Ovarian CancerPhase 2NCT02440425
Dose Dense Paclitaxel With Pembrolizumab (MK-3475) in Platinum Resistant Ovarian Cancer
A Phase 2 study testing Pembrolizumab and Paclitaxel in people with Ovarian Cancer, run by H. Lee Moffitt Cancer Center and Research Institute at 3 sites in United States.
Trial summary
The purpose of this study is to find out if the combination of Paclitaxel once per week with Pembrolizumab once every 3 weeks will help participants with this disease. Researchers want to find out the effectiveness of the drug combination to improve the delay of cancer progression or death and compare it to historical… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ovarian Cancer
- What is being tested?
- Pembrolizumab and Paclitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 3 sitesUnited States
- Study dates
- 20 Oct 2015to 27 May 2021
- Phase
- Phase 2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Must have confirmation of the histologic diagnosis of high-grade (grade 2-3) epithelial, non-mucinous, non-borderline, ovarian, fallopian tube, or primary peritoneal carcinoma. May be based on original pathology report or review of original slides.
- Willing and able to provide written informed consent/assent and authorization
- ≥ 18 years of age on day of signing informed consent
- Disease must have been persistent or have recurred within 6 months of prior platinum therapy. Disease may not have progressed during prior platinum therapy (i.e., refractory).
- Have measurable disease or detectable (non-measureable) disease
- Measurable disease: must have at least one "target lesion" to be used to assess response on this protocol.
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- Prior Therapy:
- Have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound. This initial treatment may have included intraperitoneal therapy, consolidation, non-cytotoxic agents (biologic/ targeted) or extended therapy administered after surgical or non-surgical assessment. If patients were treated initially with paclitaxel for their primary disease, this can have been given weekly or every 3 weeks. The most recent therapy and any therapies subsequent to initial therapy, however, cannot have contained weekly paclitaxel. If the immediate prior (most recent therapy) is the initial therapy, it may not have been with weekly paclitaxel.
- Allowed to receive (not required to receive), 2 additional cytotoxic regimens for management of recurrent or persistent disease, with no more than 1 non-platinum regimen. Treatment with weekly paclitaxel for recurrent or persistent disease is NOT allowed.
- Allowed to receive(not required to receive), non-cytotoxic (biologic/targeted) therapy as part of their primary treatment regimen. Allowed to receive (not required to receive), non-cytotoxic (biologic/targeted) therapy as part of their treatment for recurrent or persistent disease and/or as treatment for recurrent or persistent disease. If non-cytotoxic (biologic/targeted) therapy is given alone (i.e., not in combination with cytotoxic chemotherapy) it will NOT count as a prior regimen.
- Have tissue from an archival tissue sample that has been identified and confirmed as available for study, or newly obtained core or excisional biopsy of a tumor lesion
- Have received 1 prior regimen must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2. If have received 2 or 3 prior regimens, must have an ECOG Performance Status of 0 or 1.
- Adequate organ function as defined in the protocol
- Recovery from effects of recent surgery, radiotherapy, or chemotherapy: Should be free of active infection requiring antibiotics (with exception of uncomplicated UTI); Any hormonal therapy directed at the malignant tumor must be discontinued at least 2 weeks prior to registration (continuation of hormone replacement therapy is permitted); Any other prior therapy directed at the malignant tumor, including chemotherapy, biologic/targeted and immunologic agents, must be discontinued at least 2 weeks prior to registration and at least 3 weeks before day 1 on trial.
- Women of Childbearing Potential (WOCBP): Negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- WOCBP willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication.
Who cannot join
- Have low-grade or non-epithelial cancers, mucinous cancers, and/or borderline low-malignant potential cancers
- Currently participating in/have participated in a study of an investigational agent or is or has been using an investigational device within 4 weeks of the first dose of treatment
- Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
- Had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to prior therapies
- Had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 3 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. - Note: If received major surgery, must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
- History of other invasive malignancies (with exception of non-melanoma skin cancer and or in situ cancers that have undergone potentially curative therapy) are excluded if there is any evidence of other malignancy being present within the last 3 years. Patients are also excluded if their previous cancer treatment contraindicates this protocol therapy.
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- Have received prior radiotherapy to any portion of the abdominal cavity or pelvis OTHER THAN for the treatment of ovarian, fallopian tube, or primary peritoneal cancer within the last 3 years are excluded. Prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than 3 years prior to registration, and the patient remains free of recurrent or metastatic disease.
- Have received prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment of ovarian, fallopian tube, or primary peritoneal cancer within the last 3 year. May have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than 3 years prior to registration, and the patient remains free of recurrent or metastatic disease.
- History of synchronous endometrial cancer unless all of the following conditions are met: Stage not greater than I-A (FIGO 2010 staging criteria); no more than superficial myometrial invasion (<50%), without vascular or lymphatic invasion; no poorly differentiated subtypes, including papillary serous, clear cell or other FIGO Grade 3 lesions and it has been greater than 3 years since diagnosis and there have been no recurrences.
- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment.
- Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment..
- Evidence of interstitial lung disease, any active, non-infectious pneumonitis, or known active tuberculosis
- An active infection requiring systemic therapy
- History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with participation for the full duration of the trial, or is not in the best interest of the participant, in the opinion of the treating physician or the principal or study investigator.
- Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
- Pregnant or breastfeeding, or expecting to conceive children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
- Received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody
- Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
- Known active Hepatitis B or Hepatitis C
- Received a live vaccine within 30 days prior to the first dose of trial treatment
- Peripheral neuropathy Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or higher
- Known hypersensitivity to pembrolizumab or any of its excipients
- Known hypersensitivity to paclitaxel
- Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Duke University
Durham, North Carolina, 27710
VCU Massey Cancer Center
Richmond, Virginia, 23298
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612
About this study
Official title: Phase 2 Trial of Dose Dense (Weekly) Paclitaxel With Pembrolizumab (MK-3475) in Platinum Resistant Recurrent Ovarian Cancer
The purpose of this study is to find out if the combination of Paclitaxel once per week with Pembrolizumab once every 3 weeks will help participants with this disease. Researchers want to find out the effectiveness of the drug combination to improve the delay of cancer progression or death and compare it to historical data for weekly paclitaxel alone, and assess safety.
- Conditions
- Ovarian Cancer
- Being tested
- Pembrolizumab, Paclitaxel
- Keywords
- platinum resistant, recurrent, persistent, epithelial, ovarian, fallopian tube, primary peritoneal, carcinoma
- Medical subject headings
- Ovarian Neoplasms, Recurrence, Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Also called MK-3475, KEYTRUDA®
Pembrolizumab: 200 mg, every (Q) 3 weeks, via intravenous (IV) infusion, until progression or toxicity (or up to 24 months). The first cycle will begin on day 8.
PaclitaxelDrug
Also called Taxol, Onxal
Paclitaxel: 80 mg/m^2, Q week for 3 weeks, via IV infusion, until progression or toxicity (or complete response if at least 6 cycles, at the discretion of the investigator and participant). Cycle 1 will have an extra lead in week (4 weeks total) with Paclitaxel only on week 1.
| Study group | Role | What they receive |
|---|---|---|
| Combination Therapy | Experimental | Combination Therapy: Pembrolizumab (experimental use) and Paclitaxel (standard use). All trial treatments will be administered on an outpatient basis. One cycle equals 21 days. The first cycle is 28 days with Pembrolizumab given on day 8 in order to determine paclitaxel tolerance. Receives: Drug: Pembrolizumab; Drug: Paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival (PFS) at 6 Months
6-month progression-free survival of the combination of weekly paclitaxel with pembrolizumab (MK-3475) for those patients who received treatment and were evaluable (had one response assessment scan by RECIST 1.1) . 6-month PFS: The proportion of patients at 6 months alive without progressive disease. Progressive Disease (PD): Sum of the longest diameters (SLD) increased by at least 20% from the smallest value on study (including baseline, if that is the smallest).
Measured: 6 months
Occurrence of Adverse Events
Safety of the combination of paclitaxel weekly with pembrolizumab every 3 weeks (Q3W). Serious Adverse Events and Adverse Events will be reported in that Results Data section, according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) V4.0.
Measured: 2 years, 6 months
Secondary outcomes (4)
Response Rate (RR)
Proportion of participants who respond to the regimen by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. RECIST v1.1: Complete Response (CR) - Disappearance of all extranodal target lesions. All pathological lymph nodes must have decreased to <10 mm in short axis. Partial Response (PR) - At least a 30% decrease in the SLD of target lesions, taking as reference the baseline sum diameters. RR=CR + PR.
Measured: Up to 36 months
Disease Control Rate (DCR)
DCR: The percentage of participants complete response, partial response and stable disease to a therapeutic intervention in clinical trials of anticancer agents. Stable Disease (SD) - Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. DCR=CR + PR + (SD x 2 mo.)
Measured: Up to 36 months
Duration of Response (DOR)
Duration of Response in months. DOR= Duration from first observation of partial response to the time of disease progression.
Measured: Up to 36 months
Median Overall Survival (OS)
OS: The time from randomization until death from any cause.
Measured: Up to 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2015 (estimated)
- Study start20 Oct 2015
- Primary completionApr 2020
- Study completion27 May 2021
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 H. Lee Moffitt Cancer Center and Research InstituteThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Robert Wenham, M.D., Principal investigator, H. Lee Moffitt Cancer Center and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02440425
- Sponsor's protocol ID
- MCC-18207
- Status last verified
- Sep 2022
- First submitted
- 7 May 2015
- Last updated
- 7 Oct 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Trial of Dose Dense (Weekly) Paclitaxel With Pembrolizumab (MK-3475) in Platinum Resistant Recurrent Ovarian Cancer
- ClinicalTrials.gov ID
- NCT02440425
- Acronym / sponsor ID
- MCC-18207
- Conditions
- Ovarian Cancer
- Keywords
- platinum resistant, recurrent, persistent, epithelial, ovarian, fallopian tube, primary peritoneal, carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 20 Oct 2015 (actual)
- Primary completion
- Apr 2020 (actual)
- Study completion
- 27 May 2021 (actual)
- First posted
- 12 May 2015 (estimated)
- Results
- Posted 3 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to find out if the combination of Paclitaxel once per week with Pembrolizumab once every 3 weeks will help participants with this disease. Researchers want to find out the effectiveness of the drug combination to improve the delay of cancer progression or death and compare it to historical data for weekly paclitaxel alone, and assess safety.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Combination Therapy | Experimental | Drug: Pembrolizumab, Drug: PaclitaxelCombination Therapy: Pembrolizumab (experimental use) and Paclitaxel (standard use). All trial treatments will be administered on an outpatient basis. One cycle equals 21 days. The first cycle is 28 days with Pembrolizumab given on day 8 in order to determine paclitaxel tolerance. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Must have confirmation of the histologic diagnosis of high-grade (grade 2-3) epithelial, non-mucinous, non-borderline, ovarian, fallopian tube, or primary peritoneal carcinoma. May be based on original pathology report or review of original slides.
- Willing and able to provide written informed consent/assent and authorization
- ≥ 18 years of age on day of signing informed consent
- Disease must have been persistent or have recurred within 6 months of prior platinum therapy. Disease may not have progressed during prior platinum therapy (i.e., refractory).
- Have measurable disease or detectable (non-measureable) disease
Key exclusion criteria (24 listed)
- Have low-grade or non-epithelial cancers, mucinous cancers, and/or borderline low-malignant potential cancers
- Currently participating in/have participated in a study of an investigational agent or is or has been using an investigational device within 4 weeks of the first dose of treatment
- Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
- Had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to prior therapies
- Had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 3 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. - Note: If received major surgery, must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
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 |
|---|---|---|
| PembrolizumabAlso: MK-3475, KEYTRUDA®Pembrolizumab: 200 mg, every (Q) 3 weeks, via intravenous (IV) infusion, until progression or toxicity (or up to 24 months). The first cycle will begin on day 8. | Drug | Combination Therapy |
| PaclitaxelAlso: Taxol, OnxalPaclitaxel: 80 mg/m^2, Q week for 3 weeks, via IV infusion, until progression or toxicity (or complete response if at least 6 cycles, at the discretion of the investigator and participant). Cycle 1 will have an extra lead in week (4 weeks total) with Paclitaxel only on week 1. | Drug | Combination Therapy |
Primary outcome
Progression-free Survival (PFS) at 6 Months
Time frame: 6 months
6-month progression-free survival of the combination of weekly paclitaxel with pembrolizumab (MK-3475) for those patients who received treatment and were evaluable (had one response assessment scan by RECIST 1.1) . 6-month PFS: The proportion of patients at 6 months alive without progressive disease. Progressive Disease (PD): Sum of the longest diameters (SLD) increased by at least 20% from the smallest value on study (including baseline, if that is the smallest).
Occurrence of Adverse Events
Time frame: 2 years, 6 months
Safety of the combination of paclitaxel weekly with pembrolizumab every 3 weeks (Q3W). Serious Adverse Events and Adverse Events will be reported in that Results Data section, according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) V4.0.
4 secondary outcomes
Response Rate (RR)
Time frame: Up to 36 months
Disease Control Rate (DCR)
Time frame: Up to 36 months
Duration of Response (DOR)
Time frame: Up to 36 months
Median Overall Survival (OS)
Time frame: Up to 36 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Oct 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Moffitt Cancer Center Clinical Trials websiteLink provided by the sponsor.
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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.
Robert Wenham, M.D. principal investigator
H. Lee Moffitt Cancer Center and Research Institute
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab and Paclitaxel in people with Ovarian Cancer, run by H. Lee Moffitt Cancer Center and Research Institute 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 16 inclusion and 24 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 7 Oct 2022. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 3 Jun 2021). 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?
Progression-free Survival (PFS) at 6 Months (time frame: 6 months). 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 7 Oct 2022.