A Phase II Study of Neoadjuvant Chemotherapy Plus Durvalumab (MEDI4736) and Tremelimumab in Advanced-stage Ovarian Cancer (TRU-D)

NCT03899610 | Unknown Phase 2 DMC

• 3 other identifiers: 4-2019-0083KGOG3046ESR-17-13142
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 4

Brief Summary

The primary objective of this trial is to evaluate the synergistic effects of durvalumab and tremelimumab plus chemotherapy in advanced-stage ovarian cancer. Ovarian cancer is the deadliest gynecologic cancer. The current standard therapy is surgical cytoreduction followed by taxane-platinum combination chemotherapy. However, most patients with advanced-stage ovarian cancer will experience a relapse of disease. Therefore, there is an urgent need to improve outcomes of patients with this aggressive cancer. Research hypothesis: Adding durvalumab and tremelimumab to current neoadjuvant chemotherapy (front-line therapy) in advanced-stage ovarian cancer can increase response rate and improve patient's outcome such as progression-free survival and overall survival with minimal effects on safety.

Conditions

Ovarian Cancer Stage IIIC; Ovarian Cancer Stage IV

Keywords

TRU-D

Outcome Measures

Primary Outcomes (1)

• Progression-free survival(PFS)

  12-months progression-free survival rate will be estimated, and 95% confidence intervals will be calculated.

  12 months

Secondary Outcomes (7)

• Response rate

  9 weeks

• Immune-related response

  9 weeks

• Response rate by PERCIST

  9 weeks

• R0 rate

  at interval debulking surgery after 9 weeks

• The rate of chemotherapy response score 3

  9 weeks

Study Arms (1)

Neoadjuvant chemotherapy+Durvalumab+Tremelimumab

EXPERIMENTAL

1. Neoadjuvant treatment: Standard chemotherapy + Durvalumab + Tremelimumab Durvalumab : 1500mg q3 weeks (total 3 dosing) Tremelimumab : 75mg q 3 weeks (total 3 dosing) Chemotherapy regimen: Paclitaxel 175 mg/m2 , Carboplatin AUC 5-6 q3 weeks (total 3 dosing) 2. Interval debulking surgery 3. Adjuvant treatment: Standard chemotherapy + Durvalumab Durvalumab; 1120mg q3 weeks (total 12 dosing) Chemotherapy regimen: Paclitaxel 175mg/m2, carboplatin AUC 5-6 q 3weeks (total3 dosing)

Drug: Neoadjuvant chemotherapy+Durvalumab+Tremelimumab

Interventions

Neoadjuvant chemotherapy+Durvalumab+Tremelimumab DRUG

1. Neoadjuvant treatment: Standard chemotherapy + Durvalumab + Tremelimumab Durvalumab : 1500mg q3 weeks (total 3 dosing) Tremelimumab : 75mg q 3 weeks (total 3 dosing) Chemotherapy regimen: Paclitaxel 175 mg/m2 , Carboplatin AUC 5-6 q3 weeks (total 3 dosing) 2. Interval debulking surgery 3. Adjuvant treatment: Standard chemotherapy + Durvalumab Durvalumab; 1120mg q3 weeks (total 12 dosing) Chemotherapy regimen: Paclitaxel 175mg/m2, carboplatin AUC 5-6 q 3weeks (total3 dosing)

Neoadjuvant chemotherapy+Durvalumab+Tremelimumab

Eligibility Criteria

• Age: 20 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed adenocarcinoma of ovary, fallopian tube, primary peritoneum
• Clinical stage IIIC/IV
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization (eg, Health Insurance Portability and Accountability Act in the US, European Union \[EU\] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
• Female aged 20 years older at the time of acquisition of informed consent
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 \~ 1
• Must have life expectancy of at least 16 weeks
• Body weight \>30kg
• Adequate normal organ and marrow function as defined below:
• Haemoglobin ≥9.0 g/dL
• Absolute neutrophil count (ANC) ≥1.5 x 109/L
• Platelet count ≥100 x 109/L
• Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). \<\<This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.\>\>
• AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5x ULN
• Measured creatinine clearance (CL) \>40 mL/min or Calculated creatinine clearance CL\>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:
• Males: Creatinine CL (mL/min) = Weight (kg) x (140 - Age) 72 x serum creatinine (mg/dL) Females: Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 72 x serum creatinine (mg/dL)

You may not qualify if:

• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
• Participation in another clinical study with an investigational product during the last 60 days
• Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
• Any previous treatment with anti-PD-1, PD-L1, CTLA-4 (including durvalumab and tremelimumab)
• 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 or tremelimumab may be included only after consultation with the Study Physician.
• Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable. \<\<amend as required based on any combination studies with other anticancer agents\>\>
• Major surgical procedure (except diagnostic laparoscopy) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
• History of allogenic organ transplantation.
• 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 \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia
• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
• Any chronic skin condition that does not require systemic therapy
• Patients without active disease in the last 5 years may be included but only after consultation with the study physician
• Patients with celiac disease controlled by diet alone

Sponsors & Collaborators

• Yonsei University: lead
• AstraZeneca: collaborator
• Samsung Genomic Institute: collaborator
• Seoul National University Hospital: collaborator
• Samsung Medical Center: collaborator
• Korean Gynecologic Oncology Group: collaborator
• National Cancer Center, Korea: collaborator

Study Sites (4)

National Cancer Center, Korea

Gyeonggi-do, South Korea

NOT YET RECRUITING

Samsung Medical Center

Seoul, South Korea

NOT YET RECRUITING

Seoul National University Hospital

Seoul, South Korea

RECRUITING

Yonsei University Health System, Severance Hospital

Seoul, South Korea

RECRUITING

Related Publications (2)

• Park J, Lee JB, Lim MC, Kim BG, Kim JW, Kim S, Choi CH, Kim HS, Park SY, Lee JY; KGOG investigators. Phase II study of durvalumab and tremelimumab with front-line neoadjuvant chemotherapy in patients with advanced-stage ovarian cancer: primary analysis in the original cohort of KGOG3046/TRU-D. J Immunother Cancer. 2023 Oct;11(10):e007444. doi: 10.1136/jitc-2023-007444.

  PMID: 37865397 DERIVED

• Lee JY, Kim JW, Lim MC, Kim S, Kim HS, Choi CH, Yi JY, Park SY, Kim BG; KGOG investigators. A phase II study of neoadjuvant chemotherapy plus durvalumab and tremelimumab in advanced-stage ovarian cancer: a Korean Gynecologic Oncology Group Study (KGOG 3046), TRU-D. J Gynecol Oncol. 2019 Nov;30(6):e112. doi: 10.3802/jgo.2019.30.e112.

  PMID: 31576697 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms

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

Central Study Contacts

Jung-Yun Lee, MD., Ph.D

CONTACT

82-2-2228-2230; jungyunlee@yuhs.ac

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: This study is single arm phase II study to evaluate efficacy and safety of durvalumab and tremelimumab and chemotherapy in treatment-naïve clinical stage IIIC/IV ovarian cancer.

Study Record Dates

• First Submitted: March 28, 2019
• First Posted: April 2, 2019
• Study Start: July 4, 2019
• Primary Completion: May 1, 2021
• Study Completion: May 1, 2021
• Last Updated: September 28, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

KR (4)