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Pembrolizumab in Combination With Bevacizumab and Pegylated Liposomal Doxorubicin in Patients With Ovarian Cancer (PEMBOV)

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ClinicalTrials.gov Identifier: NCT03596281
Recruitment Status : Not yet recruiting
First Posted : July 23, 2018
Last Update Posted : July 23, 2018
Sponsor:
Information provided by (Responsible Party):
Gustave Roussy, Cancer Campus, Grand Paris

Brief Summary:

French multicenter, open-label, phase 1b, evaluating via the mTPI design the paired treatment of pembrolizumab and PLD (cohort A), pembrolizumab and bevacizumab (cohort B) and finally the combination treatment of the three drugs PLD plus bevacizumab and pembrolizumab (cohort C). Thanks to an expansion cohort C+ the ORR will be evaluated in a total of 19 patients at the RP2 D using an exact binomial one-step Fleming-type design.

Cohort A and B will be opened for inclusions at the same time. Once safety of the dual combinations confirmed in cohorts A and B,cohort C will be opened for inclusions.


Condition or disease Intervention/treatment Phase
Ovarian Cancer Drug: Pembrolizumab Drug: Bevacizumab Drug: pegylated liposomal doxorubicin (PLD) Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Cohort A and B will be opened for inclusions at the same time. Once safety of the dual combinations confirmed in cohorts A and B, cohort C will be opened for inclusions.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label Phase 1 of Pembrolizumab in Combination With Bevacizumab and Pegylated Liposomal Doxorubicin in Patients With Platinum Resistant Epithelial Ovarian Cancer
Estimated Study Start Date : August 2018
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : June 2024


Arm Intervention/treatment
Experimental: Cohort A Drug: Pembrolizumab
200mg Q3W IV

Drug: pegylated liposomal doxorubicin (PLD)
15 or 20 or 30 mg/m² Q3W IV

Experimental: Cohort B Drug: Pembrolizumab
200mg Q3W IV

Drug: Bevacizumab
400 or 300 mg Q3W IV




Primary Outcome Measures :
  1. Dose Limiting Toxicity (DLT) [ Time Frame: Up to 3 weeks ]
    For all the cohorts, the dose limiting toxicity (DLT) period to determine the Maximum dose tolerated (MTD) will be 3 weeks.



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Ages Eligible for Study:   18 Years and older   (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 and to comply with study visits and procedures as per protocol.
  2. Be over 18 years of age on day of signing informed consent.
  3. Histologically confirmed diagnosis of epithelial ovarian carcinoma or fallopian tube carcinoma or primary peritoneal carcinoma.
  4. Have received a front line platinum-based regimen (administered via either IV or IP route) per local standard of care (SOC) or treatment guideline following the primary or interval debulking surgery with documented disease recurrence.

    Note: Maintenance treatment following the front line treatment is permitted and counted together as part of the front line treatment. The absence of debulking for inoperable patients is permitted.

  5. Have fulfilled the following additional requirements regarding prior treatments for recurrent ovarian cancer (ROC). Have received 0 to unlimited additional prior lines for treating ROC and must have a platinum-free interval (PFI) of ≤ 6 months if the last regimen received is a platinum-based.

    Note: PFI is defined as the time elapsed between the last dose of platinum and the documented evidence of disease progression per RECIST 1.1.

  6. Prior therapy containing bevacizumab or other vascular endothelial growth factor (VEGF) pathway-target therapy is permitted.
  7. Have measurable disease (RECIST version 1.1) on ultrasonography and CT scanner without contrast agent and amenable to biopsy.
  8. Have no current clinically relevant bowel obstruction, including sub-occlusive disease, related to underlying disease.
  9. Have no evidence or history of gastro-intestinal events defined as grade≥2, perforation, fistula, necrosis, hemorrhage or intraabdominal abscess.
  10. Have no history or previous treatment of inflammatory bowel disease.
  11. Left ventricular ejection fraction (LVEF) ≥ 50% as determined by gated cardiac radionucleotide scan (MUGA) or echocardiogram. Normal blood pressure (BP) or adequately treated and controlled hypertension (either systolic BP ≤ 140 mmHg and diastolic BP ≤ 90 mmHg). No clinically significant (i.e. active) cardiovascular disease, including: myocardial infarction or unstable angina within ≤ 6 months of inclusion; New York Heart Association (NYHA) ≥grade2 Congestive Heart Failure; poorly controlled cardiac arrhythmia despite medication; peripheral vascular disease grade

    ≥grade3.

  12. Have provided tissue from an archival tissue sample if available (i.e. initial debulking or biopsy).
  13. Eastern Cooperative Oncology Group (ECOG)- performance status 0-2.
  14. Life expectancy ≥ 12 weeks
  15. Demonstrate adequate organ function as defined in Table 2, all screening labs should be performed within 10 days of treatment initiation.
  16. Female subject of childbearing potential should 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.
  17. Female subjects of childbearing potential should 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 6 months after the last dose of study medication (Reference Section 5.9.2).

    Subjects of childbearing potential are those who have not been surgically sterilized (hysterectomy, bilateral oophorectomy or bilateral salpingectomy) or have not been free from menses for > 1 year.

  18. Patient affiliated to a social security system or beneficiary of the same

Exclusion Criteria:

  1. Platinum refractory cancers, defined as lack of response to salvage treatment with a disease recurrence during the first line platinum-based chemotherapy.
  2. Patients with PLD-resistant EOC, as evidenced by lack of response or progression within 6 months of the last dose of PLD.
  3. Administration of other simultaneous chemotherapy drugs, any other anticancer therapy or anti-neoplastic hormonal therapy, or simultaneous radiotherapy during the trial treatment period.
  4. Has had prior chemotherapy, targeted 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.

    Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.

  5. Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of study treatment.
  6. Major surgery within 30 days or bowel resection at cytoreductive surgery within 6 months before the initiation of study treatment.
  7. Non-healing wound or significant traumatic injury within 30 days before the initiation of study treatment.
  8. Any previous radiotherapy to the abdomen or pelvis.
  9. Previous Cerebro-Vascular Accident, Transient Ischaemic Attack or Sub-Arachnoid Haemorrhage.
  10. History or evidence of thrombotic or hemorrhagic disorders within 6 months prior to inclusion.
  11. Prior history of hypertensive crisis or hypertensive encephalopathy.
  12. 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.
  13. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy within 2 years prior to inclusion.
  14. Has known symptomatic 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.
  15. Has an active automimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study.
  16. Has history of (non-infectious) pneumonitis that required steroids, evidence of interstitial lung disease or active non-infectious pneumonitis.
  17. Has an active infection requiring systemic therapy.
  18. Has a Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  19. Has an active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  20. Has a 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. Is pregnant or breastfeeding, or expecting to conceive within the projected duration of the trial, starting with the pre-screening or screening visit through 6 months after the last dose of trial traetment
  22. Has 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 (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
  23. Has received a live vaccine within 30 days prior to the first dose of trial treatment.
  24. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  25. Patient under guardianship or deprived of his liberty by a judicial or administrative decision
  26. Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is investigational site or sponsor staff directly involved with this trial, unless prospective ethic approval (by chair or designee) is given allowing exception to this criterion for a specific subject.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03596281


Contacts
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Contact: Judith MICHELS, MD, PhD 0142114376 ext +33 judith.michels@gustaverousy.fr
Contact: Xavier PAOLETTI, MD 0142116564 ext +33 xavier.paoletti@gustaveroussy.fr

Locations
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France
Gustave Roussy Active, not recruiting
Villejuif, Val De Marne, France, 94805
Sponsors and Collaborators
Gustave Roussy, Cancer Campus, Grand Paris

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Responsible Party: Gustave Roussy, Cancer Campus, Grand Paris
ClinicalTrials.gov Identifier: NCT03596281     History of Changes
Other Study ID Numbers: 2017-004197-34
2016/2456 ( Other Identifier: CSET number )
First Posted: July 23, 2018    Key Record Dates
Last Update Posted: July 23, 2018
Last Verified: July 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
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
Bevacizumab
Pembrolizumab
Doxorubicin
Liposomal doxorubicin
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors