| Eligibility |
- Inclusion Criteria
1. Patients must have histologically or cytologically confirmed epithelial ovarian,
fallopian tube, or primary peritoneal carcinoma. Histologic documentation (via
the pathology report) of the original primary tumor is required.
2. Patients must have measurable disease, according to RECIST v1.1.
3. Patients must have recurrent, platinum-resistant disease (defined as having
relapsed within 6 months of last platinum-containing regimen) or be unable to
receive further platinum therapy. There is no limit on the number of prior
treatment regimens; however, patients may not have previously received weekly
paclitaxel in the recurrent setting. Previous dose dense paclitaxel as initial
therapy is allowable.
4. Patients must have the ability to take oral medications.
5. Females, age =18 years.
6. ECOG performance status =2 (Karnofsky =60%, see Appendix A).
7. Life expectancy of greater than 3 months.
8. Patients must have normal organ and marrow function.
9. Patients with a diagnosis of hypertension are required to have adequate blood
pressure control prior to enrollment, defined as blood pressure = 140/90 mmHg.
10. The effects of fostamatinib on the developing human fetus are unknown. For this
reason, women of childbearing potential must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry
and for the duration of study participation. Should a woman become pregnant or
suspect she is pregnant while she is participating in this study, she should
inform her treating physician immediately.
11. Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months are eligible for this trial
if the anti-retroviral therapy is not an excluded concurrent medication.
12. For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV
viral load must be undetectable on suppressive therapy, if indicated and the
suppressive therapy is not an excluded concurrent medication.
13. Patients with a history of hepatitis C virus (HCV) infection must have been
treated and cured. For patients with HCV infection who are currently on
treatment, they are eligible if they have an undetectable HCV viral load and the
HCV therapy is not an excluded concurrent medication.
14. Patients with treated brain metastases are eligible if follow-up brain imaging
after central nervous system (CNS)-directed therapy shows no evidence of
progression.
15. Patients who are willing and able to comply with the protocol and study
procedures.
Tumor biopsy or paracentesis for tumor cells before therapy (at baseline) and
after initiation of treatment (before Cycle 2) for at least 75% of subjects if
this is clinically and safely feasible to do so. For patients who have had tumor
tissue sampled within 6 months of enrollment and no intervening anti-neoplastic
therapy, archived tissue may satisfy the requirement of the pre-treatment biopsy
with permission of the protocol chair.
16. Patients with a prior or concurrent malignancy whose natural history or treatment
does not have the potential to interfere with the safety or efficacy assessment
of the investigational regimen are eligible for this trial, with permission of
the protocol chair.
17. Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of
cardiac function using the New York Heart Association Functional Classification.
To be eligible for this trial, patients should be class 2B or better.
18. The effects of fostamatinib on the developing human fetus are unknown. For this
reason and because spleen tyrosine kinase inhibitors as well as other therapeutic
agents used in this trial are known to be teratogenic, women of child-bearing
potential must agree to use adequate contraception (hormonal or barrier method of
birth control; abstinence) prior to study entry and for the duration of study
participation. 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 immediately.
19. Ability to understand and the willingness to sign a written informed consent
document.
- Exclusion Criteria
1. Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study. Hormonal therapy
directed at the malignant tumor must be discontinued at least one week prior to
registration.
2. Patients who have not recovered (CTCAE v4.03 grade =1) from adverse events due to
agents administered more than 4 weeks earlier, unless those events are deemed to
have returned to baseline, are irreversible, or are unlikely to develop into a
life-threatening condition at the permission of the Protocol Chair (e.g.,
alopecia).
3. Patients who are currently receiving or have previously received any other
investigational agents within 3 weeks prior to entering the study.
4. Patients with known untreated brain metastases, as progressive neurologic
dysfunction may develop that would confound the evaluation of neurologic and
other adverse events.
5. Patients with Grade 2 or greater neuropathy.
6. History of allergic reactions attributed to compounds of similar chemical or
biologic composition to fostamatinib or paclitaxel. Patients who are able to
tolerate paclitaxel on a desensitization protocol will be allowed.
7. Strong CYP3A4 inhibitors or inducers should not be used within 3 days of Day 1
dosing until the end of study. Moderate CYP3A4 inhibitors or inducers should be
used with caution.
8. Uncontrolled intercurrent illness
9. Pregnant women are excluded from this study because the potential for teratogenic
or abortifacient effects of fostamatinib are unknown. Because there is an unknown
but potential risk for adverse events in nursing infants secondary to treatment
of the mother with fostamatinib, breastfeeding should be discontinued if the
mother is treated with fostamatinib. These potential risks may also apply to
other agents used in this study.
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