A Clinical Study to evaluate the Safety, Tolerability, and the effects of VX-970 on its own and in combination with Carboplatin on the body in Subjects with Advanced Solid Tumors

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2013-005100-34-GB
• Date of registration: 13/03/2014
• Prospective Registration: Yes
• Primary sponsor: Vertex Pharmaceuticals Incorporated
• Public title: A Clinical Study to evaluate the Safety, Tolerability, and the effects of VX-970 on its own and in combination with Carboplatin on the body in Subjects with Advanced Solid Tumors
• Scientific title: An Open-Label Study of the Safety, Tolerability, and Pharmacokinetic / Pharmacodynamic Profile of VX-970 as a Single Agent in Combination With Carboplatin in Subjects With Advanced Solid Tumors
• Date of first enrolment: 16/04/2014
• Target sample size: 60
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-005100-34
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

United Kingdom

Contacts

• Name: Clincal Trials and Medical Info
• Affiliation: Vertex Pharmaceuticals Incorporated

• Name: Clincal Trials and Medical Info
• Affiliation: Vertex Pharmaceuticals Incorporated

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects who meet all of the following inclusion criteria will be eligible for this study:
1 Male and female subjects =18 years of age
2 Disease status
Parts A1, A2, B1 and B2: Subjects with histologically or cytologically confirmed malignant advanced solid tumors refractory to standard therapy or for which no suitable effective standard therapy exists
a Parts A1 and A2: Subjects will preferentially have mutations known to be involved in the DDR, e.g., ATM or TP53 genes identified by sequencing of tumor tissue derived DNA, using a platform such as the Illumina MiSeq.
b Part B1: In the MTD expansion cohort, at least 6 subjects must have disease sites amenable for paired biopsies
Part C: Subjects must have histologically or cytologically confirmed malignant advanced solid tumors or lymphoma and have tumor genotypes and/or phenotypes of interest based on defects in the DDR, the mechanism of action of VX 970, or on data from ongoing clinical studies
3 Measurable disease according to RECIST criteria (Version 1.1)
4 WHO performance status of 0 or 1
5 Life expectancy of =12 weeks
6 Hematological and biochemical indices within the ranges shown below at Screening. These values must be confirmed at the first day of dosing, before study drug administration
a Hemoglobin: =9.0 g/dL
b Absolute neutrophil count: =2.0 × 109/L
c Platelet count: =150 × 109/L
d Serum bilirubin: =1.5 × upper limit of normal (ULN), unless the subject has known or suspected Gilbert’s syndrome
e Alanine aminotransferase (ALT) and aspartate aminotransferase (AST): =2.5 × (ULN) or =5 × ULN in presence of liver metastases
f Estimated glomerular filtration rate: =50 mL/min
g Prothrombin time: <1.5 × ULN
h In addition, there should not be other clinically significant metabolic or hematologic abnormalities that are uncorrectable or that require ongoing, recurrent pharmacologic management
7 Sign and date an informed consent document
8 Willing and able to comply with scheduled visits, treatment plan, lifestyle, laboratory tests, contraceptive guidelines, and other study procedures

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 60
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60

Exclusion criteria:
Subjects who meet any of the following exclusion criteria are not eligible for this study:
1 Radiotherapy unless brief course for palliative therapy, endocrine therapy (except for ongoing luteinizing hormone releasing hormone agonist therapy for subjects with prostate cancer who have progressed), immunotherapy, or chemotherapy during the 4 weeks (6 weeks for nitrosoureas and Mitomycin C, and 4 weeks for IMP) or 4 drug half lives before first dose of study drug, whichever is greater
2 Ongoing toxic manifestations of previous treatments including known history of Grade 4 thrombocytopenia with any prior chemotherapy regimen, unless approved by the Vertex Medical Monitor. Exceptions to this are alopecia or certain Grade 1 toxicities, which in the opinion of the investigator should not exclude the subject
3 Spinal cord compression or brain metastases unless asymptomatic, treated, stable, and not requiring steroids for at least 4 weeks before first dose of study drug. Any history of leptomeningeal metastases.
4 Female subjects who are already pregnant or lactating, or plan to become pregnant within 6 months of the last dose of study drug are excluded. Female subjects of childbearing potential must adhere to contraception guidelines as outlined in Section 11.6.5.1. Female subjects will be considered to be of nonchildbearing potential if they have undergone surgical hysterectomy or bilateral oophorectomy or have been amenorrheic for over 2 years with a screening serum follicle-stimulating hormone level within the laboratory’s reference range for postmenopausal females
5 Male subjects with partners of childbearing potential must agree to adhere to contraception guidelines in Section 11.6.5.1. Men with pregnant or lactating partners or partners who plan to become pregnant during the study or within 6 months of the last dose of study drug are excluded
6 Major surgery =4 weeks before first dose of study drug, or incomplete recovery from a prior major surgical procedure
7 Cardiac conditions as follows:
a Clinically significant cardiovascular event within 6 months before study entry:
i congestive heart failure requiring therapy
ii unstable angina pectoris
iii myocardial infarction
iv Class II/III/IV cardiac disease
v presence of severe valvular heart disease;
vi presence of a ventricular arrhythmia requiring treatment
b History of arrhythmia that is symptomatic or requires treatment (CTCAE 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Subjects with atrial fibrillation controlled by medication are permitted
c Uncontrolled hypertension (blood pressure =160/100 despite optimal therapy)
d Second or third degree heart block with or without symptoms
e QTc >470 msec not due to electrolyte abnormality and that does not resolve with correction of electrolytes
f History of congenital long QT syndrome
g History of torsades de pointes (or concurrent medication with a known risk of inducing torsades de pointes)
h Clinically-significant abnormality, including ejection fraction below normal institutional limits, present on transthoracic echocar

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Cancer (malignant solid tumors)
MedDRA version: 19.0 Level: LLT Classification code 10065147 Term: Malignant solid tumor System Organ Class: 100000004864

Intervention(s)

Product Name: VX-970
Product Code: VRT-0768079
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Not yet available
Current Sponsor code: VX-970
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: range
Concentration number: 5-20

Product Name: Carboplatin
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Carboplatin
CAS Number: 41575-94-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Trade Name: Paclitaxel 6mg/ml concentrate for solution for infusion
Product Name: Paclitaxel
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: PACLITAXEL
CAS Number: 33069-62-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 6-

Primary Outcome(s)

Main Objective: PART A
To determine the maximum tolerated dose (MTD) and evaluate the safety and tolerability of multiple ascending doses of VX 970 administered once weekly (Part A1) or twice weekly (Part A2) as a single agent in subjects with advanced solid tumors

PART B
To determine the maximum tolerated dose and evaluate the safety and tolerability of VX 970 when administered in combination with carboplatin (Part B1) and with carboplatin and paclitaxel (Part B2) in subjects with advanced solid tumors

PART C
To evaluate the safety and tolerability of VX 970 administered as a single agent followed by administration of VX 970 in combination with carboplatin in subjects with solid tumors and lymphoma with tumor genotypes and/or phenotypes of interest based on defects in the DDR, the mechanism of action of VX 970, and on data from ongoing clinical studies

Secondary Objective: PART A
- Evaluate PK of VX-970 when administered as a single agent
- Assess potential antitumour responses after administration of VX-970
PART B
- Evaluate PK of VX-970 when administered in combination with carboplatin (part B1) and with carboplatin and paclitaxel (Part B2)
- Assess potential antitumour responses after administration of VX-970 in combination with carboplatin (part B1) and with carboplatin and paclitaxel (Part B2)
- Assess response duration after administration of VX-970 in combination with carboplatin (part B1) and with carboplatin and paclitaxel (Part B2)
PART C
- Assess antitumour responses after administration of VX-970 as a single agent and in combination with carboplatin
- Evaluate PK of VX-970 when administered as a single agent and in combination with carboplatin
- Assess response duration after administration of VX-970 as a single agent and in combination with carboplatin

Timepoint(s) of evaluation of this end point: Evaluated continuously during dosing until 14 days after dosing.

Primary end point(s): Parts A:
- Safety parameters, including AEs, clinical laboratory values (serum chemistry and hematology), vital signs, and ECG assessments
-MTD of VX 970 administered once weekly (Part A1) or twice weekly (Part A2) as a single agent
Parts B:
- Safety parameters, including AEs, clinical laboratory values (serum chemistry and hematology), vital signs, and ECG assessments
-MTD of VX 970 administered in combination with carboplatin (Part B1) and with carboplatin and paclitaxel (Part B2)
Part C:
Safety parameters, including AEs, clinical laboratory values (serum chemistry and hematology), vital signs, and ECG

Secondary Outcome(s)

Secondary end point(s): PART A:
- PK parameter estimates of VX 970, administered once weekly (Part A1) or twice weekly (Part A2) as a single agent, derived from plasma concentration time data
-Objective tumor response (OR) as evaluated by Response Criteria Evaluation (Response Evaluation Criteria in Solid Tumors [RECIST]) 1.1 and tumor markers

PART B
-PK parameter estimates of VX 970, administered in combination with carboplatin (Part B1) and with carboplatin and paclitaxel (Part B2), derived from plasma concentration time data
-OR as evaluated by Response Criteria Evaluation (RECIST) 1.1 and tumor markers
-Response duration as evaluated by Response Criteria Evaluation RECIST 1.1 and tumor markers
PART C
-OR as evaluated by Response Criteria Evaluation RECIST 1.1 and tumor markers
-PK parameter estimates of VX 970, administered as a single agent and in combination with carboplatin, derived from plasma concentration time data
-Response duration as evaluated by Response Criteria Evaluation RECIST 1.1 and tumor markers

Timepoint(s) of evaluation of this end point: See section 11 of the protocol

Secondary ID(s)

VX13-970-002

Source(s) of Monetary Support

Vertex Pharmaceuticals Incorporated

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 26/01/2019
• Date Completed: 10/01/2018
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-005100-34/results