- Both Phase I and Phase II:
- Male and female subjects greater than or equal to 18 years of age.
dosing adverse event data are currently available on the use of topotecan in
combination with VX-970 (M6620) in subjects less than 18 years of age, children
are excluded from this study, but will be eligible for future pediatrics trials.
- - ECOG performance status less than or equal to 2
- Patients must have measurable disease, per RECIST 1.1.
Subjects with evaluable,
but not measurable disease will be eligible for Phase 1.
- - Subjects must not have received chemotherapy, or undergone major surgery within 4
weeks and radiotherapy within 24 hours prior to enrollment.
- - Adequate organ functions
- Hemoglobin greater than or equal to 9.0 g/dL
- Absolute neutrophil count greater than or equal to 1.5x10^9/L
- Platelets greater than or equal to 100x10^9/L
- Total Bilirubin less than or equal to 2.0 mg/dL
- Transaminases less than or equal to 2 x ULN or if liver metastases were
present, less than or equal to 3xULN
- Creatinine less than or equal to 1.5 mg/dL or creatinine clearance by
Cockcroft-Gault formula greater than or equal to 60 mL/min
- Ability of subject to understand and the willingness to sign a written informed
- - The effects of VX-970 (M6620) on the developing human fetus are unknown For this
reason and because topotecan is known to be teratogenic, women of child-bearing
potential and men must agree to use adequate contraception (hormonal or barrier
method of birth control; abstinence) prior to study entry, during study
participation and for 6 months after the last dose study therapy.
Should a woman
become pregnant or suspect she is pregnant while she or her partner is
participating in this study, she should inform her treating physician
- - Phase I:
- Subjects with histologically confirmed SCLC, NSCLC, ovarian cancer, cervical
cancer, and neuroendocrine cancers will be eligible.
Pathological confirmation of
diagnosis will be done at NCI Laboratory of Pathology. Patients with other
histologies will be allowed if no standard treatment options exist.
- - At least one prior chemotherapy
- NSCLC subjects with EGFR mutations or ALK translocations should have previously
received appropriate FDA approved therapies in addition to prior chemotherapy
- Phase II:
- Histological confirmation of SCLC, or extrapulmonary small cell cancer.
NCI confirmation of pathology is not required prior to starting treatment, every
effort will be made to obtain outside pathology to be reviewed by an NCI
- - Subjects with both platinum-sensitive and platinum-refractory disease will be
- Subjects with tumor amenable to potentially curative therapy.
- - Subjects who are receiving any other investigational agents.
- - History of allergic reactions attributed to compounds of similar chemical or biologic
composition to (study agent) or other agents used in study.
- - Subjects with symptomatic brain metastases will be excluded from trial secondary to
However, subjects who have had treatment for their brain metastasis
and whose brain disease is stable without steroid therapy for 1 week or on physiologic
doses of steroids may be enrolled.
- - Subjects requiring any medications or substances that are strong inhibitors or
inducers of CYP3A during the course of the study are ineligible.
strong inhibitors and inducers of CYP 3A4 are provided.
- - Subjects with evidence of severe or uncontrolled systemic disease, or any concurrent
condition, which could compromise participation in the study, including, but not
limited to, active or uncontrolled infection, immune deficiencies, Hepatitis B,
Hepatitis C, uncontrolled diabetes, uncontrolled hypertension, symptomatic congestive
heart failure, unstable angina pectoris, myocardial infarction within the past 6
months, uncontrolled cardiac arrhythmia, stroke/cerebrovascular accident within the
past 6 months, or psychiatric illness/social situations which would jeopardize
compliance with the protocol.
- - HIV-positive subjects on combination antiretroviral therapy are ineligible because of
the potential for pharmacokinetic interactions with VX-970 (M6620).
In addition, these
subjects are at increased risk of lethal infections when treated with
- - Pregnant women are excluded from this study because topotecan is a Class D agent with
the potential for teratogenic or abortifacient effects and because the effects of
VX-970 (M6620) on the developing human fetus are currently unknown.
because there is an unknown but potential risk for adverse events in nursing infants
secondary to treatment of the mother with topotecan or VX-970 (M6620), breastfeeding
should be discontinued if the mother is treated with these agents.