Phase I/II study of Nivolumab plus Lenvatinib for advanced biliary tract cancer

Phase 1

Completed

• Conditions: nresectable or recurrent biliary tract cancer

• Registration Number: JPRN-jRCT2091220436
• Lead Sponsor: ational Cancer Center Hospital

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-08-10
• Last Update Posted: 17 October 2023

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 53

Inclusion Criteria

1) Histologically proven adenocarcinoma
2) Unresectable or recurrent biliary tract cancer
3) [Phase I/II parts] after 1st line chemotherapy including Gemcitabine except surgery and biliary drainage for biliary tract cancer, and refractory to treatment, [Expansion cohort] no previous treatment except surgery and biliary drainage for biliary tract cancer
4) Recurrence more than 24 weeks (168 days) after ending of adjuvant S-1
5) age >=20 years
6) Performance status (Eastern Cooperative Oncology Group) of 0 or 1
7) adequate oral intake
8) More than one measurable region is required within 21 days before registration
9) no evidence of symptomatic brain metastasis, peritonitis carcinomatosis, nor spinal metastasis requiring radiotherapy
10) no evidence of pericardial fluid, pleural effusion or peritoneal effusion
11) Adequately controlled blood pressure irrespective usage of antihypertensive agent
12) No previous treatment of Lenvatinib, anti-PD-L1 antibody (Nivolumab, Pembrolizumab, etc.) anti-PD-1 antibody (Atezolizumab, Avelumab, Durvalumab, etc.), anti-CTLA-4 antibody (Ipilimumab etc.), and other agents controlling T-cell function.
13) No use of anticoagulant agent and antiplatelet agent.
14) No prior treatment (anticancer agent, radiotherapy including gamma knife, cyber knife, immunotherapy, anticancer vaccine) within 21 days before registration, except palliative radiotherapy for bone metastasis
15) No surgery under general anesthesia within 28 days before registration
16) Fulfilling all of (1)-(9) within 14 days before registration
(1) Neutrophil count >= 1,500 /mm3
(2) Platelets >= 100,000 /mm3
(3) Hemoglobin >= 8.5 g/dL
(4) AST <= 100 U/L ( or <= 150 U/L under biliary drainage)
(5) ALT <= 100 U/L ( or <= 150 U/L under biliary drainage)
(6) Serum total bilirubin <= 2.0 mg/dL
(7) Serum creatinine <= 1.2 mg/dL
(8) PT-INR <= 1.5
(9) Fulfill (i) or (ii)
(i) Negative or -1 urinary protein
(ii) if more than +1 urinary protein, 24-hour urinary protein excretion <=1g
17) Given consent to contraception
18) Written informed consent

Exclusion Criteria

1) Synchronous or metachronous (within 2 years) malignancies except carcinoma in situ or intramucosal tumor curatively treated with local therapy
2) Active infection requiring systemic therapy
3) Active hemoptysis (more than half a teaspoon of blood) within 21days before registration
4) Interstitial pneumonia and/or pulmonary fibrosis diagnosed by chest CT imaging or clinical examinations
5) Either HIV antibody, HTLV-1 antibody, HBs antigen, or HCV antibody is positive (except for HCV-RNA-negative even if HCV antibody-positive)
6) In case of Hbs antigen negative, HBs antibody or HBc antibody is positive, and HBV-DNA quantitative test positive
7) Pregnant or breast-feeding women, or women suspected of being pregnant
8) Psychiatric diseases or psychological symptoms interfering with participation in the trial
9) Taking Steroid equivalent more than 10 mg/day of prednisolone or systemic immunosuppressant (oral or intravenous) except temporary use for examination or prevention
10) History or complication due to hypersensitivity of antibody drug
11) Severe complication (cardiac insufficiency, renal insufficiency, liver insufficiency,
hemorrhagic peptic ulcer, paresis of intestine, ileus, uncontrolled diabetes mellitus, unhealed wound, or bone fracture)
12) Unstable angina pectoris within 3 weeks before registration, or myocardial infarction within 6 months before registration,
13) Grade >=2 adverse reactions caused by prior therapy except any grade of alopecia and Grade 2 of hypersensitivity and skin hyperpigmentation
14) Intestinal malabsorption, post total gastrectomy, or disease affecting absorption of Lenvatinib
15) Uncontrolled thyroid function with medication
16) long QTc interval (Fridericia's formula) more than 480 ms
17) Hemorrhagic disease or Thrombotic disease
18) Taking agent with strong cytochrome P450 (CYP)3A4 inhibition or induction
19) Active autoimmune disease except (1)-(4)
(1) vitiligo vulgaris, controlled type I diabetes mellitus, improved childhood asthma, and improved atopic dermatitis
(2) Current normal thyroid function with suspect of autoimmune thyroid dysfunction
(3) dysthyroidism able to maintain normal thyroid function only with hormonal therapy
(4) Psoriasis not requiring systemic therapy

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Phase I part: Proportion of adverse events corresponding toxicity evaluation criteria, Phase II part and Expansion cohort: Overall response by central imaging review

Secondary Outcome Measures

Name	Time	Method
Phase II part and Expansion cohort: Overall response by investigator's review, Progression-free survival, Overall survival, Disease control rate, Incidence of adverse events, and Incidence of severe adverse events