Carcinoma, Non-small Cell Lung
Conditions
Brief summary
This study will enroll elderly patients with advanced non-small cell lung cancer who are at high risk of developing chemotherapy toxicity (side effects). Patients will receive treatment with either a platinum-based doublet chemotherapy with carboplatin/nab-paclitaxel or single agent nab-paclitaxel of chemotherapy. Response to treatment and treatment toxicity will be compared in the two treatment groups to determine the best treatment strategy for this group of patients.
Detailed description
The primary objective of this trial is to compare the treatment failure-free survival rate in high-risk elderly patients, identified by geriatric assessment, treated with either a platinum-based doublet chemotherapy with carboplatin/nab-paclitaxel or single agent nab-paclitaxel in advanced non-small cell lung cancer. Treatment failure-free survival is the most appropriate primary outcome as it captures excessive toxicity due to chemotherapy in addition to death and disease progression. The secondary objectives are to evaluate grade 3-5 toxicities, overall response rate, progression free survival, symptom assessment, and overall survival between the two randomization arms.
Interventions
DRUGCarboplatin
DRUGNab-paclitaxel
Sponsors
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
71 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patient able and willing to comply with study procedures as per protocol, including the geriatric assessment at the time of study enrollment. 2. Patient able to understand and willing to sign and date the written voluntary informed consent form (ICF) at screening visit prior to any protocol-specific procedures. 3. Patients must have histological or cytological confirmed primary non-small cell lung cancer (adenocarcinoma, large cell carcinoma, squamous, or unspecified). Disease must be stage IV Non-Small Cell Lung Cancer (NSCLC). Disease may be either newly diagnosed or recurrent after previous surgery and/or irradiation. Primary or metastatic site for biopsy is allowed 4. Patients may have measurable or non-measurable disease documented by CT or MRI. The CT from a combined PET/CT may be used to document only non-measurable disease. Measurable disease must be assessed within 30 days prior to registration per response evaluation criteria in solid tumors (RECIST) v1.1. Pleural effusions, ascites and laboratory parameters are not acceptable as the only evidence of disease. Non- measurable disease must be assessed within 30 days prior to registration. All disease must be assessed and documented on the Baseline Tumor Assessment Form. 5. Prior chemotherapy for curative intent is permitted providing the cytotoxic chemotherapy was completed ≥12 months prior to enrollment. Patients must have a CT or MRI scan of the brain to evaluate for CNS disease within 30 days prior to registration. Patient must not have brain metastases unless: (1) metastases have been treated and have remained controlled for at least two weeks following treatment, AND (2) patient has no residual neurological dysfunction off corticosteroids for at least 1 day. Any radiation therapy completed prior to chemotherapy, except gamma-knife radiosurgery, 1 week prior to chemotherapy. 6. Age \>70 years of age at time of signing of the informed consent form. 7. Life expectancy of greater than 12 weeks. 8. ECOG performance status 0-2 (See Appendix A) 9. Patients must have a comprehensive geriatric assessment and chemotherapy toxicity assessment score between 7-17 (See Appendix B, D) 10. Patients must have normal organ and marrow function as defined below: * Leukocytes \>3,000/mcL * ANC \> 1,500 cells/mm3Hemoglobin \> 9.0g/dL * Platelets \>100,000 cells/mm3 * Total bilirubin \< 1.5 mg/dL (unless there is a known history of Gilberts Syndrome). * AST(SGOT)/ALT(SGPT) ≤2.5 X institutional upper limit of normal * Alkaline phosphatase \< 2.5 X upper limit of normal in the absence of liver or bone metastasis, or ≤ 5.0 × upper limit of normal range if bone or liver metastases * Creatinine clearance \>25 mL/min or creatinine \<1.5 mg/dL 11. HIV-positive patients on combination antiretroviral therapy are eligible if they have been on ARVs for ≥6 months and undetectable viral loads. 12. Patients must not have documented evidence of acute hepatitis or have an active or uncontrolled infection. 13. No other priormalignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years. 14. Ability to understand and the willingness to sign a written informed consent document in English or a Spanish consent short form. If language other than English or Spanish, then interpreter will be used to sign English consent form. 15. Patients must have \< Grade 2 pre-existing peripheral neuropathy (per CTCAE)
Exclusion criteria
1. Patients who have had palliative chemotherapy prior to entering the study \<12 months from enrollment or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. 2. Patients may not be receiving any other investigational agents or have received immunotherapy. 3. Known EGFR or ALK mutated disease (molecular testing not required prior to study entry) 4. History of allergic reactions attributed to compounds of similar chemical or biologic composition to carboplatin, or nab-paclitaxel. 5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. 6. Preexisting peripheral neuropathy of Grade 2, 3, or 4 (per Common Terminology Criteria for Adverse Events v4.0) 7. Evidence of active brain metastases, including leptomeningeal involvement (prior evidence of brain metastasis are permitted only if treated and stable and off therapy for ≥ 2 weeks prior to signing Informed consent form. Magnetic Resonance Imaging of the brain (or Computed Tomography scan w/contrast) is preferred for diagnosis.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Treatment Failure-free Survival | 90 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | start of treatment to disease progression/recurrence, up to 12 months | — |
| Progression-free Survival | start of treatment to disease progression, up to 12 months | — |
| Overall Survival | Up to 12 months | — |
| Grade 3-5 Adverse Events | Up to week 13 | Adverse events were characterized using Common Terminology Criteria for Adverse Events (CTCAE) |
| Symptom Assessment (Measured by FACT-L Symptom Assessment Scale) | baseline | The FACT-L is measure of symptoms associated with lung cancer. The higher the score, the greater the symptoms. A maximum score of 136 could be obtained. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Platinum-based Doublet Chemotherapy * Carboplatin AUC 5 30 minute infusion IV on day 1
* Nab-paclitaxel 100mg/mg2 30 minute infusion IV on days 1, 8 of a 21 day cycle
Carboplatin
Nab-paclitaxel | 1 |
| Single Agent Chemotherapy -Nab-paclitaxel 100mg/mg2 30 minute infusion IV on days 1, 8 of a 21 day cycle
Nab-paclitaxel | 2 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 2 |
Baseline characteristics
| Characteristic | Total | Platinum-based Doublet Chemotherapy | Single Agent Chemotherapy |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 1 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment United States | 3 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 2 | 1 / 1 |
| other Total, other adverse events | 2 / 2 | 0 / 1 |
| serious Total, serious adverse events | 1 / 2 | 0 / 1 |
Outcome results
Primary
Treatment Failure-free Survival
Time frame: 90 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Platinum-based Doublet Chemotherapy | Treatment Failure-free Survival | 0 Participants |
| Single Agent Chemotherapy | Treatment Failure-free Survival | 0 Participants |
Secondary
Grade 3-5 Adverse Events
Adverse events were characterized using Common Terminology Criteria for Adverse Events (CTCAE)
Time frame: Up to week 13
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Platinum-based Doublet Chemotherapy | Grade 3-5 Adverse Events | Overall | 0 Participants |
| Platinum-based Doublet Chemotherapy | Grade 3-5 Adverse Events | Grade 3 | 0 Participants |
| Platinum-based Doublet Chemotherapy | Grade 3-5 Adverse Events | Grade 4 | 0 Participants |
| Platinum-based Doublet Chemotherapy | Grade 3-5 Adverse Events | Grade 5 | 0 Participants |
| Single Agent Chemotherapy | Grade 3-5 Adverse Events | Grade 5 | 0 Participants |
| Single Agent Chemotherapy | Grade 3-5 Adverse Events | Overall | 2 Participants |
| Single Agent Chemotherapy | Grade 3-5 Adverse Events | Grade 4 | 0 Participants |
| Single Agent Chemotherapy | Grade 3-5 Adverse Events | Grade 3 | 2 Participants |
Secondary
Overall Response Rate
Time frame: start of treatment to disease progression/recurrence, up to 12 months
Population: The study was terminated after only 3 patients were randomized and all 3 did not respond to treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Platinum-based Doublet Chemotherapy | Overall Response Rate | 0 Participants |
| Single Agent Chemotherapy | Overall Response Rate | 0 Participants |
Secondary
Overall Survival
Time frame: Up to 12 months
Population: The study was terminated after only 3 patients were randomized and all 3 did not respond to treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Platinum-based Doublet Chemotherapy | Overall Survival | 0 Participants |
| Single Agent Chemotherapy | Overall Survival | 0 Participants |
Secondary
Progression-free Survival
Time frame: start of treatment to disease progression, up to 12 months
Population: The study was terminated after only 3 patients were randomized and all 3 did not respond to treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Platinum-based Doublet Chemotherapy | Progression-free Survival | 0 Participants |
| Single Agent Chemotherapy | Progression-free Survival | 0 Participants |
Secondary
Symptom Assessment (Measured by FACT-L Symptom Assessment Scale)
The FACT-L is measure of symptoms associated with lung cancer. The higher the score, the greater the symptoms. A maximum score of 136 could be obtained.
Time frame: baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Platinum-based Doublet Chemotherapy | Symptom Assessment (Measured by FACT-L Symptom Assessment Scale) | 89 units on a scale | — |
| Single Agent Chemotherapy | Symptom Assessment (Measured by FACT-L Symptom Assessment Scale) | 44 units on a scale | Standard Deviation 26.9 |
Secondary
Symptom Assessment (Measured by FACT-L Symptom Assessment Scale)
The higher the score, the greater the symptoms. The FACT-L is measure of symptoms associated with lung cancer. The higher the score, the greater the symptoms. A maximum score of 136 could be obtained. Symptoms were measured following 2 21-day cycles of chemotherapy.
Time frame: week 6
Population: Only 2 patients were assessed at this timepoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Single Agent Chemotherapy | Symptom Assessment (Measured by FACT-L Symptom Assessment Scale) | 60.5 units on a scale | Standard Deviation 19.1 |
Secondary
Symptom Assessment (Measured by FACT-L Symptom Assessment Scale)
The FACT-L is measure of symptoms associated with lung cancer. The higher the score, the greater the symptoms. Symptoms were measured following 4 21-day cycles of chemotherapy.
Time frame: week 12
Population: The study was terminated after only 3 patients were randomized and all 3 did not respond to treatment, these data were not collected at week 12