Clinical Trials /

Combination Pembrolizumab, Chemotherapy and Bevacizumab in Patients With Cervical Cancer

NCT03367871

Description:

The investigators propose to evaluate the efficacy of the combination of standard chemotherapy with bevacizumab with Pembrolizumab in women with recurrent, persistent, or metastatic cervical cancer.

Related Conditions:
  • Cervical Adenocarcinoma
  • Cervical Adenosquamous Carcinoma
  • Cervical Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Combination Pembrolizumab, Chemotherapy and Bevacizumab in Patients With Cervical Cancer
  • Official Title: Phase II Single Arm Study of Combination Pembrolizumab, Chemotherapy and Bevacizumab in Patients With Recurrent, Persistent, or Metastatic Cervical Cancer

Clinical Trial IDs

  • ORG STUDY ID: 20170846
  • NCT ID: NCT03367871

Conditions

  • Cervical Cancer

Interventions

DrugSynonymsArms
PembrolizumabMK-3475, KeytrudaPembrolizumab, Chemotherapy, Bevacizumab
PaclitaxelTaxolPembrolizumab, Chemotherapy, Bevacizumab
CisplatinPlatinolPembrolizumab, Chemotherapy, Bevacizumab
CarboplatinParaplatinPembrolizumab, Chemotherapy, Bevacizumab
BevacizumabAvastinPembrolizumab, Chemotherapy, Bevacizumab

Purpose

The investigators propose to evaluate the efficacy of the combination of standard chemotherapy with bevacizumab with Pembrolizumab in women with recurrent, persistent, or metastatic cervical cancer.

Detailed Description

      This is a single arm, open-label, phase II study to assess progression free survival in
      patients treated with pembrolizumab, chemotherapy, and bevacizumab for recurrent, persistent,
      or metastatic cervical cancer. Progression free survival will be assessed in patients treated
      with this combination.

      Eligible patients will require tissue biopsy for diagnostic confirmation of metastatic
      disease, disease recurrence or persistence. Patients will be treated with 3 cycles of
      combination therapy. A cycle will consist of pembrolizumab at 200mg (IV), paclitaxel 175mg/m2
      or 135mg/m2 (IV), cisplatin 50mg/m2 (or carboplatin AUC 5) and bevacizumab 15mg/kg , on day 1
      every 21 days. The length of a cycle is 21 days. If disease remains following 3 cycles, a
      second biopsy may be obtained. Imaging will be obtained after every 3 cycles to assess for
      disease response. Blood collection will be performed before and after pembrolizumab treatment
      and at end of study.

      Thirty-nine subjects will be accrued and treated at Sylvester Comprehensive Cancer Center
      (SCCC)/University of Miami Hospital (UMH) inclusive of its satellite sites, and Jackson
      Memorial Hospital for approximately 24 months. Therapy will be administered until study
      completion, withdrawal of consent, disease progression and/or unacceptable toxicity,
      whichever occurs first.

      All subjects will be followed for a Safety Evaluation at approximately 30-days (+7 days)
      after the last dose of study treatment or before the initiation of a new anti-cancer
      treatment, whichever occurs first. Thereafter subjects will be followed every 3-months for up
      to 24 months from the treatment discontinuation for survival data only.
    

Trial Arms

NameTypeDescriptionInterventions
Pembrolizumab, Chemotherapy, BevacizumabExperimentalOn day 1 of each 21 day cycle - Pembrolizumab 200mg (IV), Paclitaxel 175mg/m2 or 135 mg/m2 (IV), and Cisplatin 50mg/m2 (IV) or Carboplatin AUC 5, Bevacizumab 15mg/kg (IV)
  • Pembrolizumab
  • Paclitaxel
  • Cisplatin
  • Carboplatin
  • Bevacizumab

Eligibility Criteria

        Inclusion Criteria:

          1. Patients must have histologically confirmed recurrent, persistent or metastatic
             (primary stage IVB) squamous cell carcinoma, adenosquamous carcinoma or adenocarcinoma
             of the cervix that is not amenable to curative treatment with surgery and/or radiation
             therapy.

          2. All patients must have measurable disease as defined by Response Evaluation Criteria
             In Solid Tumors (RECIST) 1.1.

          3. Patients must have recovered from effects of recent surgery or radiotherapy or
             chemoradiotherapy.

          4. Patients should be free of active infections requiring antibiotics (with the exception
             of uncomplicated urinary tract infection).

          5. Tissue from an archival sample or newly obtained core or excisional biopsy of a tumor
             lesion within 6 weeks confirming diagnosis.

          6. Age ≥ 18 years

          7. Life expectancy > 3 months

          8. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

          9. Patients must have normal organ and marrow function as defined below:

               -  Absolute neutrophil count (ANC) ≥1,500 /mcL

               -  Platelets ≥ 100,000 / mcL

               -  Hemoglobin ≥ 8 g/dL or ≥ 5.6 mmol/L without transfusion or erythropoietin (EPO)
                  dependency

               -  Serum creatinine ≤ 1.5 X upper limit of normal (ULN) OR Measured or calculated a
                  creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≥ 60
                  mL/min for subject with creatinine levels > 1.5 X institutional ULN. Creatinine
                  clearance should be calculated per institutional standard.

               -  Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with
                  total bilirubin levels > 1.5 ULN

               -  Aspartate transaminase (AST) (SGOT) and alanine transaminase (ALT) (SGPT) ≤ 2.5 X
                  ULN OR ≤ 5 X ULN for subjects with liver metastases

               -  Albumin ≥ 2.5 mg/dL

               -  International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 X ULN unless
                  subject is receiving anticoagulant therapy as long as PT or PTT is within
                  therapeutic range of intended use of anticoagulants.

               -  Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 X ULN unless subject is
                  receiving anticoagulant therapy as long as PT or PTT is within therapeutic range
                  of intended use of anticoagulants.

         10. Negative urine or serum pregnancy ≤72 hours (i.e. 3 days) prior to receiving the first
             dose of study medication if not surgically sterilized. If the urine test is positive
             or cannot be confirmed as negative, a serum pregnancy test will be required.

         11. Female subjects of childbearing potential (have not been surgically sterilized or have
             not been without menses for >1 year) should be willing to use 2 methods of birth
             control at the same time or be surgically sterile, or abstain from heterosexual
             activity

         12. Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria:

          1. Patients with a history of other invasive malignancies, with the exception of
             nonmelanoma skin cancer, are ineligible if there is any evidence of other malignancy
             being present within the last 5 years.

          2. Patients who have had prior chemotherapy except when used concurrently with radiation
             therapy.

          3. Patients who have received prior radiotherapy to any portion of the abdominal cavity
             or pelvis other than for the treatment of cervical cancer within the last 5 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.

          4. Patients with an ECOG performance status of 2, 3 or 4.

          5. Has received prior therapy with an anti-PD1, anti-PDL1, or anti-PDL2 agent.

          6. Patients with known active central nervous system (CNS) metastases and/or
             carcinomatous meningitis.

          7. Patients with a known sensitivity to humanized antibodies or sensitivity attributed to
             compounds of similar chemical or biologic composition to platinum based chemotherapy
             or paclitaxel (not responsive to traditional desensitization procedures).

          8. Patients with a known history of human immunodeficiency virus (HIV), active bacillus
             tuberculosis (TB), or have received a live virus vaccine within 30 days prior to the
             first dose of study treatment.

          9. Known psychiatric or substance abuse disorders that would interfere with cooperation
             with requirements of the study

         10. Has active autoimmune disease that has required systemic treatment in the past two
             years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
             drugs). Replacement therapy (i.e. thyroxine, insulin, or physiologic corticosteroid
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
             form of systemic treatment.

         11. History of non-infectious pneumonitis that required steroids, evidence of interstitial
             lung disease or active, non-infectious pneumonitis, or history of pneumonitis
             requiring treatment.

         12. Is pregnant or breastfeeding or expecting to conceive within the projected duration of
             the study, starting with the pre-screening or screening visit through 120 days after
             the last dose of study treatment.

         13. Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
             [qualitative] is detected).

         14. Received live vaccine within 30 days prior to the first dose of study treatment. Note:

             Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
             are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live
             attenuated vaccines, and are not allowed.

         15. Patient with known hypersensitivity to pembrolizumab or any of its excipients (active
             ingredients).

         16. Patient receiving concurrent additional biologic therapy.

         17. History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to cisplatin and/or paclitaxel not responsive to traditional
             desensitization procedures.

         18. Any other serious medical or psychiatric illness/condition, in the judgment of the
             Investigator(s), is likely to interfere or limit compliance with study
             requirements/treatment.

         19. Patients who are adults and unable to consent, who are not yet adults, pregnant and
             nursing women, and prisoners are ineligible.

         20. Any other serious medical or psychiatric illness/condition likely in the judgment of
             the Investigator(s) to interfere or limit compliance with study
             requirements/treatment.

         21. Has an active infection requiring systemic therapy.

         22. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
             other form of immunosuppressive therapy within 7 days prior to planned first dose of
             the study. The use of physiological doses of corticosteroids may be approved after
             consultation with the PI.

         23. Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling, or
             child who is an investigational site or sponsor staff directly involved with this
             trial, unless prospective institutional review board (IRB) approval (by chair or
             designee) is given, allowing exception to this criterion.

         24. Thromboembolism (either arterial or venous) within 6 weeks of initiation of treatment.

         25. Have significant cardiovascular disease, such as New York Heart Association cardiac
             disease (Class II or greater), myocardial infarction, or cerebrovascular accident
             within 3 months prior to initiation of study treatment, unstable arrhythmias, or
             unstable angina. Patients with known coronary artery disease, congestive heart failure
             not meeting the above criteria, or left ventricular ejection fraction <50% must be on
             a stable medical regimen that is optimized in the opinion of the treating physician,
             in consultation with a cardiologist if appropriate.

         26. Undergo major surgical procedure within 28 days prior to first bevacizumab dose or
             anticipation of the need for a major surgical procedure during the course of the
             study.

         27. Have proteinuria, as demonstrated by urine dipstick or >1.0g of protein in a urine
             protein-to-creatinine ratio and/or 24hr urine collection. All patients with ≥2+
             protein on dipstick urinalysis at baseline must undergo a urine-to-protein ration
             and/or 24hr urine collection and demonstrate <1.0g of protein
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:Up to 24 months
Safety Issue:
Description:Objective response defined as complete or partial

Secondary Outcome Measures

Measure:Progression-Free Survival (PFS) Rate
Time Frame:Up to 24 months
Safety Issue:
Description:Rate of Progression-Free Survival (PFS) in study participants.
Measure:Overall Survival (OS) Rate
Time Frame:Up to 24 months
Safety Issue:
Description:Rate of Overall Survival (OS)

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Miami

Trial Keywords

  • Recurrent Cervical Cancer
  • Persistent Cervical Cancer
  • Metastatic Cervical Cancer

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