Small Cell Lung Cancer
Conditions
Keywords
rucaparib, nivolumab, platinum-sensitive, maintenance, SCLC, immune checkpoint, PARP
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).
Interventions
COMBINATION_PRODUCTRucaparib and Nivolumab
Rucaparib (600mg BID) and Nivolumab (480mg IV q4 wk)
Sponsors
Clovis Oncology, Inc.
Zhonglin Hao
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate | 8 weeks, 16 weeks and 24 weeks post-treatment | 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 |
| Overall Survival | 0-2 years | Percentage of surviving participants at 1 and 2 years |
| Objective Response Rate | 8 weeks, 16 weeks and 24 weeks post-treatment | 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 |
| Quality of Life Scale 4 Months | 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. |
| Quality of Life Scale at Disease Progression | Disease Progression up to 2 years | 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. |
| Quality of Life Scale Baseline | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Tumor Mutation Burden | 0-3 years | Correlate tumor mutation burden with treatment response. |
| PD-L1 CPS | 0-3 years | A combined positive score (CPS) for Programmed Death Ligand 1 (PD-L1) will be derived from immunohistochemical analysis of tumor tissue. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Patients With Stage IV SCLC Patients with extensive stage (IV) SCLC (small cell lung cancer)
Rucaparib and Nivolumab: Rucaparib (600mg BID) and Nivolumab (480mg IV q4 wk) | 33 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Patients With Stage IV SCLC |
|---|---|
| Age, Continuous | 59.8 years STANDARD_DEVIATION 7.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 28 Participants |
| Region of Enrollment United States | 33 Participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 16 / 33 |
| other Total, other adverse events | 33 / 33 |
| serious Total, serious adverse events | 12 / 33 |
Outcome results
Primary
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
Time frame: 0-2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Patients With Stage IV SCLC | Progression Free Survival | 11 months |
Secondary
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
Time frame: 8 weeks, 16 weeks and 24 weeks post-treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Patients With Stage IV SCLC | Disease Control Rate | 33.3 percentage of participants |
Secondary
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
Time frame: 8 weeks, 16 weeks and 24 weeks post-treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Patients With Stage IV SCLC | Objective Response Rate | 4 Participants |
Secondary
Overall Survival
Percentage of surviving participants at 1 and 2 years
Time frame: 0-2 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Patients With Stage IV SCLC | Overall Survival | 1 year | 93.55 percentage of participants |
| Patients With Stage IV SCLC | Overall Survival | 2 years | 52.82 percentage of participants |
Secondary
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.
Time frame: 4 months
Population: Only 10 participants completed the scale at the 4 month timepoint
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Patients With Stage IV SCLC | Quality of Life Scale 4 Months | Physical Functioning | 70.5 units on a scale | Standard Deviation 14.7 |
| Patients With Stage IV SCLC | Quality of Life Scale 4 Months | Role Functioning | 65 units on a scale | Standard Deviation 30.9 |
| Patients With Stage IV SCLC | Quality of Life Scale 4 Months | Emotional Functioning | 75.6 units on a scale | Standard Deviation 24.1 |
| Patients With Stage IV SCLC | Quality of Life Scale 4 Months | Cognitive Functioning | 78.3 units on a scale | Standard Deviation 26.1 |
| Patients With Stage IV SCLC | Quality of Life Scale 4 Months | Social Functioning | 73.3 units on a scale | Standard Deviation 25.1 |
| Patients With Stage IV SCLC | Quality of Life Scale 4 Months | Global health status | 65.8 units on a scale | Standard Deviation 14.4 |
Secondary
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.
Time frame: Disease Progression up to 2 years
Population: Only 2 subjects have completed the questionnaire at progression. Due to this small sample size, the standard deviation can be 0 if the responses happen to be the same for questions related to physical functioning
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Patients With Stage IV SCLC | Quality of Life Scale at Disease Progression | Emotional Functioning | 45.8 units on a scale | Standard Deviation 41.2 |
| Patients With Stage IV SCLC | Quality of Life Scale at Disease Progression | Physical Functioning | 66.7 units on a scale | Standard Deviation 0 |
| Patients With Stage IV SCLC | Quality of Life Scale at Disease Progression | Role Functioning | 41.7 units on a scale | Standard Deviation 35.4 |
| Patients With Stage IV SCLC | Quality of Life Scale at Disease Progression | Cognitive Functioning | 41.7 units on a scale | Standard Deviation 35.4 |
| Patients With Stage IV SCLC | Quality of Life Scale at Disease Progression | Social Functioning | 50 units on a scale | Standard Deviation 23.6 |
| Patients With Stage IV SCLC | Quality of Life Scale at Disease Progression | Global health status | 50 units on a scale | Standard Deviation 23.6 |
Secondary
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.
Time frame: Baseline
Population: 3 participants did not answer all questions
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Patients With Stage IV SCLC | Quality of Life Scale Baseline | Physical Functioning | 76.1 units on a scale | Standard Deviation 17 |
| Patients With Stage IV SCLC | Quality of Life Scale Baseline | Role Functioning | 69.3 units on a scale | Standard Deviation 27.8 |
| Patients With Stage IV SCLC | Quality of Life Scale Baseline | Emotional Functioning | 78.1 units on a scale | Standard Deviation 19.6 |
| Patients With Stage IV SCLC | Quality of Life Scale Baseline | Cognitive Functioning | 81 units on a scale | Standard Deviation 22.6 |
| Patients With Stage IV SCLC | Quality of Life Scale Baseline | Social Functioning | 72.4 units on a scale | Standard Deviation 26.1 |
| Patients With Stage IV SCLC | Quality of Life Scale Baseline | Global health status | 65.2 units on a scale | Standard Deviation 17.7 |
Other Pre-specified
PD-L1 CPS
A combined positive score (CPS) for Programmed Death Ligand 1 (PD-L1) will be derived from immunohistochemical analysis of tumor tissue.
Time frame: 0-3 years
Other Pre-specified
Tumor Mutation Burden
Correlate tumor mutation burden with treatment response.
Time frame: 0-3 years