Maintenance Niraparib and Dostarlimab in Advanced Cholangiocarcinoma

NCT04895046 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: HCRN GI19-414
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Phase II, single arm trial, evaluating molecularly selected, immune-based combination therapy in maintenance treatments for advanced cholangiocarcinoma, selecting patients on the homologous recombination deficient (HRD) signature.

Conditions

HRD; Cholangiocarcinoma; Metastatic Cancer

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  Evaluate PFS of patients who achieved a complete response (CR), partial response (PR) or stable disease (SD). PFS is defined as the date of treatment initiation (C1D1) until the criteria for disease progression is met as defined by RECIST 1.1 or death occurs

  4-6 months

Secondary Outcomes (5)

• Objective Response Rate (ORR)

  5 years

• Overall Survival (OS)

  5years

• Duration of Response (DOR)

  5 years

• Disease Control Rate (DCR)

  5 years

• Frequency and Severity of Adverse Events

  5 years

Study Arms (1)

Investigational Group

EXPERIMENTAL

Cycle 1-4 (cycle length 4 weeks): Niraparib 300 mg taken orally on days 1-21 and Dostarlimab 500 mg intravenously on day 1 Cycle 5 and above (cycle length 3 weeks): Niraparib 300 mg taken orally on days 1-21 and 1000 mg intravenously on day 1 of every other cycle

Drug: Niraparib; Drug: Dostarlimab

Interventions

Niraparib DRUG

300 mg taken orally (all cycles)

Also known as: Zejula

Investigational Group

Dostarlimab DRUG

500 mg (cycles 1-4) intravenously

Also known as: TSR-042, GSK4057190

Investigational Group

Eligibility Criteria

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

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status of 0-1 within 14 days prior to registration.
• Histological or cytological documentation of metastatic adenocarcinoma of the biliary tract per AJCC, 8th edition.
• Measurable disease according to RECIST 1.1 within 28 days prior to registration.
• Must have a defined HRD signature (BRCA1, BRCA2, PALB2, MRE, CHEK1, CHEK2, PTEN, ATM, ATR, BER, RPA1, RAD51, BARD1, BRIP1, FAAP20, FANCM, FAN1, NBN, EMSY, MRE11, ARID1A, BAP-1.) NOTE: Clinical Laboratory Improvement Act (CLIA)-certified assays including commercial tests (Foundation Medicine, Caris, Tempus, Guardant 360 or other platforms of next generation sequencing) will be allowed.
• Patients must have achieved complete response (CR), partial response (PR) or stable disease (SD) after 4 to 6 months of any platinum-based therapy.
• Prior treatment with immune therapy is allowed. Exception: prior treatment with PARP inhibitors is not allowed.
• Prior cancer treatment must be completed at least 21 days prior to registration. Toxicities attributed to prior therapy/procedure must have resolved to Grade ≤ 1. Exceptions include alopecia and oxaliplatin induced neurotoxicity ≤ Grade 2. C1D1 treatment will start no more than 28 days after completion of prior cancer treatment. Patients that are \> 28 days from completion of prior treatment will need to be discussed with the sponsor-investigator.
• Life expectancy of ≥ 16 weeks per estimation of site investigator.
• Demonstrate adequate organ function as defined in the table in the protocol. All screening labs to be obtained within 7 days prior to registration.
• Negative urine or serum pregnancy test done ≤ 72 hours prior to C1D1 for women of childbearing potential.
• Women of childbearing potential and their partners, who are sexually active, must agree to the use contraception as described in the protocol.
• Male patients must use contraception as described in the protocol.
• Participants with known Hepatitis B viral infection that is controlled on nucleos(t)ide analogs (eg entecavir or tenofovir) per investigator discretion and will be continued for the duration of the study are eligible. NOTE: Risk of HBV reactivation should be considered in all patients and the need for anti-HBV prophylaxis should be carefully assessed prior to the initiation of anticancer therapy. Testing is not required at screening. Status should be assessed through medical history and if there is a question testing may be done at the discretion of the investigator based on local guidelines. This testing would be considered standard of care.

You may not qualify if:

• Subjects meeting any of the criteria below may not participate in the study:
• Patient is simultaneously enrolled in any interventional clinical trial.
• Tumor embolization ≤ 4 weeks prior to registration.
• Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism ≤ 6 months prior to registration.
• Evidence or history of bleeding diathesis or any hemorrhage or bleeding event \> CTCAE v5.0 grade 3, ≤ 4 weeks prior to registration.
• Radiotherapy encompassing \> 20% of the bone marrow within 2 weeks prior to registration. Palliative radiation therapy to a small field \>1 week prior to Day 1 of study treatment may be allowed.
• Major surgical procedure, open biopsy, or significant traumatic injury ≤ 28 days prior to registration AND have recovered from surgery.
• Congestive heart failure - New York Heart Association (NYHA) ≥ Class II.
• Uncontrolled cardiac conditions (eg. unstable ischemia, uncontrolled symptomatic arrhythmia, cardiac arrhythmias requiring anti-arrhythmic therapy, corrected QT interval by Fridericia's correction formula (QTcF) prolongation \> 500 ms, or patients with congenital long QT syndrome. NOTE: Pacemaker, beta blockers or digoxin are permitted.
• Ongoing infection \> Grade 2 National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0.
• Patient taking medications with a known risk to prolong the QTc interval and/or cause Torsades de Pointes. NOTE: Patients must be discontinued ≥ 7 days of registration. Treating physicians may wish to replace the drug(s) that do not carry this risk with safe alternative(s).
• Uncontrolled hypertension. (Systolic blood pressure \> 140 mmHg or diastolic pressure \> 90 mmHg despite optimal medical management).
• Seizure disorder requiring medication.
• Participant has leptomeningeal disease, carcinomatous meningitis, symptomatic brain metastases, or radiologic signs of CNS hemorrhage. NOTE: Participants with asymptomatic brain metastases (i.e. off corticosteroids and anticonvulsants for at least 7 days) are permitted.
• Non-healing wound, ulcer, or bone fracture.

Sponsors & Collaborators

• Walid Shaib, MD: lead
• Emory University: collaborator
• GlaxoSmithKline: collaborator

MeSH Terms

Conditions

Cholangiocarcinoma; Neoplasm Metastasis

Interventions

niraparib; dostarlimab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Walid Shaib, MD

  Emory University

  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: SPONSOR INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: May 17, 2021
• First Posted: May 20, 2021
• Study Start: October 11, 2021
• Primary Completion: September 1, 2022
• Study Completion: September 1, 2023
• Last Updated: June 29, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share