An Open-Label, First-in-Human Study of the Safety, Tolerability, and Pharmacokinetics of VX-970 in Combination With Cytotoxic Chemotherapy

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2015 by Vertex Pharmaceuticals Incorporated
Sponsor:
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:
NCT02157792
First received: June 1, 2014
Last updated: October 15, 2015
Last verified: October 2015
  Purpose
An Open-Label, First-in-Human Study of the Safety, Tolerability, and Pharmacokinetics (PK) of VX-970 in Combination With Cytotoxic Chemotherapy in Subjects With Advanced Solid Tumors

Condition Intervention Phase
Advanced Solid Tumor
Drug: VX-970
Drug: gemcitabine
Drug: cisplatin
Drug: etoposide
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, First-in-Human Study of the Safety, Tolerability, and Pharmacokinetics of VX-970 in Combination With Cytotoxic Chemotherapy in Subjects With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by Vertex Pharmaceuticals Incorporated:

Primary Outcome Measures:
  • Parts A, B, C1, C2: Safety parameters, including adverse event (AEs), clinical laboratory values (serum chemistry, hematology, and urinalysis), vital signs, and electrocardiogram (ECG) assessments [ Time Frame: Screening through Safety Follow-up (approximately 22 weeks) ] [ Designated as safety issue: Yes ]
  • Parts C1 and C2: Overall Response Rate (ORR) for all subjects in Part C1 (advanced non-small cell lung cancer) and ORR for subjects in Part C2 who are basaloid subtype, BRCA1/BRCA2 germline wild-type (triple negative breast cancer), [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Part A: Maximum tolerated dose (MTD) of VX-970 administered in combination with cisplatin and gemcitabine and in combination with gemcitabine [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Part A: Pharmacokinetic (PK) parameter estimates of VX-970 in combination with cisplatin and gemcitabine and in combination with gemcitabine [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Part B: Maximum tolerated dose (MTD) of VX-970 administered in combination with gemcitabine and cisplatin in combination with gemcitabine [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Part B: PK parameter estimates of VX-970 in combination with cisplatin and in combination with cisplatin and etoposide [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Part B: PK parameter estimates of etoposide derived from plasma concentration-time data after coadministration with VX-970 and in the absence of VX-970 [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Parts A, B: Objective tumor response (OR) as evaluated by computerized tomography (CT) scan and quantified by Response Criteria Evaluation (RECIST) 1.1 [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Part C2: Overall Response Rate in all subjects in Part C2 [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Parts C1, C2: Progression Free Survival (PFS) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Parts C1, C2: Response Duration (RD) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Parts C1, C2: Overall Survival (OS) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Parts C1, C2: Clinical benefit (Complete Response (CR) + Partial Reponse (PR) + Stable Disease (SD) of 6 months or greater) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Parts C1, C2: PK parameter estimates of VX-970 including maximum concentrations (Cmax), area under the curve (AUC), apparent volume at steady state (Vss), clearance (CL) and terminal elimination half-life (t1/2) [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 129
Study Start Date: December 2012
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part A
3 + 3 dose escalation of VX-970 in combination with gemcitabine as well as gemcitabine and cisplatin
Drug: VX-970 Drug: gemcitabine Drug: cisplatin
Experimental: Part B
3 + 3 dose escalation study of VX-970 in combination with cisplatin as well as cisplatin and etoposide
Drug: VX-970 Drug: cisplatin Drug: etoposide
Experimental: Part C1
VX-970 in combination with gemcitabine administered in subjects with advanced non-small cell lung cancer (NSCLC)
Drug: VX-970 Drug: gemcitabine
Experimental: Part C2
VX-970 in combination with cisplatin in subjects with advanced triple negative breast cancer (TNBC)
Drug: VX-970 Drug: cisplatin

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Disease status

  • Parts A and B: Histologically or cytologically confirmed advanced solid tumor that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective, or for whom regimens containing gemcitabine, cisplatin, and/or etoposide might be considered, and with measurable disease according to RECIST criteria
  • Part C1:

For Pre-screening:

  • Advanced (metastatic or locally-advanced unresectable and not eligible for definitive treatment, e.g., surgery/raidotherapy), histologically confirmed non-small cell lung cancer (NSCLC)
  • Available historical tumor specimen at the time of pre-screening or willing to provide a tumor biopsy (core) if the biopsy may be considered as part of standard clinical practice for the patient
  • Received or did not tolerate standard approved targeted therapy, if appropriate for tumor genotype
  • No evidence of disease progression on most recent clinical and radiologic assessment

For Screening:

  • TP53 mutation or ATM loss of expression documented on pre-screening of historical tumor specimen
  • Measurable disease according to RECIST criteria
  • Evidence of radiologic disease progression while on or after completing most recent line of therapy

    -Part C2:

  • Advanced (locally-advanced incurable or metastatic) histologically confirmed estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) negative breast cancer (TNBC).
  • Adequate available historical tumor specimen or willing to provide a tumor biopsy (core) if the biopsy may be considered as part of standard clinical practice for the patient
  • Measurable disease according to RECIST criteria

    • WHO performance status of 0 or 1
    • Life expectancy of ≥12 weeks
    • Hematological and biochemical indices within protocol specified ranges at screening.

Exclusion Criteria:

  • Radiotherapy (except for palliative reasons) endocrine therapy, immunotherapy, or chemotherapy during the previous 4 weeks (6 weeks for nitrosoureas and Mitomycin-C, and 4 weeks for investigational medicinal products) or less than 4 drug half-lives, whichever greater, before first dose of study drug.
  • Parts A and B:

    • Greater than 6 cycles of prior treatment with cisplatin and/or carboplatin.

      (a) History of prior dose reductions or dose interruptions while receiving cisplatin or carboplatin due to toxicity from the platinum or intolerance to either agent.

    • Subjects with a known history of Grade 4 thrombocytopenia or Grade 4 neutropenia while receiving prior therapy.
  • Part C1:

    • Any cytotoxic chemotherapy beyond 1 line of platinum-based chemotherapy in the advanced setting
    • Any prior gemcitabine for the treatment of NSCLC in any setting within 12 months
  • Part C2:

    • Any prior platinum therapy for breast cancer (including adjuvant or neoadjuvant) in any setting within 2 years of Screening
    • Relapse within 12 months of prior adjuvant or neoadjuvant chemotherapy
    • Any prior chemotherapy in the metastatic setting with the exception of either a taxane or an anthracycline in the first-line metastatic setting
  • 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 first dose of study drug. Any history of leptomeningeal metastases.
  • 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
  • Male subjects with partners of child-bearing potential must agree to adhere to contraception guidelines. 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
  • Serious cardiac or other co-morbid disease, as specified in the protocol
  • Prior bone marrow transplant or extensive radiotherapy to greater than 15% of bone marrow
  • Part C:

    • Current 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
  • Major surgery ≤2 weeks before starting study drug, or incomplete recovery from a prior major surgical procedure.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02157792

Contacts
Contact: Medical Monitor 617-341-6777 medicalinfo@vrtx.com

Locations
United States, Massachusetts
Recruiting
Boston, Massachusetts, United States
United States, New York
Recruiting
Lake Success, New York, United States
United States, Ohio
Recruiting
Columbus, Ohio, United States
United Kingdom
Recruiting
Manchester, England, United Kingdom
Recruiting
Newcastle, England, United Kingdom
Recruiting
Oxford, England, United Kingdom
Recruiting
Sutton, England, United Kingdom
Recruiting
Glasgow, Scotland, United Kingdom
Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated
  More Information

No publications provided

Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT02157792     History of Changes
Other Study ID Numbers: VX12-970-001  2012-003126-25 
Study First Received: June 1, 2014
Last Updated: October 15, 2015
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Vertex Pharmaceuticals Incorporated:
Solid Tumor
Advanced Solid Tumor

Additional relevant MeSH terms:
Cisplatin
Gemcitabine
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on February 08, 2016