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 June 2014 by Vertex Pharmaceuticals Incorporated
Sponsor:
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:
NCT02157792
First received: June 1, 2014
Last updated: June 16, 2014
Last verified: June 2014
  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:
  • 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 A, B, C1, C2, C3


Secondary Outcome Measures:
  • 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

  • Maximum tolerated dose (MTD) of VX-970 in combination with cisplatin and in combination with cisplatin and etoposide [ Time Frame: 1 Year ] [ Designated as safety issue: Yes ]
    Part B

  • PK parameter estimates of VX-970 derived from whole blood and/or plasma concentration-time data [ Time Frame: Lead-in Period to beginning of Cycle 2 (approximately 6 weeks) ] [ Designated as safety issue: No ]
    Parts A, B, C1, C2, C3

  • 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 week ] [ Designated as safety issue: No ]
    Part B

  • Objective tumor response (OR) as evaluated by CT scan and quantified by Response Criteria Evaluation (Response Evaluation Criteria in Solid Tumors - RECIST) [ Time Frame: Screening through radiologic follow-up (approximately 28 weeks) ] [ Designated as safety issue: No ]
    Parts A, B, C1, C2, C3

  • Progression-free survival (PFS) and Overall (OS) by time after initiation of treatment [ Time Frame: Approximately 28 weeks ] [ Designated as safety issue: No ]
    Parts C1, C2, C3


Estimated Enrollment: 105
Study Start Date: December 2012
Estimated Study Completion Date: April 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part A
3 + 3 dose escalation study of VX-970 when administered as a single agent and 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 when administered as a single agent, and in combination with cisplatin or cisplatin and etoposide
Drug: VX-970 Drug: cisplatin Drug: etoposide
Experimental: Part C1
Expanded cohort study of VX-970 in combination with cisplatin and gemcitabine in subjects with advanced squamous non-small cell lung cancer (NSCLC).
Drug: VX-970 Drug: gemcitabine Drug: cisplatin
Experimental: Part C2
Expanded cohort study of VX-970 in combination with cisplatin in subjects with advanced triple negative breast cancer (TNBC).
Drug: VX-970 Drug: cisplatin
Experimental: Part C3
Expanded cohort study of VX-970 in combination with cisplatin and etoposide in subjects with relapsed or refractory small cell lung cancer (SCLC).
Drug: VX-970 Drug: cisplatin Drug: etoposide

  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 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:

    • Advanced (Stage IIIB or IV, not eligible for resection or definitive radiotherapy), histologically confirmed squamous non-small cell lung cancer (NSCLC) and who have not previously received chemotherapy for metastatic disease.
    • Either has lesion amenable to biopsy before Day 1 or available archived tumor sample
    • Measurable disease according to RECIST criteria
  • 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.
    • Received a prior taxane-based regimen and no more than 1 additional regimen in the metastatic setting
    • Either has lesion amenable to biopsy before Day 1 or available archived tumor sample d. Measurable disease according to RECIST criteria
  • Part C3:

    • Histologically confirmed SCLC that has relapsed from, or was refractory to, prior chemotherapy. Refractory disease is defined as relapse within 90 days of completing chemotherapy, or lack of tumor response while on therapy.
    • Either has lesion amenable to biopsy before Day 1 or available archived tumor sample
    • Measurable disease according to RECIST criteria
  • 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
  • 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.

    • More than 2 prior distinct chemotherapy regimens used for treatment of advanced stage disease containing DNA damaging agents:
    • Subjects with a history of Grade 3 or 4 thrombocytopenia or Grade 4 neutropenia while receiving prior therapy with cisplatin, carboplatin, or any of the DNA damaging agents listed above.
  • Part C1:

    • prior platinum therapy for squamous NSCLC
    • Received prior treatment for metastatic NSCLC
  • Part C2:

    • More than 2 prior chemotherapy regimens for the treatment of metastatic breast cancer
    • Any prior platinum therapy for breast cancer in any setting
  • Part C3:

    • In relapsed SCLC, more than 2 prior chemotherapy regimens or, in refractory SCLC, more than 1 prior chemotherapy regimen
    • Has not received at least 1 cycle of platinum based chemotherapy for SCLC
  • Unresolved toxicity of Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or greater from previous anti-cancer therapy or radiotherapy
  • History of brain or 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
  • Major surgery ≤2 weeks before starting study drug, or incomplete recovery from a prior major surgical procedure
  • 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
  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
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: June 16, 2014
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
Etoposide
Etoposide phosphate
Gemcitabine
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on October 21, 2014