Clinical trial NCT03958045: Combination Rucaparib With Nivolumab in Small Cell Lung Carcinoma
Official title: Phase II Study of Combination Rucaparib With Nivolumab in Platinum-Sensitive Small Cell Lung Carcinoma Patients as Maintenance After Induction Therapy With Platinum Doublet
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Small Cell Lung Cancer
Keywords: rucaparib
nivolumab
platinum-sensitive
maintenance
SCLC
immune checkpoint
PARP
Lead sponsor: University of Kentucky
Sponsor class: OTHER
Collaborators: name: Clovis Oncology, Inc.
First posted: 2019-05-21
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate survival and response rate of the combination rucaparib and nivolumab as maintenance therapy in platinum-sensitive small cell lung carcinoma.

Detailed description: Small cell lung cancer (SCLC) is one of the most aggressive malignancies with a 5-year survival rate of less than 7%. SCLC is characterized by rapid doubling time, high growth fraction and early development of widespread metastases. SCLC accounts for roughly 93% of all high-grade neuroendocrine carcinomas. The prognosis for SCLC is extremely poor with a median survival less than a year for extensive-stage disease. Therapeutic options have not advanced significantly in over two decades, with frontline treatment consisting of platinum doublet therapy for 3-6 cycles. While most patients show an initial favorable response to Carboplatin/cisplatin + etoposide, this response is usually short-lived. Most patients relapse with resistant disease between 3 to 6 months after completion of initial chemotherapy.

Based on preclinical data supporting the role of immune checkpoint and PARP (poly ADP ribose polymerase ) inhibitors in SCLC, combining nivolumab and rucaparib has the potential to prolong progression-free survival and overall survival. These two classes of drugs have non-overlapping toxicities. This novel combination has not been tried in a front-line maintenance setting for SCLC.

Eligible patients will have pathological (biopsy) or cytologically confirmed stage IV SCLC, and have achieved either partial or complete response post frontline chemotherapy with platinum doublet. Patients will be treated with combination rucaparib and nivolumab. The recommended starting dose of rucaparib as a continuously administered oral monotherapy is 600 mg BID. Nivolumab will be administered as an intravenous infusion once every 4 weeks at a fixed dose of 480 mg. In the absence of treatment delays due to adverse event(s), treatment may continue for 24 months.

Progression-free survival, overall survival, disease control rates, objective response rate, quality of life, and tumor mutation burden will be evaluated during this study (up to 2 years).

Eligibility criteria: Inclusion Criteria

* Patients with histologically or cytologically confirmed stage IV, extensive stage, small cell lung cancer who achieved either partial or complete remission per RECIST 1.1 post frontline chemotherapy with platinum doublet (Cisplatin or Carboplatin/etoposide).
* Enrollment is within 6 weeks of last (4th cycle) of chemotherapy.
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
* Adequate Bone Marrow Function
* Adequate Hepatic Function

Exclusion Criteria

* Prior therapy with any antibody/drug targeting T-cell co-regulatory proteins (immune checkpoints)
* Major surgery within 4 weeks of initiation of study medication.
* Current use of (some) immunosuppressants
* Active infection requiring systemic therapy
* HIV/AIDS
* Hepatitis B virus or hepatitis C virus infection at screening
* Autoimmune disease
* Persisting toxicity related to prior therapy
* Pregnancy
* Vaccination (except inactive) within 4 weeks of the first dose of nivolumab
* Hypersensitivity to the study drugs
* Cardiovascular disease
* Untreated central nervous system (CNS) metastases or leptomeningeal carcinomatosis
* (Some) active secondary malignancy
* Active pneumonitis or interstitial lung disease

Primary outcomes:
measure: Progression Free Survival
timeFrame: 0-2 years
Secondary outcomes:
measure: Disease Control Rate
timeFrame: 8 weeks, 16 weeks and 24 weeks post-treatment
measure: Overall Survival
timeFrame: 0-2 years
measure: Objective Response Rate
timeFrame: 8 weeks, 16 weeks and 24 weeks post-treatment
measure: Quality of Life Scale Baseline
timeFrame: Baseline
measure: Quality of Life Scale 4 Months
timeFrame: 4 months
measure: Quality of Life Scale at Disease Progression
timeFrame: Disease Progression up to 2 years
Other outcomes:
measure: Tumor Mutation Burden
timeFrame: 0-3 years
measure: PD-L1 CPS
timeFrame: 0-3 years
Locations:
city: Lexington
country: United States
facility: Markey Cancer Center, University of Kentucky
state: Kentucky
Study officials:
affiliation: University of Kentucky
name: Zhonglin Hao, MD
role: PRINCIPAL_INVESTIGATOR
References: