Cabozantinib (XL-184) Monotherapy for Advanced Cholangiocarcinoma

NCT01954745 | Completed Phase 2 Results DMC

• 2 other identifiers: 13-221XL184-IST26
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 3

Brief Summary

This research study is evaluating a drug called cabozantinib as a possible treatment cancer of the bile duct. Cabozantinib is a drug that targets specific pathways inside the cells of the body. By blocking the c-MET and VEGFR2 pathways from sending signals, cabozantinib may prevent cells from multiplying. This drug has been used in other research studies and information from those other research studies suggests that this drug may help to stop the growth of bile duct cancer. In this research study, the investigators are looking to see how well cabozantinib works in slowing the growth of bile duct cancer. The investigators are also assessing the safety and tolerability of cabozantinib in participants with this type of cancer.

Conditions

Bile Duct Cancer; Intrahepatic Cholangiocarcinoma; Cholangiocarcinoma of the Extrahepatic Bile Duct

Keywords

Bile Duct Cancer; intrahepatic cholangiocarcinoma; extrahepatic cholangiocarcinoma; Cabozantinib

Outcome Measures

Primary Outcomes (1)

• Median Progression Free Survival (PFS)

  To evaluate the median progression free survival (PFS) of cabozantinib in patients with advanced cholangiocarcinoma after progression on 1 or 2 prior systemic therapies.

  2 Years

Secondary Outcomes (3)

• Number of Patients With Adverse Events

  2 Years

• Objective Response Rate (ORR)

  2 Years

• Median Overall Survival (OS)

  2 years

Study Arms (1)

Cabozantinib

EXPERIMENTAL

Patients will be treated with cabozantinib 60 mg daily administered orally continuously for 28-day cycles. Tumor assessments will be performed every 8 weeks until documented disease progression by RECIST criteria or drug intolerance.

Drug: Cabozantinib

Interventions

Cabozantinib DRUG

Cabozantinib 60 mg (free base weight) per day will be administered daily and continuously for a cycle length of 28 days. Subjects will be provided with a sufficient supply of study treatment and instructions for taking the study treatment on days without scheduled clinic visits. After fasting (with exception of water) for 2 hours, subjects will take study treatment daily with a full glass of water (minimum of 8 oz/ 240 mL) and continue to fast for 1 hour after each dose of study treatment.

Also known as: XL-184

Cabozantinib

Eligibility Criteria

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

You may qualify if:

• Participants must have unresectable or metastatic histologically or cytologically confirmed intrahepatic cholangiocarcinoma or extrahepatic cholangiocarcinoma (i.e. hilar and distal cholangiocarcinoma).
• Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \> 20 mm with conventional techniques or as \> 10 mm with spiral CT scan. See section 10 for the evaluation of measureable disease.
• Participants must have failed at least 1 but no more than 2 lines of systemic regimens for advanced cholangiocarcinoma due to disease progression or toxicity.
• Age ≥ 18 years.
• Life expectancy of ≥ 3 months.
• ECOG performance status \< 1 (see Appendix A).
• Participants must have adequate organ and marrow function as defined below:
• Absolute neutrophil count \> 1,500/mcL
• Platelets \> 100,000/mcL
• Hemoglobin ≥ 9 g/dL
• Total bilirubin ≤ 2.0 x the upper limit of normal
• AST (SGOT)/ALT (SGPT) ≤ 5 X institutional upper limit of normal
• PT/PTT ≤ 1.5 x ULN
• Creatinine ≤ 1.5 or GFR ≥ 60 mL/min/1.73m2
• Lipase \< 2.0 x the upper limit of normal and no radiologic or clinical evidence of pancreatitis

You may not qualify if:

• Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study.
• Prior treatment with cabozantinib or other VEGF-R directed therapies
• Gallbladder carcinoma or periampullary tumors
• Chemotherapy within 4 weeks prior to entering the study (6 weeks for nitrosoureas or mitomycin) or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
• The subject has received radiation therapy:
• to the thoracic cavity, abdomen or pelvis within 3 months of the first dose of study treatment or has with ongoing complications or is without complete recovery and healing from prior radiation therapy
• to bone or brain metastasis within 14 days of the first dose of study treatment
• to any other site(s) within 28 days of the first dose of study treatment
• The subject has a primary brain tumor.
• The subject has active brain metastases or epidural disease (Note: Subjects with brain metastases previously treated with whole brain radiation or radiosurgery or subjects with epidural disease previously treated with radiation or surgery who are asymptomatic and do not require steroid treatment for at least 2 weeks before starting study treatment are eligible. Neurosurgical resection of brain metastases or brain biopsy is permitted if completed at least 3 months before starting study treatment. (Baseline brain imaging with contrast-enhanced CT or MRI scans for subjects with known brain metastases is required to confirm eligibility.)
• The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• Cardiovascular disorders including
• Congestive heart failure (CHF): New York Heart Association (NYHA) Class III (moderate) or Class IV (severe) at the time of screening
• Concurrent uncontrolled hypertension defined as sustained BP \> 140 mm Hg systolic, or \> 90 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment
• Any history of congenital long QT syndrome

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Exelixis: collaborator

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02215, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• Goyal L, Zheng H, Yurgelun MB, Abrams TA, Allen JN, Cleary JM, Knowles M, Regan E, Reardon A, Khachatryan A, Jain RK, Nardi V, Borger DR, Duda DG, Zhu AX. A phase 2 and biomarker study of cabozantinib in patients with advanced cholangiocarcinoma. Cancer. 2017 Jun 1;123(11):1979-1988. doi: 10.1002/cncr.30571. Epub 2017 Feb 13.

  PMID: 28192597 DERIVED

MeSH Terms

Conditions

Bile Duct Neoplasms; Cholangiocarcinoma

Interventions

cabozantinib

Condition Hierarchy (Ancestors)

Biliary Tract Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Limitations and Caveats

After 12 patients failed to be progression-free at 16 weeks, the study was terminated as it was determined that the criterion for proceeding to stage 2 could not be met. (i.e. 9 of 20 patients needed to be progression free at 4 months.)

Results Point of Contact

• Title: Dr. Lipika Goyal
• Organization: Massachusetts General Hospital Cancer Center

Lgoyal@partners.org

617-724-4000

Study Officials

• Lipika Goyal, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 24, 2013
• First Posted: October 7, 2013
• Study Start: September 1, 2013
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2016
• Last Updated: February 3, 2017
• Results First Posted: February 3, 2017

Record last verified: 2016-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)