Ovarian CancerPhase 1NCT03246074
Clinical Trial of Combined Fostamatinib and Paclitaxel in Ovarian Cancer
A Phase 1 study testing Fostamatinib 100 mg bid and Paclitaxel, Fostamatinib 150 mg bid and Paclitaxel and Fostamatinib 200 mg bid and Paclitaxel in people with Ovarian Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 100 years, women only
- Conditions the study is for
- Ovarian Cancer
- What is being tested?
- Fostamatinib 100 mg bid and Paclitaxel, Fostamatinib 150 mg bid and Paclitaxel and Fostamatinib 200 mg bid and Paclitaxel
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 3 sitesUnited States
- Study dates
- 3 Apr 2018to 3 Apr 2023
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- 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.
- 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.
- 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.
- 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.
- 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.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, 21287
University of Pennsylvania Health System
Philadelphia, Pennsylvania, 19104
Sibley Memorial Hospital
Washington D.C., District of Columbia, 20016
About this study
Official title: Phase I Clinical Trial of Combined Fostamatinib and Paclitaxel in Ovarian Cancer
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.
Read the 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 regimens of fostamatinib (100 mg bid, 150 mg bid, and 200mg bid) selected based on the FDA approved doses and 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 will receive fostamatinib plus paclitaxel at the MTD. A total of up to 30 patients will be enrolled in this study.
- Conditions
- Ovarian Cancer
- Being tested
- Fostamatinib 100 mg bid and Paclitaxel, Fostamatinib 150 mg bid and Paclitaxel, Fostamatinib 200 mg bid and Paclitaxel
- Keywords
- Phase I, Ovarian Cancer, Fostamatinib and Paclitaxel
- Medical subject headings
- Ovarian Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fostamatinib 100 mg bid and PaclitaxelDrug
Also called Fostamatinib and Abraxane
Drug: Fostamatinib (oral; 100 mg bid)
Drug: Paclitaxel (60-80 mg/m2)
Fostamatinib 150 mg bid and PaclitaxelDrug
Also called Fostamatinib and Abraxane
Drug: Fostamatinib (oral; 150 mg bid)
Drug: Paclitaxel (60-80 mg/m2)
Fostamatinib 200 mg bid and PaclitaxelDrug
Also called Fostamatinib and Abraxane
Drug: Fostamatinib (oral; 200 mg bid)
Drug: Paclitaxel (60-80 mg/m2)
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: Fostamatinib 200 mg bid and Paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
Measured: 28 days
Secondary outcomes (5)
Objective Response Rate in the Study Population Treated With the Combination of Fostamatinib and Paclitaxel
Number of participants within each objective response as seen on imaging/RECIST 1.1. Per response evaluation criteria in solid tumors criteria (RECIST v1.1) for target lesions: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Measured: 5 years
Progression-free Survival in the Study Population Treated With the Combination of Fostamatinib and Paclitaxel
Progression-free survival (PFS) will be described by the method of Kaplan and Meier. Median PFS in months will be estimated along with its 95% confidence interval. Per response evaluation criteria in solid tumors (RECIST v1.1), Progressive Disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Measured: 5 years
Pharmacokinetic (PK) Profile of Fostamatinib When Combined With Weekly Paclitaxel - Tmax
Tmax (hours) was used to summarize pharmacokinetic marker profile for fostamatinib. Tmax (hours): Time to reach maximum plasma concentration of R406, the active meta
Measured: First cycle (28 days) of treatment
Pharmacokinetic (PK) Profile of Fostamatinib When Combined With Weekly Paclitaxel - Cmax
Cmax (ng/mL) was used to summarize pharmacokinetic marker profile for fostamatinib. Cmax (ng/mL): Maximum plasma concentration of R406.
Measured: First cycle (28 days) of treatment
Pharmacokinetic (PK) Profile of Fostamatinib When Combined With Weekly Paclitaxel - Area Under the Curve (AUC) 0-6hours
AUC0-6h (ng*h/mL) was used to summarize pharmacokinetic marker profile for fostamatinib. AUC0-6h (ng*h/mL): Area under the concentration-time curve for R406 up to 6 hours post-dosing.
Measured: First cycle (28 days) of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Aug 2017
- Study start3 Apr 2018
- Primary completion9 Aug 2022
- Study completion3 Apr 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Ovarian CancerStudies of the same condition, open and under way.
- More trials run by Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Rigel Pharmaceuticals, Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)
- Responsible party
- Sponsor
- Investigators
- Stephanie Gaillard, MD, Principal investigator, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03246074
- Sponsor's protocol ID
- J1708
- Other IDs
- IRB00271541
- Status last verified
- Oct 2024
- First submitted
- 15 Jun 2017
- Last updated
- 24 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data will not be shared.
Study at a glance
From the registry record, last updated by the sponsor on 24 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Clinical Trial of Combined Fostamatinib and Paclitaxel in Ovarian Cancer
- ClinicalTrials.gov ID
- NCT03246074
- Acronym / sponsor ID
- J1708
- Conditions
- Ovarian Cancer
- Keywords
- Phase I, Ovarian Cancer, Fostamatinib and Paclitaxel
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Collaborators
- Rigel Pharmaceuticals, Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)
- Study start
- 3 Apr 2018 (actual)
- Primary completion
- 9 Aug 2022 (actual)
- Study completion
- 3 Apr 2023 (actual)
- First posted
- 11 Aug 2017 (actual)
- Results
- Posted 19 Sep 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 regimens of fostamatinib (100 mg bid, 150 mg bid, and 200mg bid) selected based on the FDA approved doses and 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 will receive fostamatinib plus paclitaxel at the MTD. A total of up to 30 patients will be enrolled in this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Fostamatinib 100 mg bid and Paclitaxel | Experimental | Drug: Fostamatinib 100 mg bid and PaclitaxelParticipants 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. |
| Fostamatinib 150 mg bid and Paclitaxel | Experimental | Drug: Fostamatinib 150 mg bid and PaclitaxelParticipants 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. |
| Fostamatinib 200 mg bid and Paclitaxel | Experimental | Drug: Fostamatinib 200 mg bid and PaclitaxelParticipants 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. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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.
Key exclusion criteria (9 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fostamatinib 100 mg bid and PaclitaxelAlso: Fostamatinib and AbraxaneDrug: Fostamatinib (oral; 100 mg bid) Drug: Paclitaxel (60-80 mg/m2) | Drug | Fostamatinib 100 mg bid and Paclitaxel |
| Fostamatinib 150 mg bid and PaclitaxelAlso: Fostamatinib and AbraxaneDrug: Fostamatinib (oral; 150 mg bid) Drug: Paclitaxel (60-80 mg/m2) | Drug | Fostamatinib 150 mg bid and Paclitaxel |
| Fostamatinib 200 mg bid and PaclitaxelAlso: Fostamatinib and AbraxaneDrug: Fostamatinib (oral; 200 mg bid) Drug: Paclitaxel (60-80 mg/m2) | Drug | Fostamatinib 200 mg bid and Paclitaxel |
Primary outcome
Safety and Tolerability of Fostamatinib
Time frame: First cycle (28 days) of treatment
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.
Maximum Tolerated Dose (MTD) of Fostamatinib
Time frame: 28 days
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).
5 secondary outcomes
Objective Response Rate in the Study Population Treated With the Combination of Fostamatinib and Paclitaxel
Time frame: 5 years
Progression-free Survival in the Study Population Treated With the Combination of Fostamatinib and Paclitaxel
Time frame: 5 years
Pharmacokinetic (PK) Profile of Fostamatinib When Combined With Weekly Paclitaxel - Tmax
Time frame: First cycle (28 days) of treatment
Pharmacokinetic (PK) Profile of Fostamatinib When Combined With Weekly Paclitaxel - Cmax
Time frame: First cycle (28 days) of treatment
Pharmacokinetic (PK) Profile of Fostamatinib When Combined With Weekly Paclitaxel - Area Under the Curve (AUC) 0-6hours
Time frame: First cycle (28 days) of treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. Individual participant data will not be shared.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stephanie Gaillard, MD principal investigator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Fostamatinib 100 mg bid and Paclitaxel, Fostamatinib 150 mg bid and Paclitaxel and Fostamatinib 200 mg bid and Paclitaxel in people with Ovarian Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and Tolerability of Fostamatinib (time frame: First cycle (28 days) of treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Oct 2024.