Clinical Trial of Combined Fostamatinib and Paclitaxel in Ovarian Cancer

NCT03246074 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: J1708IRB00271541
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 3

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 ovarian cancer when given together.

Conditions

Ovarian Cancer

Keywords

Phase I; Ovarian Cancer; Fostamatinib and Paclitaxel

Outcome Measures

Primary Outcomes (2)

• Safety and Tolerability of Fostamatinib

  The number of dose limiting toxicities (DLTs) at each dose level will be reported. All toxicities will be reported by type and grade using NCI CTCAE version 4.03.

  First cycle (28 days) of treatment

• Maximum Tolerated Dose (MTD) of Fostamatinib

  The MTD will be determined as the dose level with the highest probability of having a risk of DLT in the acceptable region based on the mTPI dose-escalation design. Measured at 28 days (DLT period).

  28 days

Secondary Outcomes (5)

• Objective Response Rate in the Study Population Treated With the Combination of Fostamatinib and Paclitaxel

  5 years

• Progression-free Survival in the Study Population Treated With the Combination of Fostamatinib and Paclitaxel

  5 years

• Pharmacokinetic (PK) Profile of Fostamatinib When Combined With Weekly Paclitaxel - Tmax

  First cycle (28 days) of treatment

• Pharmacokinetic (PK) Profile of Fostamatinib When Combined With Weekly Paclitaxel - Cmax

  First cycle (28 days) of treatment

• Pharmacokinetic (PK) Profile of Fostamatinib When Combined With Weekly Paclitaxel - Area Under the Curve (AUC) 0-6hours

  First cycle (28 days) of treatment

Study Arms (3)

Fostamatinib 100 mg bid and Paclitaxel

EXPERIMENTAL

Participants will receive paclitaxel on Days 1, 8 and 15 of each cycle and fostamatinib at a fixed oral dose of 100mg twice daily throughout each 28-day cycle.

Drug: Fostamatinib 100 mg bid and Paclitaxel

Fostamatinib 150 mg bid and Paclitaxel

EXPERIMENTAL

Participants will receive paclitaxel on Days 1, 8 and 15 of each cycle and fostamatinib at a fixed oral dose of 150mg twice daily throughout each 28-day cycle.

Drug: Fostamatinib 150 mg bid and Paclitaxel

Fostamatinib 200 mg bid and Paclitaxel

EXPERIMENTAL

Participants will receive paclitaxel on Days 1, 8 and 15 of each cycle and fostamatinib at a fixed oral dose of 150mg twice daily throughout each 28-day cycle.

Drug: Fostamatinib 200 mg bid and Paclitaxel

Interventions

Fostamatinib 100 mg bid and Paclitaxel DRUG

Drug: Fostamatinib (oral; 100 mg bid) Drug: Paclitaxel (60-80 mg/m2)

Also known as: Fostamatinib and Abraxane

Fostamatinib 100 mg bid and Paclitaxel

Fostamatinib 150 mg bid and Paclitaxel DRUG

Drug: Fostamatinib (oral; 150 mg bid) Drug: Paclitaxel (60-80 mg/m2)

Also known as: Fostamatinib and Abraxane

Fostamatinib 150 mg bid and Paclitaxel

Fostamatinib 200 mg bid and Paclitaxel DRUG

Drug: Fostamatinib (oral; 200 mg bid) Drug: Paclitaxel (60-80 mg/m2)

Also known as: Fostamatinib and Abraxane

Fostamatinib 200 mg bid and Paclitaxel

Eligibility Criteria

• Age: 18 Years - 100 Years
• Gender Eligibility Details: Must have ovarian, fallopian tube or peritoneal carcinoma.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Patients must have measurable disease, according to RECIST v1.1.
• 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.
• Patients must have the ability to take oral medications.
• Females, age ≥18 years.
• ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A).
• Life expectancy of greater than 3 months.
• Patients must have normal organ and marrow function.
• Patients with a diagnosis of hypertension are required to have adequate blood pressure control prior to enrollment, defined as blood pressure ≤ 140/90 mmHg.
• 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.
• 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.
• 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.
• 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.
• Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression.
• Patients who are willing and able to comply with the protocol and study procedures.

You may not qualify if:

• 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.
• 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).
• Patients who are currently receiving or have previously received any other investigational agents within 3 weeks prior to entering the study.
• Patients with known untreated brain metastases, as progressive neurologic dysfunction may develop that would confound the evaluation of neurologic and other adverse events.
• Patients with Grade 2 or greater neuropathy.
• 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.
• 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.
• Uncontrolled intercurrent illness
• 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.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Rigel Pharmaceuticals: collaborator
• Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute): collaborator

Study Sites (3)

Sibley Memorial Hospital

Washington D.C., District of Columbia, 20016, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

University of Pennsylvania Health System

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

fostamatinib; BID protein, human; Paclitaxel; Albumin-Bound Paclitaxel

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Stephanie Gaillard, MD PhD
• Organization: SKCCC at Johns Hopkins

stephanie.gaillard@jhmi.edu

410-955-3774

Study Officials

• Stephanie Gaillard, MD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2017
• First Posted: August 11, 2017
• Study Start: April 3, 2018
• Primary Completion: August 9, 2022
• Study Completion: April 3, 2023
• Last Updated: October 24, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)