A Phase II Study of Durvalumab and Tremelimumab in combination with Neoadjuvant Carboplatin and Paclitaxel in newly diagnosed women with advanced high grade Serous Ovarian, Fallopian Tube and Peritoneal Cancers iPRIME”.
- Conditions
- Fallopian tube cancerPeritoneal cancerOvarian cancerCancer - Ovarian and primary peritoneal
- Registration Number
- ACTRN12618000109202
- Lead Sponsor
- Australia New Zealand Gynaecological Oncology Group (ANZGOG)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Female
- Target Recruitment
- 75
1. Signed, written informed consent obtained from the patient prior to performing any protocol-related procedures, including screening evaluations
2. Age greater than or equal to 18 years at the time of screening
3. Has a life expectancy of at least 12 weeks
4. Histologically or cytologically confirmed high grade serous ovarian carcinoma
5. FIGO stage IIIC or IV disease:
- A diagnosis of stage IIIC requires evidence of macroscopic, extra-pelvic, peritoneal metastasis > 2 cm ± positive retroperitoneal lymph nodes. Includes extension to capsule of liver/spleen. based on either laparoscopic or radiological assessment
- Stage IV disease is defined as either IVA: pleural effusion with positive cytology, or IVB: hepatic and/or splenic parenchymal metastasis, metastasis to extraabdominal organs (including inguinal lymph nodes and lymph nodes outside of the abdominal cavity)
6. Agree to undergo a pre-treatment biopsy either radiologically (core-needle) or via laparoscopy. Fine needle aspirate (FNA) alone is not acceptable.
7. Measurable disease according to RECIST 1.1 criteria
8. Considered to be both medically fit to receive NACT, and a suitable surgical candidate for interval debulking surgery by both the study investigator and the treating gynaecologic oncologist
9. ECOG performance status 0-1
10. Adequate normal organ and marrow function as defined below:
- Haemoglobin greater than or equal to 90g/L
- Absolute neutrophil count (ANC) greater than or equal to 1.5 x 109/L
- Platelet count greater than or equal to 100 x 109/L
- Serum bilirubin less than or equal to 1.5 x institutional upper limit of normal (ULN). This will not apply to patients with confirmed Gilberts syndrome (persistent or recurrent hyperbilirubinaemia that is predominantly unconjugated in the absence of haemolysis or hepatic pathology, who will be allowed only in consultation with the CPI
- AST (SGOT)/ALT (SGPT) less than or equal to 2.5 x ULN unless liver metastases are present, in which case it must be less than or equal to 5 x ULN
- Measured creatinine clearance (CL) >40mL/min or Calculated creatinine clearance >40mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine clearance
- Evidence of post-menopausal status or negative urinary or serum pregnancy test for pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause.
11. Patient is willing and able to comply with the protocol for the duration of the study including undergoing biopsies, treatment, and scheduled visits and examination including follow up
12. Body weight >30 kg
1. Previous chemotherapy, radiotherapy or surgery for ovarian cancer
2. Prior exposure to immune-mediated therapy including, but not limited to, other anti-CTLA-4, anti PD 1, anti-PD-L1, or anti-PD-L2 antibodies, including therapeutic anticancer vaccines.
3. Prior omentectomy
4. Patients with disease that is considered inoperable and in the opinion of the treating gynaecological oncologist is unlikely to become operable post NACT
5. Participation in another clinical study with an investigational product during the last 6 months
6. 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
7. Any unresolved toxicity NCI CTCAE Grade greater than or equal to 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
- Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the CPI
8. Any other concurrent chemotherapy, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non–cancer-related conditions (e.g., hormone replacement therapy) is acceptable
9. Major surgical procedure within 28 days prior to randomisation. A diagnostic laparoscopy or laparotomy is acceptable provided a debulking has not been performed.
10. History of allogenic organ transplantation
11. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., ulcerative 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 CPI
- Patients with coeliac disease controlled by diet alone
12. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
13. History of another primary malignancy except for
- Malignancy treated with curative intent and with no known active disease greater than or equal to 5 years before the randomisation and of low potential risk for recurrence
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
- Adequately treated carcinoma in situ without evidence of disease
14. History of leptomeningeal carcinomatosis
15. Brain metastases or spinal cord compression. Patients with suspected brain metastases at screening should have an MRI (preferred) or CT each preferably with IV contrast of the brain prior to randomisation
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method The proportion of participants who achieved a complete pathological response (CRS 3) after 3 cycles of neo-adjuvant durvalumab and tremelimumab, as assessed by Clinical Response Score, in patients who underwent interval debulking surgery (composite primary outcome).[ 9 weeks after treatment commencement and post surgery.]
- Secondary Outcome Measures
Name Time Method Progression free survival, defined as the time from randomisation to first documented disease progression by RECIST 1.1 or death from any cause, [ 12 months after treatment commencement.];The safety of neoadjuvant durvalumab and tremelimumab treatment, determined according to CTCAE 4.03 criteria.[ Week 3, 6, 9, 12, 15, 18, then 4-weekly thereafter, until 30 days after the last dose of treatment. ];The proportion of interval debulking surgery performed, assessed in terms of surgery completion rates.[ Between week 10 and 11 after treatment commencement.];To describe Heath-Related Quality of Life (HRQoL) in patients treated with Du-T-NACT, and compare with NACT alone, as assessed from the Functional Assessment of Cancer Therapy for Ovarian Cancer (FACT-O) questionnaire.[ Baseline, Cycles 1 through to 6 during the neo-adjuvant phase, then weeks 9, 21 and 33 during maintenance/observation phase.]