Trial Title:
A Study of CDX-1140, a CD40 Agonist, in Combination With Capecitabine and Oxaliplatin (CAPOX) and Keytruda in Subjects With Biliary Tract Carcinoma (BTC)
NCT ID:
NCT05849480
Condition:
Biliary Cancer
Bile Duct Cancer
Cancer of the Bile Duct
Conditions: Official terms:
Bile Duct Neoplasms
Cholangiocarcinoma
Capecitabine
Oxaliplatin
Pembrolizumab
Conditions: Keywords:
Immunotherapy
Pembrolizumab
CAPOX
CDX-1140
CD40 agonist
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
oxaliplatin
Description:
Oxaliplatin (130 mg/m2) will be administered IV on Day 1 of each cycle, every 21 days (up
to 6 cycles).
Arm group label:
Phase I
Arm group label:
Phase II
Intervention type:
Drug
Intervention name:
capecitabine
Description:
Capecitabine (750 mg/m2 every 12 hours) will be administered orally with an intermittent
schedule: 2 weeks on, 1 week off, of each cycle, every 21 days (up to 6 cycles).
Arm group label:
Phase I
Arm group label:
Phase II
Intervention type:
Biological
Intervention name:
Keytruda
Description:
Pembrolizumab (200 mg) will be given IV on Day 8 of each cycle every 21 days (up to 6
cycles).
Arm group label:
Phase I
Arm group label:
Phase II
Intervention type:
Biological
Intervention name:
CDX-1140
Description:
CDX-1140 (0.36-1.5 mg/kg; per assigned dose level) will be given IV on Day 8 of each
cycle every 21 days (up to 6 cycles).
Arm group label:
Phase I
Arm group label:
Phase II
Summary:
Background:
Biliary tract carcinoma (BTC) is cancer of the slender tubes that carry fluids in the
liver. People with advanced BTC have few treatment options, and their survival rates are
very low.
Objective:
To test a study drug (CDX-1140) combined 3 other drugs (capecitabine, oxaliplatin,
Keytruda) in people with BTC.
Eligibility:
Adults aged 18 years or older with BTC that progressed after treatment and is not
eligible for surgery or liver transplant.
Design:
Participants will be screened. They will have a physical exam. They will have blood tests
and tests of their heart function. They will have imaging scans. They may need to have a
biopsy: A small sample of tissue will be taken from their tumor using a small needle.
Three of the drugs are given through a tube attached to a needle inserted into a vein in
the arm (intravenous). The fourth drug is a pill taken by mouth with water.
Participants will be treated in 21-day cycles. They will receive intravenous treatments
on day 1 and day 8 of the first 6 cycles. After that, they will receive intravenous
treatments only on day 1 of each cycle.
Participants will take the pill twice a day only for the first 2 weeks of each cycle.
They will stop taking this drug after 6 cycles.
Imaging scans will be repeated every 9 weeks.
Participants may continue receiving the study treatment for up to 2 years. Follow-up
visits, including imaging scans, will continue for 3 more years. These images may be
taken at other locations and sent to the researchers.
Detailed description:
Background:
Advanced biliary tract carcinoma (BTC) has limited treatment options in the second line
setting and a dismal prognosis.
Capecitabine and oxaliplatin (CAPOX) in combination with Keytruda is a tolerable and
potentially effective treatment for patients with refractory advanced BTC.
Programmed cell death protein 1 (PD-1) is an inhibitory receptor that is expressed by all
Tcells during activation. It regulates T-cell effector functions during various
physiological responses, including acute and chronic infection, cancer and autoimmunity,
and immune
homeostasis. Keytruda is a programmed death receptor-1 (PD-1)-blocking antibody indicated
for the treatment of different cancers including patients with hepatocellular carcinoma.
CD40-mediated activation of macrophages and dendritic cells (DC)s in intrahepatic
cholangiocarcinoma (iCCA) significantly improves response to anti-PD-1 therapy in
preclinical studies. The efficacy of this regimen is enhanced by first-line chemotherapy,
supporting the potential antitumor efficacy of the combination of CD40 agonist antibody
(anti-CD40) with anti-PD-1 and chemotherapy.
Objectives:
Phase I: To estimate safe dose of CDX-1140 used in combination with CAPOX, and Keytruda
(R)
Phase II:
To evaluate the 6-month progression free survival (PFS) in participants with advanced BTC
treated with CDX-1140, CAPOX, and Keytruda (R).
To determine the overall response rate (ORR) defined as complete response (CR) + partial
response (PR) according to RECIST 1.1 in participants with advanced BTC.
Eligibility:
Histopathological confirmation of BTC or histopathological confirmation of carcinoma in
the setting of clinical and radiological characteristics which, together with the
pathology,are highly suggestive of a diagnosis of BTC
Age >=18 years
Evaluable or measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST)
1.1
Design:
Phase I/II, single-arm, non-randomized trial of Keytruda(R) and CDX-1140 in combination
with CAPOX in participants with BTC in the second-line setting.
Initially, 9-12 participants will be enrolled into a Phase I portion of the trial. If
safe, we will continue enrollment as planned into Phase II, if not, we will close the
protocol.
After estimation of CDX-1140 recommended phase II dose, the first 13 participants
enrolled at this dose level of CDX-1140 in Phase I and Phase II will be evaluated for
progression. If among these 13 participants, no more than 2 can be progression-free at
the 6-months evaluation, then no further participants will be enrolled as soon as this
can be determined.
Criteria for eligibility:
Criteria:
- INCLUSION CRITERIA:
1. Participants must have histopathological confirmation of BTC or
histopathological confirmation of carcinoma in the setting of clinical and
radiological characteristics which, together with the pathology, are highly
suggestive of a diagnosis of BTC.
2. The maximum tumor size of any individual tumor or metastasis must be <= 8 cm.
3. Participants should have progressed on standard of care first line systemic
treatment or refused standard treatment.
4. Participants must have a disease that is not amenable to potentially curative
resection or liver transplantation.
5. Participants must have evaluable or measurable disease per RECIST 1.1
6. ECOG performance status of 0 to 1
7. Participants must have adequate organ and marrow function as defined below:
Absolute neutrophil count
(ANC) >= 1,000/mcL
Platelets >= 100,000/mcL
Total bilirubin <= 2.5 x ULN
ALT and AST <= 5 x ULN.
Creatinine OR Measured or calculated creatinine clearance (CrCl) (estimated
glomerular filtration rate (eGFR) may also be used in place of CrCl)
<1.5x institution upper limit of normal OR
>= 45 mL/min/1.73 m2 for participant with creatinine levels
>= 1.5 X institutional ULN
8. Age >=18 years.
9. Participants must have recovered from any acute toxicity related to prior
therapy, including surgery. Toxicity should be <= grade 1. Note: participants
with thyroid dysfunction caused by prior therapy including the need for chronic
therapy are eligible.
10. Women of child-bearing potential (WOCBP) and men must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) at the
study entry, for the duration of study treatment and up to 4 months after the
last dose of the CDX 1140 or Keytruda (R) (women and men), 9 months (women), 6
months (men) after completion of CAPOX therapy whatever comes later
11. Breastfeeding participants must be willing to discontinue breastfeeding from
study treatment initiation through 4 months after study treatment
discontinuation.
12. HBV-infected participants must be on antivirals and have HBV DNA <100 IU/mL.
HCV-infected participants can be enrolled if HCV RNA level is undetectable.
13. Participants must be able to understand and willing to sign a written informed
consent document.
EXCLUSION CRITERIA:
1. Participants who have had standard-of-care anti-cancer therapy or therapy with
investigational agents (e.g., chemotherapy, endocrine therapy, targeted therapy,
biologic therapy, tumor embolization, monoclonal antibodies, or other investigation
agents) or large field radiotherapy within 4 weeks prior to treatment initiation.
2. Prior therapy with anti- CD40.
3. Receiving of live vaccines within 30 days prior to the treatment initiation.
Examples of live vaccines include, but are not limited to, the following: measles,
mumps, rubella, varicella/zoster, yellow fever, rabies, Bacillus Calmette-Guerin,
and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed
virus vaccines and are allowed; however, intranasal influenza vaccines (e.g.,
FluMist (R)) are live attenuated vaccines and are not allowed.
4. Major surgery within 4 weeks prior to treatment initiation.
5. Active central nervous system metastases and/or carcinomatous meningitis.
6. HIV-infected participants.
7. History of (non-infectious) pneumonitis or current pneumonitis.
8. History of allergic reactions attributed to compounds of similar chemical or
biologic composition to study drugs or other agents used in study, such as
nivolumab, dacetuzumab, APX005M, ADC-1013.
9. Prior invasive malignancies within the past 3 years prior to treatment initiation
(with the exception of non-melanoma skin cancers, non-invasive bladder cancer, or
localized prostate cancer for whom systemic therapy is not required).
10. Any medical condition that requires chronic systemic steroid therapy, or any other
form of immunosuppressive medication (inhaled and topical steroids are permitted).
11. History of chronic autoimmune disease (e.g., Addison s disease, multiple sclerosis,
Graves disease, Hashimoto s thyroiditis, rheumatoid arthritis, hypophysitis,
systemic lupus erythematosus, Wegener s granulomatosis, sarcoidosis syndrome, etc.)
or other connective tissue diseases with the symptomatic disease within the 3 years
of initiation of study treatment. Note: Active vitiligo or a history of vitiligo
will not be a basis for exclusion.
12. Fridericia's corrected QT interval (QTcF) >= 480 msec or other factors that increase
the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia,
family history of long QT interval syndrome.
13. Participants who were not able to tolerate prior immune checkpoint inhibitor
therapy.
14. Uncontrolled intercurrent illness or psychiatric illness/social situations that
would limit compliance with study requirements.
15. Pregnancy.
Gender:
All
Minimum age:
18 Years
Maximum age:
120 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
National Institutes of Health Clinical Center
Address:
City:
Bethesda
Zip:
20892
Country:
United States
Status:
Recruiting
Contact:
Last name:
National Cancer Institute Referral Office
Phone:
888-624-1937
Start date:
May 8, 2024
Completion date:
June 1, 2042
Lead sponsor:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
National Institutes of Health Clinical Center (CC)
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05849480
https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_001548-C.html
