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Fallopian Tube Clear Cell AdenocarcinomaPhase 2NCT02853318

Pembrolizumab, Bevacizumab, and Cyclophosphamide in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

A Phase 2 study testing Bevacizumab, Cyclophosphamide and Laboratory Biomarker Analysis in people with Fallopian Tube Clear Cell Adenocarcinoma and Fallopian Tube Endometrioid Adenocarcinoma, run by Roswell Park Cancer Institute at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This phase II trial studies the combination of pembrolizumab, bevacizumab, and low dose oral cyclophosphamide in treating patients with recurrent ovarian, fallopian tube, or primary peritoneal cancer. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Bevacizumab, Cyclophosphamide and Laboratory Biomarker Analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
1 siteUnited States
Study dates
1 Sep 2016to 30 Jun 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
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Have measurable disease per RECIST 1.1 criteria present
  • Participant may have serous, endometrioid, clear cell, mucinous or undifferentiated type of recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer
  • Histologic confirmation of the original primary tumor is required via the pathology report
  • Participant can be either platinum-sensitive (platinum free interval [PFI] >= 6 months prior to recent recurrence) or platinum-resistant (PFI < 6 months prior to recent recurrence). If the participant has a platinum sensitive disease, she may only enroll in this clinical trial if there is a contraindication for her to receive further treatment with platinum-based chemotherapy (such as serious, persistent toxicity or sever hypersensitivity to platinum agents or she declines standard of care).
  • Participant must be willing to undergo core or excisional biopsy of a tumor lesion within 4 weeks (28 days) prior to initiation of treatment on day 1 and after 3 cyles of study treatment; participants for whom newly obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the principal investigator
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  • Absolute neutrophil count (ANC): >= 1,500 /mcL
  • Platelets: >= 100,000 / mcL
  • Hemoglobin: >= 9 g/dL or 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
  • Serum creatinine: =< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance >= 60 mL/min for participant with creatinine levels > 1.5 X institutional ULN; glomerular filtration rate (GFR) can also be used in place of creatinine or creatinine clearance (CrCl)
  • Urine protein creatine ratio (UPCR) < 1 prior to enrollment
  • Serum total bilirubin: =< 1.5 X ULN OR direct bilirubin =< ULN for participants with total bilirubin levels > 1.5 ULN
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase[SGOT]) and alanine transaminase (ALT) (serum glutamic pyruvic transaminase [SGPT]): =< 2.5 X ULN OR =< 5 X ULN for participants with liver metastases
  • Albumin: > 2.5 mg/dL
  • International normalized ratio (INR) or prothrombin time (PT): =< 1.5 unless participant is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
  • Activated partial thromboplastin time (aPTT): =< 1.5 X ULN unless participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • Participants of childbearing potential must have a 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
  • Participants of childbearing potential must be 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 (participants of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year); should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately
  • Participant has recovered from toxicities of prior chemotherapy or other therapy (to grade 2 or less)
  • Participant may have received prior investigational therapy (including immune therapy)
  • Participant may have received prior hormonal therapy
  • Participant may have received bevacizumab (or other antiangiogenic agent) and/or cyclophosphamide in the past
  • Participant has had at least 4 weeks of postoperative recovery from surgery prior to enrollment to ensure complete wound healing; participants with bowel resections at surgery should begin protocol at least 42 days after surgery
  • Ability to swallow and retain oral medication
  • Participant or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Who cannot join

  • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
  • Has a 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 or, is taking any other medication that might affect immune function
  • Has a known history of active bacillus tuberculosis (TB)
  • Hypersensitivity to bevacizumab, cyclophosphamide, pembrolizumab or any of its excipients
  • Has had a prior anti-cancer monoclonal antibody (mAb) 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 agents administered more than 4 weeks earlier
  • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 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
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  • Note: participants with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study
  • Note: if participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy and, has to be at least 28 days after the surgery
  • Has a known additional malignancy that is progressing or requires active treatment: exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or cervical cancer in situ that has undergone potentially curative therapy
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; participants with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four 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; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
  • Has active autoimmune disease that has required systemic treatment in the past 6 months (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) is not considered a form of systemic treatment
  • Has known history of, or any evidence of active, non-infectious pneumonitis
  • Has an active infection requiring systemic therapy
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Is pregnant or breastfeeding, or expecting to conceive 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
  • Has received prior therapy with an anti-PD-1, anti-programmed cell death 1 ligand 1 (PD-L1), or anti-programmed cell death 1 ligand 2 (PD-L2) agent
  • Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
  • Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
  • Has received a live vaccine within 30 days of planned start of study therapy
  • Note: seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines, and are not allowed
  • Active or history of inflammatory bowel disease (colitis, Crohn's), diverticulitis, irritable bowel disease, celiac disease, or other serious, chronic, gastrointestinal conditions associated with diarrhea; active or history of systemic lupus erythematosus or Wegener's granulomatosis
  • Participant has clinical symptoms or signs of partial or complete gastrointestinal obstruction or, requires parenteral hydration and/or nutrition
  • Participant requires, or is likely to require, more than a two-week course of corticosteroids for intercurrent illness; participant must complete the course of corticosteroids 2 weeks before screening to meet eligibility
  • Participant has a serious, non-healing wound, ulcer, or bone fracture
  • Participant has a clinically significant cardiovascular disease including:
  • Uncontrolled hypertension, defined as systolic > 150 mmHg or diastolic > 90 mmHg
  • Myocardial infarction or unstable angina within 6 months prior to enrollment
  • New York Heart Association (NYHA) grade II or greater congestive heart failure
  • Participant has a grade II or greater peripheral vascular disease
  • Participant has a clinically significant peripheral artery disease (e.g. those with claudication, within 6 months)
  • Participant has organ allografts
  • Participant is receiving medication(s) that might affect immune function
  • Unwilling or unable to follow protocol requirements

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

Other trials in United States

About this study

Official title: A Phase II Evaluation of Pembrolizumab in Combination With IV Bevacizumab and Oral Metronomic Cyclophosphamide in the Treatment of Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

This phase II trial studies the combination of pembrolizumab, bevacizumab, and low dose oral cyclophosphamide in treating patients with recurrent ovarian, fallopian tube, or primary peritoneal cancer. Monoclonal antibodies, such as pembrolizumab and bevacizumab, may block tumor growth in different ways such as boosting your own immune system to find, recognize and kill tumor cells as well as by blocking the growth of new blood vessels necessary for tumor growth and nutrition. Drugs used in chemotherapy, such as low dose oral cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells, as well as by further enhancing your own body's immune response against cancer cells. As these three drugs have all been shown to improve the immune response against cancer cells giving pembrolizumab, bevacizumab, and cyclophosphamide together may work better in treating patients with recurrent ovarian, fallopian tube, or primary peritoneal cancer.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate improvement in progression-free survival for patients treated with anti-programmed cell death 1 (anti-PD1) pembrolizumab in combination with intravenous (IV) bevacizumab and oral metronomic cyclophosphamide as compared to patients treated with other second line chemotherapeutic agents.

SECONDARY OBJECTIVES:

  1. To obtain pilot data on clinical response rates using both Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria and immune related response criteria (irRECIST).

II. To obtain data on changes in tumor microenvironment prior to and subsequent to therapy and, to screen for potential biomarkers to predict clinical benefit.

III. To determine the safety and tolerability of the treatment combination in the study population.

IV. To evaluate overall survival in patients treated with anti-PD1 pembrolizumab in combination with IV bevacizumab and oral metronomic cyclophosphamide.

  1. To assess the impact of the combination of anti-PD1 pembrolizumab, IV bevacizumab and oral metronomic cyclophosphamide on anti-tumor immune responses in ovarian cancer.

OUTLINE:

Patients receive pembrolizumab IV over 30 minutes and bevacizumab IV over 30-90 minutes on day 1 and cyclophosphamide orally (PO) once daily (QD) on days 1-21. Treatment repeats every 3 weeks for up to 12 months (or 17 courses) in the absence of disease progression or unacceptable toxicity. Patients without evidence of disease progression may continue treatment in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, then every 3 months for 1 year, and every 12 weeks and 6 months thereafter.

Being tested
Bevacizumab, Cyclophosphamide, Laboratory Biomarker Analysis, Pembrolizumab
Medical subject headings
Fallopian Tube Neoplasms, Ovarian Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BevacizumabBiological

    Also called Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin

    Given IV

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • PembrolizumabBiological

    Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475

    Given IV

Study groups in NCT02853318
Study groupRoleWhat they receive
Treatment (pembrolizumab, bevacizumab, cyclophosphamide)ExperimentalPatients receive pembrolizumab IV over 30 minutes and bevacizumab IV over 30-90 minutes on day 1 and cyclophosphamide PO QD on days 1-21. Treatment repeats every 3 weeks for up to 17 courses in the absence of disease progression or unacceptable toxicity. Patients without evidence of disease progression may continue treatment in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Bevacizumab; Drug: Cyclophosphamide; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of Adverse Events Assessed by Common Terminology Criteria for Adverse Events

    The highest observed adverse event will be tabulated by grade across all dose levels and cycles.

    Measured: Up to 1 year

  2. Progression-free Survival (PFS)

    Will be summarized using standard Kaplan-Meier methods, with estimates of median survival and given survival rates will be obtained with 90% confidence intervals.

    Measured: Time from the start of the study treatment until PFS event, assessed up to 1 year after the last subject enrolls

Secondary outcomes (3)

  1. Duration of Overall Survival

    Will be summarized using standard Kaplan-Meier methods, with estimates of median survival and given survival rates will be obtained with 90% confidence intervals.

    Measured: Up to 1 year after enrollment of the last subject

  2. An Anti-tumor Immune Response in Circulation and Tumor Tissue

    Assessed with immunohistochemistry (IHC), Nannostring, Flow Cytometry and Luminex assay.

    Measured: Up to 1 year

  3. Objective Tumor Response Assessed by Modified RECIST Version 1.1 Criteria

    Frequency of response will be summarized with a 90% confidence interval.

    An objective response is defined as a CR or PR, while a non-responder is defined as a SD or PD.

    Measured: Up to 6 months after enrollment start of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Aug 2016 (estimated)
  2. Study start1 Sep 2016
  3. Primary completion27 Jun 2019
  4. Study completion30 Jun 2021

Resources

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
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02853318
Sponsor's protocol ID
I 270715
Other IDs
NCI-2016-00534, I 270715
Status last verified
Sep 2021
First submitted
29 Jul 2016
Last updated
6 Oct 2021
Data monitoring committee
Yes

Publications

  • Rosario SR, Long MD, Chilakapati S, Gomez EC, Battaglia S, Singh PK, Wang J, Wang K, Attwood K, Hess SM, McGray AJR, Odunsi K, Segal BH, Paragh G, Liu S, Wargo JA, Zsiros E. Integrative multi-omics analysis uncovers tumor-immune-gut axis influencing immunotherapy outcomes in ovarian cancer. Nat Commun. 2024 Dec 5;15(1):10609. doi: 10.1038/s41467-024-54565-8.

    PubMed 39638782

  • Zsiros E, Lynam S, Attwood KM, Wang C, Chilakapati S, Gomez EC, Liu S, Akers S, Lele S, Frederick PJ, Odunsi K. Efficacy and Safety of Pembrolizumab in Combination With Bevacizumab and Oral Metronomic Cyclophosphamide in the Treatment of Recurrent Ovarian Cancer: A Phase 2 Nonrandomized Clinical Trial. JAMA Oncol. 2021 Jan 1;7(1):78-85. doi: 10.1001/jamaoncol.2020.5945.

    PubMed 33211063

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bevacizumab, Cyclophosphamide and Laboratory Biomarker Analysis in people with Fallopian Tube Clear Cell Adenocarcinoma and Fallopian Tube Endometrioid Adenocarcinoma, run by Roswell Park Cancer Institute at 1 site 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 25 inclusion and 34 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 6 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 6 Nov 2020). 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?

Incidence of Adverse Events Assessed by Common Terminology Criteria for Adverse Events (time frame: Up to 1 year). 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?

On the ClinicalTrials.gov record for NCT02853318, which also lists 2 linked publications.

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 6 Oct 2021.

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