

• Participants (male and female for Part A and female for Part B) were at least 18 year of age.
• Part A Participants with histologically or cytologically confirmed malignant advanced solid tumors, who had progressed on at least 1 prior chemotherapy, and for whom either

1. No standard care available

2. PLD at the dose and schedule being used might be considered standard of care

• Part B

1. Participants with histologically confirmed advanced primary endometrial cancer (locally advanced and incurable endometrial cancer that had been treated with surgery and/or radiation or is ineligible for such treatment), or recurrent or metastatic endometrial cancer, and

2. Completed 1 line of chemotherapy treatment with a platinum-containing regimen in the advanced setting

• Measurable disease according to RECIST criteria (Version 1.1)
• Life expectancy of at least 12 weeks
• Hematological and biochemical indices within acceptable ranges shown at screening.
• Normal left ventricular ejection fraction on screening assessed by transthoracic echocardiogram or multiple gated acquisition (MUGA) scan

Exclusion Criteria

• Previous radiotherapy (unless brachytherapy), endocrine therapy, chemotherapy, or exposure to investigational medicinal products during the 4 weeks (6 weeks for nitrosoureas and Mitomycin-C) or 4 drug half-lives before the planned administration of the first dose of study drug, whichever is greater. Previous immunotherapy during the 4 weeks before the planned administration of the first dose of study drug.
• For Part B only:

1. Participants with uterine carcinosarcoma

2. Prior anthracycline therapy

3. More than 1 prior chemotherapy regimen (a participant was received first- line carboplatin and taxane and then received the same taxane second- line were considered to have had 1 prior chemotherapy regimen)

• Unresolved toxicity of Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or greater from previous anti-cancer therapy or radiotherapy
• History of spinal cord compression or brain metastases, unless asymptomatic, treated, stable, and not requiring treatment with steroids for at least 4 weeks before the planned administration of the first dose of study drug. Any history of leptomeningeal metastases.
• Female participants who was pregnant or lactating at Screening, or planned to become pregnant while on study or within 6 months after the last dose of study drug
• Female participants of childbearing potential were adhere to contraception guidelines as outlined in the protocol. Female participants were considered to be of nonchildbearing potential if they had undergone surgical hysterectomy or bilateral oophorectomy or had been amenorrheic for more than 2 years with a screening serum follicle-stimulating hormone (FSH) level within the laboratory's reference range for postmenopausal females
• Male participants with pregnant or lactating partners or partners who planned to become pregnant while on study or within 6 months after the planned administration of the last dose of study drug
• Major surgery ≤4 weeks before first dose of study drug, or incomplete recovery from a prior major surgical procedure
• Cardiac conditions
• Prior bone marrow transplant
• Extensive radiotherapy (to greater than 15% of bone marrow)
• Any other condition that in the investigator's opinion would not make the participant a good candidate for the clinical study,
• Part B: Current active malignancies of other types, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin. Prior cancer in remission for 2 years or more would not be excluded.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: collaborator

EMD Serono Research & Development Institute, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Responsible

Role: STUDY_DIRECTOR

EMD Serono Research & Development Institute, Inc., a subsidiary of Merck KGaA, Darmstadt, Germany

Locations

Scottsdale, Arizona, United States

Boston, Massachusetts, United States

Nashville, Tennessee, United States

Dallas, Texas, United States

Houston, Texas, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

VX15-984-001

Identifier Type: OTHER

Identifier Source: secondary_id

MS201926-0001

Identifier Type: -

Identifier Source: org_study_id