Pamiparib and Low Dose Temozolomide In Patients With Platinum Sensitive Biliary Tract Cancer

NCT04796454 | Withdrawn Phase 2 DMC

• 1 other identifier: EORTC-1912-GITCG
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The main objective of this trial is to evaluate the activity of pamiparib plus low dose TMZ as maintenance treatment in improving progression free survival (PFS) in patients with advanced BTC who have received first line platinum-based chemotherapy. The primary objective is to test with a one-sided type I error of 10% whether pamiparib plus low dose TMZ as maintenance treatment increases PFS according to RECIST (version 1.1) in the entire study population as compared to standard treatment with Cisplatin-Gemcitabine chemotherapy regimen (or Gemcitabine-Oxaliplatin if cisplatin is contra-indicated). This is an open label randomized controlled multi-center phase II trial. Patients must meet all the criteria to be eligible. Eligible patients will be centrally randomized between the two arms in a 1:1 ratio. Randomization will be stratified by the following factors:

• Tumour response CR/PR vs SD vs non-measurable/non-PD after previous platinum-based chemotherapy as confirmed by central review
• Tumour location (intrahepatic bile ducts vs. gallbladder vs. perihilar bile ducts and distal bile duct and /ampulla of Vater tumours). Patients will receive treatment until progression or for a maximum period of 2 years.

Conditions

Platinum-Sensitive Biliary Tract Cancer

Keywords

Pamiparib; Biliary Tract Cancer; Temozolomide

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  Progression-free survival according to RECIST v1.1 from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months

  36 months from randomization

Secondary Outcomes (6)

• Incidence of adverse events (safety and toxicity)

  25 months from randomization

• PFS as per central review

  36 months from randomization

• overall survival (OS)

  36 months from randomization

• Best overall response

  36 months from randomization

• Global Health Status/Quality of Life/physical functioning

  6 months from randomization

Study Arms (2)

CisGem/GemOx

ACTIVE COMPARATOR

Cisplatin/Gemcitabine (3-week cycle): * Cisplatin IV 25 mg/m² d1 and day8 * Gemcitabine 1000 mg/m² d1 and d8 This treatment regimen will be given until documented disease progression, unacceptable toxicity, or patient refusal, for a maximum of 2 years. In case of unacceptable toxicity the CisGem regimen can also be switched to a GemOx regimen (4-week cycle): * Oxaliplatin IV 100 mg/m² d1 and day15 * Gemcitabine 1000 mg/m² d1 and d15

Drug: Cisplatin; Drug: Gemcitabine; Drug: Oxaliplatin

PamTMZ

EXPERIMENTAL

Pamiparib + temozolomide (4-week cycle): Pamiparib 60 mg PO twice a day d1-d28 Temozolomide 60 mg PO daily d1-d7 This treatment regimen will be given until documented disease progression, unacceptable toxicity, or patient refusal, for a maximum of 2 years.

Drug: Pamiparib; Drug: Temozolomide

Interventions

Cisplatin DRUG

Cisplatin IV 25 mg/m² on d1 and d8 - always combined with Gemcitabine; maximum treatment 2 years

CisGem/GemOx

Gemcitabine DRUG

Gemcitabine IV 1000 mg/m² on d1 and d8 if in combination with Cisplatin; Gemcitabine IV 1000 mg/m² on d1 and d15 if in combination with Oxaliplatin; maximum treatment 2 years

CisGem/GemOx

Oxaliplatin DRUG

Oxaliplatin IV 100 mg/m² on d1 and d15 - always combined with Gemcitabine; maximum treatment 2 years

CisGem/GemOx

Pamiparib DRUG

Pamiparib 60 mg PO twice a day from d1 to day28 in a 4-week cycle - always combined with Temozolomide; until progression or maximum treatment 2 years

PamTMZ

Temozolomide DRUG

Temozolomide 60 mg PO once a day from d1 to d7 in a 4-week cycle - always combined with Pamiparib; until progression or maximum treatment 2 years

PamTMZ

Eligibility Criteria

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

You may qualify if:

• ECOG Performance status 0-1
• Histologically-proven diagnosis of biliary tract adenocarcinoma(BTC): intrahepatic-, perihilar or distal bile duct adenocarcinoma, gallbladder adenocarcinoma or ampulla of Vater adenocarcinoma, as per AJCC 8th Edition.
• Note: patients with 'cholangiocarcinoma not otherwise specified but not intrahepatic' can be enrolled;
• Locally advanced, recurrent or metastatic disease stage
• Prior treatment: One maximum prior line of systemic treatment: Platinum-based treatment (CisGem or GemOx in case of contraindication to cisplatin) duration up to 18 weeks (4-6 cycles) for locally advanced or metastatic disease
• Patients should have completed at least 80 % of the planned dose
• Patients should have received the last dose at the maximum 2 weeks before study registration
• Non-progressive, measurable or non-measurable disease after platinum-based treatment as assessed by CT scan/MRI (RECIST 1.1), for central review
• Non-measurable disease is allowed if non PD as per RECIST 1.1 as confirmed by central review, and no radiological nor clinical progression as assessed by the investigator. In the absence of measurable disease, progression is defined as a change in non-measurable disease comparable in magnitude to the increase that would be required to declare PD for measurable disease or appearance of new metastatic lesions (RECIST 1.1).
• Normal 12-lead ECG (patients with abnormal ECG will be eligible if changes are not considered clinically significant by the local investigator)
• Adequate organs and hematologic function:
• Hemoglobin ≥ 9 g/dL (prior transfusions are allowed if they have been done ≥ 3-4 days before testing the haemoglobin Hb)
• White blood cell (WBC) ≥ 3.0 x 109/L
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelet count ≥ 100 x 109/L

You may not qualify if:

• Patients with squamous, all mixed with non-adenocarcinoma types (eg with neuroendocrine, hepatocellular, squamous, adenosquamous and medullar carcinoma)
• Prior therapy for BTC with an IDH 1 or 2 inhibitor or any other monoclonal antibodies
• Subjects with pleural effusion, pericardial effusion, or ascites with symptoms uncontrolled by medication or who require current drainage procedures (once monthly or more frequently).
• Central nervous system metastases or leptomeningeal spread of disease.
• Patients who are currently participating and receiving study therapy or have participated in a study with an investigational agent and received study therapy or used an investigational device wit weeks prior to enrolment/randomization.
• Patients with a previously treated malignancy are eligible to participate if all treatment of that malignancy was completed at least 2 years before registration and the patient has no evidence of disease. Exceptions: patients with currently treated basal cell, squamous cell carcinoma of the skin, localized treated low Gleason score prostate carcinoma (ie, resected prostate cancer staged pT1-2 with Gleason Score ≤ 6 and postoperative PSA \< 0.5 ng/ml), or in-situ carcinoma of the cervix are eligible.
• Inability to swallow and/ or retain oral tablets
• Malabsorption syndrome or other condition that would interfere with enteral absorption
• Serious infection requiring oral or IV antibiotics within 7 days prior to registration
• Known contraindication to either cisplatin, oxaliplatin, gemcitabine
• Known contraindication to imaging tracer or any product of contrast media and CT/MRI contraindications
• Hypersensitivity to the active substance temozolomide or to any of the excipients listed in the SmPC.
• Hypersensitivity to dacarbazine (DTIC).
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
• Has known history or current evidence of HIV

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead

MeSH Terms

Conditions

Biliary Tract Neoplasms

Interventions

Cisplatin; Gemcitabine; Oxaliplatin; pamiparib; Temozolomide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals; Dacarbazine; Triazenes; Imidazoles; Azoles

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2021
• First Posted: March 12, 2021
• Study Start: May 1, 2022
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: June 1, 2022

Record last verified: 2022-05