Clinical Trials /

Clinical Trial of Combined Fostamatinib and Paclitaxel in Ovarian Cancer

NCT03246074

Description:

This research is being done to test the safety of the combination of the study drugs fostamatinib and paclitaxel. This study tests different doses of the drugs to see which doses are safest in people with ovaria cancer when given together.

Related Conditions:
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Clinical Trial of Combined Fostamatinib and Paclitaxel in Ovarian Cancer
  • Official Title: Phase I Clinical Trial of Combined Fostamatinib and Paclitaxel in Ovarian Cancer

Clinical Trial IDs

  • ORG STUDY ID: J1708
  • NCT ID: NCT03246074

Conditions

  • Ovarian Cancer

Interventions

DrugSynonymsArms
Fostamatinib and PaclitaxelFostamatinib and AbraxaneFostamatinib and Paclitaxel

Purpose

This research is being done to test the safety of the combination of the study drugs fostamatinib and paclitaxel. This study tests different doses of the drugs to see which doses are safest in people with ovaria cancer when given together.

Detailed Description

      This is a phase I, open-label, non-randomized multicenter dose-escalation study with the
      primary objective to determine the maximally tolerated dose (MTD) of fostamatinib when
      administered with weekly paclitaxel in women with recurrent platinum-resistant ovarian,
      fallopian tube, or primary peritoneal cancer.

      Between 8 and 18 adult female subjects will be enrolled and receive weekly paclitaxel in
      combination with increasing doses of fostamatinib. There will be three dosing intervals of
      fostamatinib (100 mg bid, 150 mg bid, and 200mg bid) selected based on prior phase I studies
      of single agent fostamatinib. Dose-escalation will follow a modified toxicity probability
      interval (mTPI) design. In this study, up to 18 adult female subjects will be enrolled and
      receive weekly paclitaxel in combination with fostamatinib at the MTD of the combination; at
      least 6 patients with receive fostamatinib plus paclitaxel at the MTD.
    

Trial Arms

NameTypeDescriptionInterventions
Fostamatinib and PaclitaxelExperimentalParticipants will receive paclitaxel on Days 1, 8 and 15 of each cycle and fostamatinib at a fixed oral dose twice daily throughout each 28-day cycle. The dose of fostamatinib will be determined by the enrollment dose level. Given the mTPI design, dose-escalation decisions will be made based on the three dosing intervals, where the underdosing interval corresponds to dose escalation (E), overdosing interval corresponds to dose de-escalation (D), and proper dosing corresponds to staying at the current dose (S). The initial dose level will be Level 1 of Table 1. Participants will be individually continually assessed for DLT. The associated dose-escalation decisions are presented in Table 2. For illustration, suppose a cohort of 3 patients is at the current dose.
  • Fostamatinib and Paclitaxel

Eligibility Criteria

        -  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. 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.

              10. Patients who are willing and able to comply with the protocol and study
                  procedures including willingness to undergo tumor biopsy or paracentesis for
                  tumor cells before therapy (at baseline) and after initiation of treatment
                  (before Cycle 2) for all subjects if this is clinically and safely feasible to do
                  so.

          -  Exclusion Criteria

               1. Patients who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for
                  nitrosoureas or mitomycin C) prior to entering the study or those who have not
                  recovered from adverse events due to agents administered more than 3 weeks
                  earlier. Hormonal therapy directed at the malignant tumor must be discontinued at
                  least one week prior to registration.

               2. Patients who are currently receiving or have previously received any other
                  investigational agents within 3 weeks prior to entering the study.

               3. Patients with known brain metastases, as progressive neurologic dysfunction may
                  develop that would confound the evaluation of neurologic and other adverse
                  events.

               4. Patients with Grade 2 or greater neuropathy.

               5. 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.

               6. 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.

               7. Uncontrolled intercurrent illness

               8. 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.

               9. Subject with known history of human immunodeficiency virus (HIV) or if known
                  seropositive for hepatitis C virus (HCV) or hepatitis B virus (HBV). HIV-positive
                  patients on combination antiretroviral therapy are ineligible because of the
                  potential immunosuppressive effects of and the potential for pharmacokinetic
                  interactions with fostamatinib. In addition, these patients are at increased risk
                  of lethal infections when treated with marrow-suppressive therapy.

                  NOTE: Patients seropositive for hepatitis B or C may be included if confirmed
                  hepatitis C RIBA negative or HCV RNA negative (qualitative).

              10. Patients with prior malignancy, except for adequately treated basal cell or
                  squamous cell skin cancer, in situ cervical cancer, or other cancer from which
                  the subject has been disease free for at least three years.
      
Maximum Eligible Age:100 Years
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Treatment-Emergent Adverse Events
Time Frame:3.5 years
Safety Issue:
Description:To determine the safety, tolerability, and maximum tolerated dose (MTD) of fostamatinib when administered in combination with weekly paclitaxel

Secondary Outcome Measures

Measure:Response rate of treatment with combination therapy
Time Frame:3.5 years
Safety Issue:
Description:To estimate the objective response rate in the study population treated with the combination of fostamatinib and paclitaxel
Measure:Survival determination based on progression-free survival
Time Frame:10 years
Safety Issue:
Description:To estimate the progression-free survival in the study population treated with the combination of fostamatinib and paclitaxel
Measure:Drug metabolism determination
Time Frame:3.5 years
Safety Issue:
Description:To assess the drug metabolism of fostamatinib when combined with weekly paclitaxel using Peak Plasma Concentration (Cmax in ng/mL)
Measure:Drug metabolism determination
Time Frame:3.5 years
Safety Issue:
Description:To assess the drug metabolism of fostamatinib when combined with weekly paclitaxel using Area Under the Curve (AUC) (ng*hr/mL)
Measure:Drug metabolism determination
Time Frame:3.5 years
Safety Issue:
Description:To assess the drug metabolism of fostamatinib when combined with weekly paclitaxel using half life (hours)

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Trial Keywords

  • Phase I
  • Ovarian Cancer
  • Fostamatinib and Paclitaxel

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