Tri Association in Patient With Advanced Epithelial Ovarian Cancer in Relapse

NCT04015739 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: GINECO OV 238
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 9

Brief Summary

Assessing the safety and efficacy of the bevacizumab, Olaparib and Durvalumab (MEDI 4736) combination in patient with high grade serous or high grade endometrioid or other high grade epithelial non mucinous ovarian tumor, with at least one previous line of platinum-taxane chemotherapy, and present with platinum resistant disease (PRR) or platinum-sensitive relapse (PSR), whatever the line of chemotherapy given at relapse.

Conditions

Epithelial Ovarian Cancer; Relapse

Keywords

Bevacizumab; Olaparib; Durvalumab; Tri association

Outcome Measures

Primary Outcomes (2)

• Safety and tolerability of the PRR cohort: Rate of clinical and radiological non-progressive disease

  Rate of clinical and radiological non-progressive disease, as assessed by immune-related response criteria (irRC) at 3 months

  At 3 months

• Safety and tolerability of the PSR cohort: Rate of clinical and radiological non-progressive disease

  Rate of clinical and radiological non-progressive disease, as assessed by immune-related response criteria (irRC) at 6 months

  At 6 months

Secondary Outcomes (5)

• CA 125 change as expressed by the KELIM parameter

  up to 60 months

• Progression free survival (PFS)

  up to 60 months

• Overall survival (OS)

  up to 60 months

• Tumor response

  up to 60 months

• Toxicity as assessed by CTCAE V.5.0 scale

  up to 60 months

Other Outcomes (3)

• Translational research objectives n°1: Correlation between increase of Tumour Mutational Burden (TMB) after 6 weeks of treatment and response to the treatment combination.

  up to 60 months

• Translational research objectives n°2: Correlation between Homologous recombination (HR) status at baseline and response to the treatment combination.

  up to 60 months

• Translational research objectives n°3: Correlation between tumour immune infiltrate and Immune Check Point (ICP) status at baseline and response to the association.

  up to 60 months

Study Arms (1)

Bevacizumab, Olaparib and Durvalumab

EXPERIMENTAL

Single arm study

Drug: Bevacizumab, Olaparib and Durvalumab (MEDI 4736) combination

Interventions

Bevacizumab, Olaparib and Durvalumab (MEDI 4736) combination DRUG

Patients will receive a combination of these 3 drugs : Bevacizumab 15mg/kg q3w IV, Olaparib 300mg BD Per Os; and Durvalumab (MEDI 4736) 1.12g IV q3w

Also known as: Experimental treatment

Bevacizumab, Olaparib and Durvalumab

Eligibility Criteria

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

You may qualify if:

• Patients with platinum resistant relapse
• Female Patient must be ≥18 years of age.
• Signed informed consent and ability to comply with treatment and follow-up.
• Patient with Ovarian cancer, primary peritoneal cancer and/or fallopian-tube cancer, histologically confirmed (based on local histopathological findings): high grade serous or high grade endometrioid or other high grade epithelial non mucinous ovarian tumor.
• Patient who has completed at least one line of platinum-taxane chemotherapy, and presents with platinum resistant relapse (resistant disease defined by a tumor progression less than six months after the last dose of platinum) \[Note: the patient may have received one or even more line of platinum based chemotherapy\] OR Patient who is in platinum-sensitive relapse, whatever the line of chemotherapy given at relapse \[Note: any chemotherapy previously administered must have contained a platinum compound\]. The platinum sensitive relapse is defined by a tumor progression occurring more than six months after the last dose of platinum chemotherapy.
• Patient who didn't receive any of the tested drugs, or previously received either bevacizumab or olaparib BUT NOT the combination of both drugs.
• At least one measurable or evaluable lesion that can be accurately assessed at baseline by computed tomography (CT) (or magnetic resonance imaging \[MRI\] where CT is contraindicated) and is suitable for repeated assessment as per irRC. The baseline scan must be obtained within 28 days of first dose.
• Patient not amenable to cytoreductive surgery at the time of relapse (surgery is not allowed during the protocole treatment).
• Patient must have normal organ and bone marrow function:
• Hemoglobin ≥ 10.0 g/dL. (Transfusions is not allowed within 28 days before randomization)
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L.
• Platelet count ≥ 100 x 109/L. (Platelet transfusion or G-CSF administration is not allowed within 28 days before randomization)
• Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN).
• Aspartate aminotransferase / Serum Glutamic Oxaloacetic Transaminase (ASAT/SGOT)) and Alanine aminotransferase / Serum Glutamic Pyruvate Transaminase (ALAT/SGPT)) ≤ 2.5 x ULN, unless liver metastases are present in which case they must be ≤ 5 x ULN.
• Creatinine clearance ≥ 60 mL/min by Cockcroft and Gault formula.

You may not qualify if:

• Non-epithelial origin of the tumor (i.e. germ cell tumor).
• Ovarian tumors of low malignant potential (e.g. borderline tumors), or mucinous carcinoma.
• Carcinosarcoma (Mixed Mullerian Tumor)
• Patient with synchronous primary endometrial cancer unless both of the following criteria are met:
• Stage \< II,
• Less than 60 years old at the time of diagnosis of endometrial cancer with stage IA or IB grade 1 or 2, or stage IA grade III endometrial carcinoma,OR ≥ 60 years old at the time of diagnosis of endometrial cancer with stage IA grade 1 or 2 endometrioid adenocarcinoma.
• Patient with serous or clear cell adenocarcinoma or carcinosarcoma of the endometrium is not eligible.
• Other malignancy within the last 5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS). Patient with a history of localized malignancy diagnosed over 5 years ago may be eligible provided she completed her adjuvant systemic therapy and remains free of recurrent or metastatic disease. Patient with history of primary triple negative breast cancer may be eligible provided she completed her definitive anticancer treatment more than 3 years ago and she remains breast cancer disease free prior to start of study treatment.
• Patient with myelodysplastic syndrome/acute myeloid leukemia history.
• Current or prior use of immunosuppressive medication within 14 days (use 28 days if combining durvalumab with a novel agent) before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. (...)
• Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). (...)
• Patient receiving radiotherapy within 6 weeks prior to study treatment.
• Major surgery within 4 weeks of starting study treatment and patient must have recovered from any effects of any major surgery.

Sponsors & Collaborators

• ARCAGY/ GINECO GROUP: lead

Study Sites (9)

Institut Bergonié

Bordeaux, 33076, France

Location

Centre Oscar Lambret

Lille, 59000, France

Location

Centre Léon Bérard

Lyon, 69008, France

Location

ICM Val d'Aurelle

Montpellier, 34298, France

Location

Groupe Hospitalier des Diaconesses Croix Saint-Simon

Paris, 75960, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

Institut Curie - Site Saint Cloud

Saint-Cloud, 92210, France

Location

Institut Claudius Régaud

Toulouse, 31059, France

Location

Gustave Roussy

Villejuif, 94805, France

Location

MeSH Terms

Conditions

Carcinoma, Ovarian Epithelial; Recurrence

Interventions

Bevacizumab; olaparib; durvalumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Ovarian Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; 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; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Study Officials

• Gilles Freyer

  Centre Hospitalier Lyon Sud

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients will be treated the same way in the PRR and PSR cohorts: Durvalumab 1.12 g IV on Day 1 Q3W Bevacizumab 15 mg/kg Day 1 Q3W Olaparib 300 mg bid po, continuously Patients will be treated upon disease progression, unacceptable toxicity or consent withdrawal.

Study Record Dates

• First Submitted: January 2, 2019
• First Posted: July 11, 2019
• Study Start: March 1, 2019
• Primary Completion: June 30, 2020
• Study Completion: January 29, 2024
• Last Updated: August 17, 2022

Record last verified: 2022-08

Locations

FR (9)