ABC-08: Phase Ib Trial of Acelarin in Combination With Cisplatin in Locally Advanced/ Metastatic Biliary Tract Cancers

NCT02351765 | Completed Phase 1 DMC

• 2 other identifiers: CFTSp0962015-000100-26
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to determine the recommended phase II dose, and to assess the safety of acelarin in combination with cisplatin in patients with locally advanced/ metastatic biliary tract cancers.

Conditions

Biliary Tract Cancer; Gallbladder Cancer; Cholangiocarcinoma; Ampullary Cancer

Outcome Measures

Primary Outcomes (2)

• Safety profile of Acelarin in combination with Cisplatin, assessed by total incidence and rate of grade 3 and 4 adverse events according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)

  Safety will be assessed by comparing the total incidence and rate of grade 3 and 4 adverse events that occur after initiation of therapy, according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)

  Adverse events recorded from initiation of therapy until 30 day post-treatment

• Maximum Tolerated Dose (MTD) of Aclerain in combination with Cisplatin

  The MTD will be defined as the maximum dose level at which 0/3 patients or 1/6 patients experience dose-limiting toxicity (DLT). At any dose level, DLT in 1/3 patients will lead to expansion to 6 patients. If 2/6 patients experience DLT the preceding dose level will be declared the MTD. At the MTD up to 6 additional patients may be enrolled. If this level is well tolerated, it will be declared the recommended phase II dose (RP2D).

  After 13 months of first patient included

Secondary Outcomes (4)

• Progression-free survival

  Evaluated by 6 weekly follow-up until 12 months after the last patient included

• Overall survival

  Evaluated by 6 weekly follow-up until 12 months after the last patient included

• Response rate

  After 12 weeks of treatment

• Exploration of the pharmacokinetic profile for the combination of Acelarin with Cisplatin

  At baseline (prior to chemotherapy administration), 30, 60 and 240 minutes following line flush at the end of acelarin administration. Cycle 1 day 1 only

Study Arms (1)

Acelarin & Cisplatin

EXPERIMENTAL

The maximum tolerated dose (MTD) of Acelarin in combination with 25mg/m2 Cisplatin will be determined. The starting dose will be 625mg/m2 Acelarin which will be escalated to 725mg/m2 if the criteria for dose escalation is met (i.e. the proportion of dose limiting toxicities is acceptable as detailed in the protocol). Escalation will continue in accordance with the protocol up to a maximum of 925mg/m2. Only if the MTD is exceeded at the starting dose level (at least 2 of 3 participants or at least 2 of 6 participants have DLT at the first dose level) will there be a de-escalation to 500mg.

Drug: Acelarin; Drug: Cisplatin

Interventions

Acelarin DRUG

First-in-class nucleotide analogue

Also known as: Code name: NUC-1031

Acelarin & Cisplatin

Cisplatin DRUG

Platinum-compound chemotherapy drug

Also known as: Anatomical Therapeutic Chemical (ATC) code: L01XA01

Acelarin & Cisplatin

Eligibility Criteria

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

You may qualify if:

• Histologically/cytologically verified, non-resectable or recurrent/metastatic cholangiocarcinoma, gallbladder or ampullary carcinoma.
• No prior systemic therapy allowed for advanced biliary cancer. Prior low dose chemotherapy used with or without radiotherapy in the adjuvant setting is allowed if completed \> 6 months from enrolment. Recent palliative radiation (within 28 days prior to consent) is allowed if candidate has measurable disease outside radiation field.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Age ≥ 18 years and life expectancy \> 3 months.
• Adequate renal function with serum urea and serum creatinine \< 1.5 times upper limit of normal (ULN) and creatinine clearance ≥ 30ml/min.
• Adequate haematological function: Hb ≥ 10g/dl, white blood count (WBC) ≥ 3.0 x 10\*9/L, absolute neutrophil count (ANC) ≥ 1.5 x 10\*9/L, platelet count ≥ 100,000/mm3.
• Adequate liver function: total bilirubin \< 30 μmol/L and alkaline phosphatase, along with aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤ 5 x ULN.
• Adequate biliary drainage, with no evidence of ongoing infection.
• Women of child bearing age MUST have a negative pregnancy test prior to study entry AND be using a highly effective contraception method (combined or progestogen-only hormonal contraception, intrauterine device, intrauterine hormone-releasing system, vasectomised partner\*(a) or sexual abstinence\*\*(b)) which must be continued for 6 months after the end of study treatment, unless child bearing potential has been terminated by surgery/radical radiotherapy or infertility due to bilateral tubal occlusion.
• Male subjects must either have had a successful vasectomy (confirmed azoospermia) or they and their female partner meet the criteria above (not of childbearing potential or practicing adequate contraception \[e.g. combined or progestogen-only hormonal contraception, intrauterine device, intrauterine hormone-releasing system, sexual abstinence\*\*(b)\] throughout the study period and for 6 months after the end of study treatment).
• Patients must not have a history of other malignant diseases (within the previous 5 years and there must be no evidence of recurrence), other than adequately treated non-melanotic skin cancer or in-situ carcinoma of the uterine cervix.
• Patients must have given written informed consent.
• (a) The vasectomised partner must have received medical assessment confirming surgical success.
• (b) Sexual abstinence in line with the preferred and usual lifestyle of the subject.

You may not qualify if:

• History of allergic reactions attributed to previous gemcitabine or cisplatin treatment.
• Documented history of allergic reactions attributed to any of the excipients used in the formulation (Kolliphor ELP; Tween 80; DMA).
• Previous treatment with Acelarin.
• Incomplete recovery from previous therapy (surgery/adjuvant therapy/radiotherapy) or unresolved biliary tree obstruction.
• Any evidence of severe or uncontrolled systemic diseases which, in the view of the investigator, makes it undesirable for the patient to participate in the trial.
• Evidence of significant clinical disorder or laboratory finding which, in the opinion of the investigator makes it undesirable for the patient to participate in the trial.
• Any patient with a medical or psychiatric condition that impairs their ability to give informed consent.
• Any other serious uncontrolled medical conditions.
• Clinical evidence of metastatic disease to the brain.
• Any pregnant or lactating woman.
• Pre-existing hearing impairment.

Sponsors & Collaborators

• The Christie NHS Foundation Trust: lead

Study Sites (5)

Beatson Oncology Centre

Glasgow, United Kingdom

Location

Clatterbridge Cancer Centre

Liverpool, United Kingdom

Location

Imperial College London

London, United Kingdom

Location

University College London

London, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, United Kingdom

Location

Related Publications (1)

• McNamara MG, Bridgewater J, Palmer DH, Faluyi O, Wasan H, Patel A, Ryder WD, Barber S, Gnanaranjan C, Ghazaly E, Evans TRJ, Valle JW. A Phase Ib Study of NUC-1031 in Combination with Cisplatin for the First-Line Treatment of Patients with Advanced Biliary Tract Cancer (ABC-08). Oncologist. 2021 Apr;26(4):e669-e678. doi: 10.1002/onco.13598. Epub 2020 Dec 3.

  PMID: 33210382 DERIVED

MeSH Terms

Conditions

Biliary Tract Neoplasms; Gallbladder Neoplasms; Cholangiocarcinoma

Interventions

NUC-1031; Cisplatin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Mairéad G McNamara, MD

  The Christie NHS Foundation Trust

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2015
• First Posted: January 30, 2015
• Study Start: January 1, 2016
• Primary Completion: March 1, 2019
• Study Completion: March 1, 2019
• Last Updated: May 17, 2023

Record last verified: 2023-05

Locations

GB (5)