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Trial record 3 of 3 for:    rigel | Recruiting Studies

Clinical Trial of Combined Fostamatinib and Paclitaxel in Ovarian Cancer

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ClinicalTrials.gov Identifier: NCT03246074
Recruitment Status : Recruiting
First Posted : August 11, 2017
Last Update Posted : March 7, 2019
Sponsor:
Collaborators:
Rigel Pharmaceuticals
Allegheny Health Network
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Ovarian Cancer Drug: Fostamatinib and Paclitaxel Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Clinical Trial of Combined Fostamatinib and Paclitaxel in Ovarian Cancer
Actual Study Start Date : April 3, 2018
Estimated Primary Completion Date : October 1, 2020
Estimated Study Completion Date : October 1, 2021


Arm Intervention/treatment
Experimental: Fostamatinib and Paclitaxel
Participants 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.
Drug: Fostamatinib and Paclitaxel

Drug: Fostamatinib (oral; 100 mg, 150 mg, or 200 mg)

Drug: Paclitaxel (60-80 mg/m2)

Other Name: Fostamatinib and Abraxane




Primary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events [ Time Frame: 3.5 years ]
    To determine the safety, tolerability, and maximum tolerated dose (MTD) of fostamatinib when administered in combination with weekly paclitaxel


Secondary Outcome Measures :
  1. Response rate of treatment with combination therapy [ Time Frame: 3.5 years ]
    To estimate the objective response rate in the study population treated with the combination of fostamatinib and paclitaxel

  2. Survival determination based on progression-free survival [ Time Frame: 10 years ]
    To estimate the progression-free survival in the study population treated with the combination of fostamatinib and paclitaxel

  3. Drug metabolism determination [ Time Frame: 3.5 years ]
    To assess the drug metabolism of fostamatinib when combined with weekly paclitaxel using Peak Plasma Concentration (Cmax in ng/mL)

  4. Drug metabolism determination [ Time Frame: 3.5 years ]
    To assess the drug metabolism of fostamatinib when combined with weekly paclitaxel using Area Under the Curve (AUC) (ng*hr/mL)

  5. Drug metabolism determination [ Time Frame: 3.5 years ]
    To assess the drug metabolism of fostamatinib when combined with weekly paclitaxel using half life (hours)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Must have ovarian, fallopian tube or peritoneal carcinoma.
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03246074


Contacts
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Contact: Hopkins Breast Trials 410-614-1361 hopkinsbreasttrials@jhmi.edu
Contact: Sidney Kimmel Cancer Center Clinical Research Office 410-955-8866 jhcccro@jhmi.edu

Locations
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United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21287
Contact: Hopkins Breast Trials       HopkinsBreastTrials@jhmi.edu   
Contact: Kimmel Cancer Center Clinical Research Office    410-955-8866    jhcccro@jhmi.edu   
Principal Investigator: Stephanie Gaillard, MD         
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Rigel Pharmaceuticals
Allegheny Health Network
Investigators
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Principal Investigator: Stephanie Gaillard, MD Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT03246074     History of Changes
Other Study ID Numbers: J1708
First Posted: August 11, 2017    Key Record Dates
Last Update Posted: March 7, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Individual participant data will not be shared.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
Phase I
Ovarian Cancer
Fostamatinib and Paclitaxel
Additional relevant MeSH terms:
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Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Paclitaxel
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action