Study of Olaparib and Durvalumab in IDH-Mutated Solid Tumors

NCT03991832 | Recruiting Phase 2 DMC

• 2 other identifiers: 19-5526SOLID
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 2 study of the combination of drugs olaparib and durvalumab for the treatment of isocitrate dehydrogenase or (IDH) mutated solid tumors. The purpose of this study is to assess the efficacy of the drug combination via overall response rate and overall disease control rate. It is believed that giving olaparib and durvalumab together would be more useful when given to patients with IDH-mutated solid tumors than giving each drug alone.

Conditions

Glioma; Cholangiocarcinoma; Solid Tumor; IDH Mutation

Outcome Measures

Primary Outcomes (2)

• Overall response rate

  overall + partial response

  3 years

• Overall disease control rate

  for both cohorts

  3 years

Secondary Outcomes (3)

• Progression-free survival

  3 years

• Overall survival

  3 years

• Number of incidences of adverse events

  3 years

Study Arms (2)

Cohort A: IDH mutated glioma

EXPERIMENTAL

Olaparib, by mouth (orally), twice a day, every day. Durvalumab, by vein (intravenously), on Day 1 of every 28 day cycle.

Drug: Olaparib; Drug: Durvalumab

Cohort B: IDH mutated cholangiocarcinoma

EXPERIMENTAL

Olaparib, by mouth (orally), twice a day, every day. Durvalumab, by vein (intravenously), on Day 1 of every 28 day cycle.

Drug: Olaparib; Drug: Durvalumab

Interventions

Olaparib DRUG

Olaparib is a drug that blocks a protein called poly (ADP-ribose) polymerase (PARP). PARP is important in the growth and spread of cancer cells. Because of this, blocking PARP from working is expected to stop the growth of or shrink cancer cells.

Also known as: Lynparza

Cohort A: IDH mutated glioma; Cohort B: IDH mutated cholangiocarcinoma

Durvalumab DRUG

Durvalumab is a drug that works by stopping a protein called Programmed Cell Death Ligand 1 (PD-L1) from working. PD-L1 is a protein that is thought to prevent the immune system (the body's defense against diseases) from killing cancer cells. Stopping PD-L1 from working is expected to allow the immune system to once again prevent or slow down cancer growth.

Also known as: Imfinzi

Cohort A: IDH mutated glioma; Cohort B: IDH mutated cholangiocarcinoma

Eligibility Criteria

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

You may qualify if:

• Provision of informed consent prior to any study specific procedures.
• Must be ≥ 18 years.
• Body weight \> 30 kg.
• For Cohort A: Patients must have histologically or cytologically confirmed diffuse astrocytic and oligodendroglial tumors by World Health Organization 2016 classification which are IDH mutant. They must have not received more than 2 regimens of systemic therapy after initial relapse.
• For Cohort B: Patients must have histologically or cytologically confirmed adenocarcinoma of the biliary tract which are IDH mutant. They must have not received more than 2 regimens of systemic therapy for advanced disease.
• Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Patients must have a life expectancy ≥ 16 weeks.
• All participants must agree to use methods to prevent pregnancy as agreed upon between the participant and the study doctor from the signing of the informed consent form and continue throughout the period of taking study treatments and for 3 months after the last doses of study drugs.
• Patients are willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
• Patients in Cohorts A and B must have measurable disease
• Patients with glioma or central nervous system (CNS) metastases must be asymptomatic and at least 28 days after the most recent CNS treatment and is clinically stable, and at least 14 days on stable doses of corticosteroids and/or anti-seizure medications.

You may not qualify if:

• Involvement in the planning and/or conduct of the study.
• Concurrent enrolment in another clinical study, unless it is an observational (non-intervention) clinical study or the follow-up period of an interventional study.
• Receipt of any conventional or investigational anticancer therapy within 4 weeks prior to the planned first dose of olaparib and durvalumab.
• Any previous treatment with PARP inhibitor or PD-1/PD-L1 inhibitors including olaparib and durvalumab.
• Other malignancy within the last 5 years with exceptions.
• Resting ECG with QTc \> 470 msec or family history of long QT syndrome.
• Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 4 weeks prior to planned start of study treatment.
• Concomitant use of known strong or moderate CYP3A inducers. The required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents. This criterion does not apply to patients in Cohort A.
• Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of MDS/AML.
• Patients with symptomatic uncontrolled brain metastases.
• Major surgery within 2 weeks of starting study treatment. Patients must have recovered from any effects of any major surgery to be considered eligible.
• Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection.
• Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of olaparib.
• Female patients who are pregnant, lactating, or intend to become pregnant during their participation in this study.
• Immunocompromised patients.

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

MeSH Terms

Conditions

Glioma; Cholangiocarcinoma

Interventions

olaparib; durvalumab

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Adenocarcinoma; Carcinoma

Study Officials

• Eric Chen, M.D.

  Princess Margaret Cancer Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eric Chen, M.D.

CONTACT

416-946-2263; eric.chen@uhn.ca

Study Design

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

Study Record Dates

• First Submitted: June 18, 2019
• First Posted: June 19, 2019
• Study Start: December 31, 2019
• Primary Completion: March 31, 2025
• Study Completion: March 31, 2025
• Last Updated: July 18, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)