A Phase II Study of Immunotherapy With Durvalumab and Tremelimumab in Combination With Capecitabine or Without Capecitabine in Adjuvant Situation for Biliary Tract Cancer
Overview
- Phase
- Phase 2
- Intervention
- Durvalumab
- Conditions
- Biliary Tract Cancer (CCA)
- Sponsor
- Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
- Enrollment
- 40
- Locations
- 1
- Primary Endpoint
- Recurrence free survival at 12 months (RFS@12).
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This is an interventional, prospective multicenter, open-label, phase II study in patients after curative surgery for BTC in a classic adjuvant situation, consisting of a two arm feasibility pilot part with a randomized pick-the-winner design and an option to proceed into a randomized phase 2/3 trial in order to compare the winner with the current SOC (capecitabine).
Detailed Description
The primary objective is to assess the anti-tumor activity of the combination of durvalumab and tremelimumab with or without capecitabine by the recurrence-free survival rate after 12 months (RFS@12). Secondary objectives are to assess the efficacy by recurrence-free surviaval (RFS) and overall survival (OS); to assess safety of the combination treatments (AEs, impact on liver function, use of subsequent therapies); to assess quality of life (QoL). Exploratory objective is to perform correlation analysis between selected molecular parameters and clinical data to identify molecular biomarkers predictive for RFS and OS. Patients will be stratified according to the tumor site (ICC vs. ECC vs. gallbladder) and resection status (R0 vs. R1). In this pilot trial phase, a pick the winner design is applied to determine wether treatment with durvalumab and tremelimumab in combination with or without capecitabine is more promising. In the initial pilot phase, 40 patients with histologically proven and curatively resected biliary tract cancer (intrahepatic, hilar or distal CCA as well gallbladder carcinoma) without metastatic disease, will be enrolled in a 1:1 randomized design (i.e. 20 patients per Arm). Patients will be recruited from up to 15 sites and patients withdrawn from the trial will not be replaced.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Capable of giving written informed consent, including participation in optional translational research if applicable, and any locally-required authorization (EU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations.
- •Histologically proven and curatively resected biliary tract cancer (intrahepatic, hilar or distal CCA as well gallbladder carcinoma) without metastatic disease, in the adjuvant situation (R0/R1) up to 16 weeks from surgery.
- •Men or women\* ≥ 18 years at time of study entry.
- •\*There is no data that indicates a specific gender distribution. Therefore, patients are included regardless of their gender.
- •Performance status (PS) ≤ 1 (ECOG scale),with no deterioration over the previous two weeks prior to baseline.
- •Must have a life expectancy of at least 12 weeks
- •Appropriate hematological, hepatic and renal function:
- •Absolute number of neutrophils (ANC) ≥ 1.5 x 109/L
- •Platelets ≥ 100 x 109/L
- •Hemoglobin ≥ 9 g/dL (5.58 mmol/L)
Exclusion Criteria
- •Presence of tumors other than biliary tract cancer or a secondary tumor other than squamous or basal cell carcinomas of the skin or in situ carcinomas of the cervix which have been effectively treated. Patients who have received curative treatment for other tumors and have been disease-free for at least 5 years at the time of screening are eligible for enrollment.
- •Metastatic biliary tract cancer disease.
- •Simultaneous, ongoing systemic immunotherapy, chemotherapy, or hormone therapy not described in the study protocol.
- •Simultaneous treatment with a different anti-cancer therapy other than that provided for in the study (excluding palliative radiotherapy only for symptom control)
- •Previous therapy with a PD-1, PD-L1 inhibitor (including durvalumab) or CTLA4 inhibitor (including tremelimumab) or classical chemotherapy agents like platinum, fluoropyrimidine or gemcitabine based regimens.
- •Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
- •Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the LKP.
- •Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the LKP.
- •Stage B cirrhosis according to Child-Pugh criteria (or worse) or cirrhosis (of any grade) with a history of hepatic encephalopathy or clinically significant ascites resulting from cirrhosis. Clinically significant ascites is defined as ascites resulting from cirrhosis requiring diuretics or paracentesis.
- •Known allergic / hypersensitive reactions to at least one of the treatment components.
Arms & Interventions
A: Cape+Durva+Treme
Capecitabine + Durvalumab + Tremelimumab
Intervention: Durvalumab
A: Cape+Durva+Treme
Capecitabine + Durvalumab + Tremelimumab
Intervention: Tremelimumab
A: Cape+Durva+Treme
Capecitabine + Durvalumab + Tremelimumab
Intervention: Capecitabine
B: Durva+Treme
Durvalumab + Tremelimumab
Intervention: Durvalumab
B: Durva+Treme
Durvalumab + Tremelimumab
Intervention: Tremelimumab
Outcomes
Primary Outcomes
Recurrence free survival at 12 months (RFS@12).
Time Frame: 12 months
Recurrence free survival at 12 months (RFS@12) will be defined as the proportion of allocated subjects without any recurrence/progression and alive at 12 months after the date of treatment allocation.
Secondary Outcomes
- Recurrence free survival (RFS)(30 months)
- Overall survival (OS)(30 months)
- Safety: (serious) adverse events(30 months)
- QoL BIL21(30 months)
- QoL QLQ-C30(30 months)
- QoL EQ-5D-5L(30 months)