Clinical Trials

The James Cancer Center Columbus, OH

open for enrollment

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

Protocol: OSU-13211

Full 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

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

Are you eligible?

Inclusion 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/radiotherapy), 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

For Screening:

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.

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

-Part C3:

Advanced (locally-advanced incurable or metastatic) histologically confirmed SCLC

that is platinum-resistant, defined as disease progression during initial treatment

with a platinum-based regimen or progression within 90 days of completion of platinum

therapy. Subjects with platinum-resistant disease may receive a second-line

non-platinum-based chemotherapy and subsequently be enrolled to this study. Subjects

who received and are resistant to a second-line platinum-based chemotherapy may also

be enrolled into the study.

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 week

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. One

additional line of non-platinum based therapy in the advanced setting

1. Pre-screening Only*: Subjects may currently be receiving platinum-based

chemotherapy in the advanced setting, or have completed 1 line of

platinum-based chemotherapy and are currently receiving a second-line

non-platinum-based therapy or maintenance therapy

2. There is no restriction on prior immunotherapy or targeted therapy unless

combined together with a cytotoxic agent

Any prior gemcitabine for the treatment of NSCLC in any setting within 6 months

Subjects who are known to be TP53 wild-type, unless they are determined to have

ATM loss of expression during screening or pre-screening or until all the

planned subjects with TP53 mutation are enrolled as determined by the medical

monitor

Subjects with unknown TP53 mutational status will be enrolled until the group of

approximately 10 subjects

Exclusion 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/radiotherapy), 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

For Screening:

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.

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

-Part C3:

Advanced (locally-advanced incurable or metastatic) histologically confirmed SCLC

that is platinum-resistant, defined as disease progression during initial treatment

with a platinum-based regimen or progression within 90 days of completion of platinum

therapy. Subjects with platinum-resistant disease may receive a second-line

non-platinum-based chemotherapy and subsequently be enrolled to this study. Subjects

who received and are resistant to a second-line platinum-based chemotherapy may also

be enrolled into the study.

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 week

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. One

additional line of non-platinum based therapy in the advanced setting

1. Pre-screening Only*: Subjects may currently be receiving platinum-based

chemotherapy in the advanced setting, or have completed 1 line of

platinum-based chemotherapy and are currently receiving a second-line

non-platinum-based therapy or maintenance therapy

2. There is no restriction on prior immunotherapy or targeted therapy unless

combined together with a cytotoxic agent

Any prior gemcitabine for the treatment of NSCLC in any setting within 6 months

Subjects who are known to be TP53 wild-type, unless they are determined to have

ATM loss of expression during screening or pre-screening or until all the

planned subjects with TP53 mutation are enrolled as determined by the medical

monitor

Subjects with unknown TP53 mutational status will be enrolled until the group of

approximately 10 subjects