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Trial record 88 of 601 for:    Recruiting, Not yet recruiting, Available Studies | Ovarian cancer

PEMBRO With Chemo in Neo Adj Treatment of Ovarian Cancer . (NEOPEMBROV)

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ClinicalTrials.gov Identifier: NCT03275506
Recruitment Status : Not yet recruiting
First Posted : September 7, 2017
Last Update Posted : January 11, 2018
Sponsor:
Information provided by (Responsible Party):
ARCAGY/ GINECO GROUP

Brief Summary:

There are several data suggesting that pembrolizumab and bevacizumab may be synergistic. Enhanced tumor angiogenesis is commonly associated with absence of tumor-infiltrating T cells in patients. There is evidence in OC that tumor expression of VEGF is negatively correlated to the density of CD3+TILs and this phenotype is associated with early recurrence, consistent with prior studies showing a correlation of VEGF to early recurrence and short survival. Furthermore, in ascites, high levels of VEGF correlate to low numbers of NK T-like CD3+CD56+ cells

This randomized phase II study aims to evaluate the efficacy of pembrolizumab in combina-tion with the standard neo adjuvant chemotherapy followed by IDS and the safety of this strategy in patients with advanced ovarian cancer. We assume that its administration in the neo adjuvant setting combination with standard of care (4 cycles of standard chemotherapy) would improve the response rate and consequently will help to achieve optimal debulking rate at IDS.

After surgery, patients will continue to be treated with standard of care (chemotherapy for 2 to 5 cycles plus or less bevacizumab) or the same combination plus pembrolizumab (keytruda).


Condition or disease Intervention/treatment Phase
Ovarian Cancer Stage IV Drug: Pembrolizumab Injectable Product - Chemotherapy - Bev Drug: Chemotherapy - Bev Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: open-label, multicentric
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Open-label, Multicentric Phase II Trial of PEMBROLIZUMAB (Keytruda®) With Chemotherapy Versus Chemotherapy Alone (Standard of Care) as Neo Adjuvant Treatment of Ovarian Cancer Not Amenable to Front Line Debulking Surgery.
Estimated Study Start Date : February 2018
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : September 2022


Arm Intervention/treatment
Experimental: Pembrolizumab + Chemo

Pembrolizumab (ketruda) 200 mg then carboplatin (AUC 5 or 6) and paclitaxel (175mg/m²), q3 weeks.

6 cyles 15 month total

Drug: Pembrolizumab Injectable Product - Chemotherapy - Bev
Pembrolizumab 200 mg then carboplatin (AUC5 or 6) and paclitaxel (175mg/m²), +/- bevacizumab (15 mg/kg Q3W)

Active Comparator: CHEMO alone
carboplatin (AUC5 or 6) and paclitaxel (175mg/m²), q3 weeks. 6 cyles 15 month total
Drug: Chemotherapy - Bev
Carboplatin (AUC5 or 6) and paclitaxel (175mg/m²), +/- bevacizumab (15 mg/kg Q3W)




Primary Outcome Measures :
  1. evaluate the efficacy of neo adjuvant pembrolizumab and chemotherapy or chemo-therapy alone [ Time Frame: 5 years ]

    The primary objective is to evaluate the efficacy of neo adjuvant pembrolizumab and chemotherapy or chemo-therapy alone measured by the complete resection rate after interval debulking surgery. Complete resection will be defined as the removal of all macroscopic residual tumor (CC score = 0)(Appendix 3)

    Hypothesis: Neo adjuvant pembrolizumab in combination with chemotherapy improves the complete resection rate in patients not amenable to upfront debulking surgery.




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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Be willing and able to provide written informed consent/assent for the trial.
  2. Woman 18 and ≤ 75 years old on day of signing informed consent
  3. Histologically confirmed diagnosis of epithelial ovarian carcinoma or fallopian tube carcinoma or primary peritoneal carcinoma with the exception of mucinous histology. Histology should be obtained by laparoscopy (or by laparotomy).
  4. High grade serous or endometrioid (see appendix 1 bis)
  5. Advanced FIGO stage IIIC to IV patient not able to receive primary debulking surgery for which neo adjuvant chemotherapy with carboplatin and paclitaxel is recommended. (primary debulking surgery has been denied after an evaluation through laparoscopy or laparotomy ). Patients with extra abdominal metastasis (FIGO 2014 Stage IV) can be included in case of completely resectable metastasis.
  6. Primary debulking surgery denied but IDS planned with a maximum surgical effort of cytoreduction with the goal of no residual disease.
  7. Eligible for carboplatin and paclitaxel chemotherapy in accordance with local standards of care following cytoreductive surgery.
  8. Interval complete surgery anticipated in a center with excellence.
  9. ECOG performance status (PS) ≤ 2.
  10. Life expectancy of at least 6 months,
  11. Interval between diagnosis and enrolment (informed consent) ≤ 8 weeks,
  12. Be willing to provide blood, and tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 8 weeks (56 days) prior to initiation of treatment on Day 1.
  13. Demonstrate adequate organ function as defined in the table below, all screening labs should be performed within 7 days before randomization.
  14. Adequate hematological laboratory value: Absolute neutrophil count (ANC) : ≥1,500/mm3

    • Platelets : ≥100,000/mm3
    • Hemoglobin : ≥9 g/dL or ≥5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment)
  15. Adequate renal laboratory value:

    • Serum creatinine and Measured or calculated creatinine clearance a (GFR can also be used in place of creatinine or CrCl) ≤1.5 X upper limit of normal (ULN) OR ≥60 mL/min for subject with creatinine levels > 1.5 X institutional ULN (Creatinine clearance is calculated according to Cockcroft formula or to MDRD formula for patients older than 65 years-old. Glomerular filtration rate or creatinine clearance according to MDRD formula is: GFR = 186 x (creatinine (µmol/l) x 0,0113)-1,154 x age- 0,203 x 0.742.)

  16. Adequate hepatic laboratory value:

    • Serum total bilirubin: ≤ 1.5 X ULN OR
    • Direct bilirubin: ≤ ULN for subjects with total bilirubin levels > 1.5 ULN
    • LDH, CRP according local practices
    • AST (SGOT) and ALT (SGPT): ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases
  17. Adequate coagulation laboratory value:

    • 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
  18. Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior randomization. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  19. Female subjects of childbearing potential should be willing to use 1 or 2 methods of birth control or be surgi-cally sterile, or abstain from heterosexual activity for the course of the study through 4 months after the last dose of study medication and 6 months after the last dose of bevacizumab , or paclitaxel, or carboplatin. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year. (see below NB: contraception requirement)
  20. Patient should be beneficiary of healthcare coverage under the social security system.

Exclusion Criteria:

  1. Histological diagnosis of malignant tumor of non-epithelial origin (e.g. germ cell tumor, sex cord-stromal tumor) of the ovary, the fallopian tube or peritoneum or borderline tumor of the ovary (tumor of low malignant potential).
  2. Patients with extra abdominal metastasis (FIGO 2014 Stage IV) not completely resectable, as e.g. multiple parenchymal lung metastases (preferably histologically proven), non resectable lymph node metastases, brain metastases.
  3. Prior systemic therapy for ovarian cancer (e.g. chemotherapy, monoclonal antibody therapy, oral targeted therapy, hormonal therapy),
  4. Prior radiotherapy to the abdomen or prior radiotherapy to an extra-abdominal target volume that would bear the risk of increased toxicity of chemotherapy,
  5. Serious illness or concomitant non-oncological disease such as neurologic, psychiatric or infectious dis-ease, active ulcers (gastrointestinal tract, skin) or a laboratory abnormality that may Increase the risk associated with study participation or study drug administration and in the judgment of the investigator would make the patient inappropriate for entry into the study,
  6. Any contraindications for therapy with paclitaxel or carboplatin, e.g. a history of severe hypersensitivity reactions to paclitaxel or platinum-containing compounds and their excipients, or other drugs formulated with Polyoxyl 35Is 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.
  7. Diagnosis of immunodeficiency or receiving prolonged period of systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
  8. Known history of active Bacillus Tuberculosis (TB)
  9. Hypersensitivity to pembrolizumab or any of its excipients.
  10. Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or no recovery (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
  11. 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 in situ cervical cancer.
  12. Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects 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.
  13. Active autoimmune disease that has required systemic treatment in the 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.
  14. Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
  15. History of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  16. Active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  17. Vaccination with 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., Flu-Mist®) are live attenuated vaccines, and are not allowed.

  18. History of (non-infectious) pneumonitis that required steroids or current pneumonitis.
  19. Active infection requiring systemic therapy.
  20. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  21. Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule,
  22. Psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  23. Active alcohol or drug abuse,
  24. Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 4 months after the last dose of trial treatment, and six months after the last dose of bevacizumab , or paclitaxel, or carboplatin.

    -


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Responsible Party: ARCAGY/ GINECO GROUP
ClinicalTrials.gov Identifier: NCT03275506     History of Changes
Other Study ID Numbers: OV126b
First Posted: September 7, 2017    Key Record Dates
Last Update Posted: January 11, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by ARCAGY/ GINECO GROUP:
neoadjuvant
debulking surgery
Additional relevant MeSH terms:
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Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adnexal Diseases
Genital Diseases, Female
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Paclitaxel
Albumin-Bound Paclitaxel
Carboplatin
Pembrolizumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological