Pembrolizumab in Combination with Bevacizumab and Pegylated Liposomal Doxorubicin in Patients with Ovarian Cancer

NCT03596281 | Completed Phase 1

• 2 other identifiers: 2017-004197-342016/2456
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

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.

Conditions

Ovarian Cancer

Outcome Measures

Primary Outcomes (1)

• Dose Limiting Toxicity (DLT)

  For all the cohorts, the dose limiting toxicity (DLT) period to determine the Maximum dose tolerated (MTD) will be 3 weeks.

  Up to 3 weeks

Study Arms (2)

Cohort A

EXPERIMENTAL

Drug: Pembrolizumab; Drug: pegylated liposomal doxorubicin (PLD)

Cohort B

EXPERIMENTAL

Drug: Pembrolizumab; Drug: Bevacizumab

Interventions

Pembrolizumab DRUG

200mg Q3W IV

Cohort A; Cohort B

Bevacizumab DRUG

400 or 300 mg Q3W IV

Cohort B

pegylated liposomal doxorubicin (PLD) DRUG

15 or 20 or 30 mg/m² Q3W IV

Cohort A

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing and able to provide written informed consent/assent for the trial and to comply with study visits and procedures as per protocol.
• Be over 18 years of age on day of signing informed consent.
• Histologically confirmed diagnosis of epithelial ovarian carcinoma or fallopian tube carcinoma or primary peritoneal carcinoma.
• 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.
• 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.
• Prior therapy containing bevacizumab or other vascular endothelial growth factor (VEGF) pathway-target therapy is permitted.
• HMeasurable disease (RECIST version 1.1) by investigator assessment with at least 1 unidimensional measurable lesion
• At least one lesion amenable to biopsy, visible by imaging or without radiological guidance (e.g. vaginal lesion
• Have no evidence or history of gastro-intestinal events defined as grade≥2, perforation, fistula, necrosis, hemorrhage or intraabdominal abscess.
• Have no history or previous treatment of inflammatory bowel disease.
• ≥grade3.
• Have provided tissue from an archival tissue sample if available (i.e. initial debulking or biopsy).
• Eastern Cooperative Oncology Group (ECOG)- performance status 0-1.

You may not qualify if:

• Platinum refractory cancers, defined as lack of response to salvage treatment with a disease recurrence during the first line platinum-based chemotherapy.
• Patients with PLD-resistant EOC, as evidenced by lack of response or progression within 6 months of the last dose of PLD.
• Administration of other simultaneous chemotherapy drugs, any other anticancer therapy or anti-neoplastic hormonal therapy, or simultaneous radiotherapy during the trial treatment period.
• 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.
• 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.
• Major surgery within 30 days or bowel resection at cytoreductive surgery within 6 months before the initiation of study treatment.
• Non-healing wound or significant traumatic injury within 30 days before the initiation of study treatment.
• Any previous radiotherapy to the abdomen or pelvis.
• Previous Cerebro-Vascular Accident, Transient Ischaemic Attack or Sub-Arachnoid Haemorrhage.
• Prior history of hypertensive crisis or hypertensive encephalopathy.
• 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.
• 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.
• Has an active autoimmune 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.
• Has history of (non-infectious) pneumonitis that required steroids, evidence of interstitial lung disease or active pneumonitis.

Sponsors & Collaborators

• Gustave Roussy, Cancer Campus, Grand Paris: lead

Study Sites (1)

Gustave Roussy

Villejuif, Val de Marne, 94805, France

Location

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

pembrolizumab; Bevacizumab; liposomal doxorubicin

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: June 15, 2018
• First Posted: July 23, 2018
• Study Start: December 5, 2018
• Primary Completion: March 11, 2021
• Study Completion: April 11, 2023
• Last Updated: October 18, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)