Study of TH-302 Monotherapy as Second-line Treatment in Advanced Biliary Tract Cancer

NCT02433639 | Completed Phase 2

• 1 other identifier: H-1412-023-631
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Biliary tract cancer is relatively rare cancer, with generally poor prognosis. In metastatic/recurrent biliary tract cancer, the most commonly used 1st-line chemotherapy is gemcitabine+cisplatin combination. However, there is no standard 2nd-line chemotherapy and there is no validated targeted therapeutic agent, even though this tumor harbors diverse genetic characteristics. TH-302 (1-methyl-2-nitro-1H-imidazole-5-yl)methyl N,N'-bis(2-bromoethyl) diamidophos-phate is a nitroimidazole-linked prodrug of a brominated version of isophosphoramide mustard (Br-IPM). When exposed to hypoxic conditions, TH-302 is reduced at the nitroimadazole site of the prodrug by intracellular reductases leading to the release of Br-IPM. Br-IPM can then act as a DNA crosslinking agent. In areas of normoxia, TH-302 remains intact as a prodrug and toxicity is minimized. In addition, preclinical data suggest that after activation, the active moiety may diffuse to areas outside the hypoxic region, demonstrating a "bystander" effect and possibly exhibiting additional anti-tumor activity. It is well known that biliary tract cancer is hypovascular tumor, so it contains large hypoxic area in the tumor. Therefore it would be worthy to test TH-302 in biliary tract cancer. This study is a phase II study of TH-302 monotherapy as second-line treatment in advanced biliary tract cancer, to investigate efficacy and safety of TH-302 monotherapy.

Conditions

Biliary Tract Cancer

Keywords

advanced biliary tract cancer, TH-302

Outcome Measures

Primary Outcomes (1)

• progression-free survival at 4-months (PFS4mo)

  PFS is defined as the interval from the date of enrollment to the date of disease progression or death due to any cause, whichever occurs first. PFS4m is defined as the proportion of patients alive and progression-free at 4 months relative to all enrolled patients.

  4 months

Secondary Outcomes (7)

• Objective Response Rate (ORR)

  6 months

• Disease Control Rate (DCR)

  6 months

• Duration of Response (DR)

  2 years

• Progression-Free Survival (PFS)

  2 years

• Time to Progression (TTP)

  10 months

Other Outcomes (1)

• protein/genomic biomarkers of efficacy from serum, plasma or tumor

  2 years

Study Arms (1)

treatment

EXPERIMENTAL

single arm study: TH-302 monotherapy is given

Drug: TH-302 monotherapy

Interventions

TH-302 monotherapy DRUG

TH-302 (480 ) mg/m2 D1, D8, D15 Q 4 weeks

treatment

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically / cytologically verified, non-resectable, recurrent, or metastatic biliary tract carcinoma including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma and gallbladder carcinoma.
• Patients who were previously treated with one palliative chemotherapy (patients who recurred within 6 months after completion or during adjuvant chemotherapy are allowed)
• Patients must have measurable or evaluable disease by RECIST 1.1
• ECOG PS: 0, 1
• Age ≥ 20 years
• Adequate bone marrow function defined as: Hb ≥ 8 g/dl, ANC ≥ 1500/mcL, Platelets ≥ 100K/mcL
• Adequate renal function defined as serum creatinine \< 1.6 mg/dl and/or measured creatinine clearance from 24-hour urine collection of ≥ 60 ml/min
• Adequate hepatic function defined as total bilirubin ≤ 2 mg/dl, ALT/AST ≤ 5 x ULN.
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Evidence of another active cancer that may influence patient outcome, except for nonmelanoma skin carcinoma, melanoma in-situ, in-situ carcinoma of the cervix curatively treated, treated superficial bladder cancer, and adenocarcinoma of the prostate that has been surgically treated with a post-treatment PSA that is non-detectable.
• Known brain metastases or primary central nervous system tumors with seizures that are not well controlled with standard medical therapy.
• Uncontrolled intercurrent illness including, but not limited to psychiatric illness/social situations that would limit compliance with study requirements.
• Known HIV positive patient
• Significant cardiovascular disease including congestive heart failure (New York Heart Association Class II or higher) or active angina pectoris.
• History of a myocardial infarction within 6 months.
• History of a stroke or transient ischemic attack within 6 months.
• Clinically significant peripheral vascular disease.
• Major surgical procedure within 4 weeks.
• Uncontrolled infection.
• Pregnant (positive pregnancy test)
• Breast-feeding should be discontinued if a nursing mother is to be treated on clinical trial.
• History of any organ or bone marrow transplant.
• Subjects who are taking medications that prolong QT interval and have a risk of Torsades de Pointes.
• Subjects taking a medication that is a moderate or strong inhibitor or inducer of CYP3A4.

Sponsors & Collaborators

• Seoul National University Hospital: lead
• Threshold Pharmaceuticals: collaborator

Study Sites (1)

Seoul National University Hospital

Seoul, 110-744, South Korea

Location

MeSH Terms

Conditions

Biliary Tract Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases

Study Officials

• Do-Youn Oh, MD, PhD

  Seoul National University Hospital

  PRINCIPAL INVESTIGATOR

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: Associate Professor

Study Record Dates

• First Submitted: April 26, 2015
• First Posted: May 5, 2015
• Study Start: April 1, 2015
• Primary Completion: October 1, 2017
• Study Completion: October 1, 2017
• Last Updated: September 10, 2018

Record last verified: 2018-09

Locations

KR (1)