Small Cell Lung CancerPhase 2NCT03958045
Combination Rucaparib With Nivolumab in Small Cell Lung Carcinoma
A Phase 2 study testing Rucaparib and Nivolumab in people with Small Cell Lung Cancer, run by Zhonglin Hao at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Small Cell Lung Cancer
- What is being tested?
- Rucaparib and Nivolumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Sep 2019to 15 Nov 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 15Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Markey Cancer Center, University of Kentucky
Lexington, Kentucky, 40536
About this study
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
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.
Read the 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).
- Conditions
- Small Cell Lung Cancer
- Being tested
- Rucaparib and Nivolumab
- Keywords
- rucaparib, nivolumab, platinum-sensitive, maintenance, SCLC, immune checkpoint, PARP
- Medical subject headings
- Small Cell Lung Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rucaparib and NivolumabCombination product
Rucaparib (600mg BID) and Nivolumab (480mg IV q4 wk)
| Study group | Role | What they receive |
|---|---|---|
| Patients with Stage IV SCLC | Experimental | Patients with extensive stage (IV) SCLC (small cell lung cancer) Receives: Combination Product: Rucaparib and Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival
Duration (time) of progression-free survival after response to initial platinum-based therapy.
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions from starting maintenance treatment
Measured: 0-2 years
Secondary outcomes (6)
Disease Control Rate
Disease control rate (DCR) is the number of patients who had either complete response (CR, Disappearance of all target lesions), partial response (PR, >=30% decrease in the sum of the longest diameter of target lesions) or stable disease (SD, less than 30% decrease in the sum of the biggest dimension but no more than 20% increase ) per RECICST 1.0 divided by the total number of patients. DOR= (CR+PR+SD)/Total number on trial x 100%.
The timepoints were combined. The best responses were used in calculating disease control rate
Measured: 8 weeks, 16 weeks and 24 weeks post-treatment
Overall Survival
Percentage of surviving participants at 1 and 2 years
Measured: 0-2 years
Objective Response Rate
Objective response rate (ORR) is the proportion of patients with complete response or partial response according to RECIST v1.1. Patients with complete response at baseline will be excluded from ORR analysis.
The timepoints were combined. The best responses were used in calculating objective response rate
Measured: 8 weeks, 16 weeks and 24 weeks post-treatment
Quality of Life Scale Baseline
Quality of life is assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) questionnaire, which probes function and symptoms. Scores range from 0-100. High scores on functional scales represent a high/healthy level of functioning; high scores symptom scales represent a high level of symptomology.
Measured: Baseline
Quality of Life Scale 4 Months
Quality of life is assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) questionnaire, which probes function and symptoms. Scores range from 0-100. High scores on functional scales represent a high/healthy level of functioning; high scores symptom scales represent a high level of symptomology.
Measured: 4 months
Quality of Life Scale at Disease Progression
Quality of life is assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) questionnaire, which probes function and symptoms. Scores range from 0-100. High scores on functional scales represent a high/healthy level of functioning; high scores symptom scales represent a high level of symptomology.
Measured: Disease Progression up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2019
- Study start4 Sep 2019
- Primary completion15 Nov 2022
- Study completion15 Nov 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Small Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Zhonglin Hao
- Sponsor type
- University, hospital or other
- Collaborators
- Clovis Oncology, Inc.
- Responsible party
- Sponsor-investigator, Zhonglin Hao, University of Kentucky
- Investigators
- Zhonglin Hao, MD, Principal investigator, University of Kentucky
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03958045
- Sponsor's protocol ID
- 49346 MCC-18-LUN-107-CLO
- Status last verified
- Oct 2024
- First submitted
- 13 May 2019
- Last updated
- 22 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03958045
- Acronym / sponsor ID
- 49346 MCC-18-LUN-107-CLO
- Conditions
- Small Cell Lung Cancer
- Keywords
- rucaparib, nivolumab, platinum-sensitive, maintenance, SCLC, immune checkpoint, PARP
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Zhonglin HaoUniversity, hospital or other
- Collaborators
- Clovis Oncology, Inc.
- Study start
- 4 Sep 2019 (actual)
- Primary completion
- 15 Nov 2022 (actual)
- Study completion
- 15 Nov 2022 (actual)
- First posted
- 21 May 2019 (actual)
- Results
- Posted 22 Dec 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with Stage IV SCLC | Experimental | Combination Product: Rucaparib and NivolumabPatients with extensive stage (IV) SCLC (small cell lung cancer) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rucaparib and NivolumabRucaparib (600mg BID) and Nivolumab (480mg IV q4 wk) | Combination product | Patients with Stage IV SCLC |
Primary outcome
Progression Free Survival
Time frame: 0-2 years
Duration (time) of progression-free survival after response to initial platinum-based therapy. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions from starting maintenance treatment
6 secondary outcomes
Disease Control Rate
Time frame: 8 weeks, 16 weeks and 24 weeks post-treatment
Overall Survival
Time frame: 0-2 years
Objective Response Rate
Time frame: 8 weeks, 16 weeks and 24 weeks post-treatment
Quality of Life Scale Baseline
Time frame: Baseline
Quality of Life Scale 4 Months
Time frame: 4 months
Quality of Life Scale at Disease Progression
Time frame: Disease Progression up to 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Zhonglin Hao, MD principal investigator
University of Kentucky
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rucaparib and Nivolumab in people with Small Cell Lung Cancer, run by Zhonglin Hao at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression Free Survival (time frame: 0-2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2024.