Anatomic Stage IV Breast Cancer AJCC v8, Metastatic Triple-Negative Breast Carcinoma
Conditions
Brief summary
This phase II study assesses the efficacy of the combination of olaparib with durvalumab, selumetinib, or capivasertib or ceralasertib alone in the treatment of patients with metastatic triple negative breast cancer (TNBC). Olaparib may stop growth of tumor cells by inhibiting some of the enzymes (ADP ribose polymerase \[PARP\]) needed for cell growth. Durvalumab, a monoclonal antibody, inhibits the growth and spread of tumors by stimulating the patient's antitumor immune response. Selumetinib, capivasertib, and ceralasertib are inhibitor drugs that may stop the growth of tumor cells by blocking some of the enzymes (MEK, AKT, ATR) needed for cell growth. Giving olaparib together with durvalumab, selumetinib, or capivasertib or giving ceralasertib alone may provide an effective method to treat patients with metastatic triple negative breast cancer.
Detailed description
PRIMARY OBJECTIVE: I. Assess overall response to treatment. SECONDARY OBJECTIVES: I. Assess participant benefit from treatment. II. Determine the time to disease progression following response to study therapy. III. Determine time to first disease progression or death of participants enrolled on the study. IV. Determine survival of participants enrolled on the study. V. Assess safety and tolerability of the proposed therapy. EXPLORATORY OBJECTIVES: I. To assess a change in quality of life (QOL) as measured by European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) in each treatment arm. II. To assess a change in QOL as measured by Breast Cancer-Specific Quality of Life Questionnaire (QLQ-BR23) in each treatment arm. III. Examine response rates depending on tumor characteristics. IV. Identify predictive biomarkers of sensitivity to therapy. V. Identify emerging mechanism of resistance to therapy. VI. Determine changes in tumor cells and the tumor microenvironment induced by PARP inhibitors. OUTLINE: This is an open-label, multi-arm phase II study of olaparib in combination with durvalumab, selumetinib, or capivasertib, or ceralasertib monotherapy. LEAD IN: Patients with biopsy proven TNBC undergo a pre-treatment biopsy. At the 2 week mark, patients then undergo a repeat on-treatment biopsy. Patients also receive olaparib orally (PO) twice daily (BID) on days 1-28 for one cycle. Treatment repeats every 28 days for up to 1 cycle in the absence of disease progression or unacceptable toxicity. Patients are then assigned to 1 of 4 arms based on predefined molecular tumor characteristics. ARM I: Patients receive olaparib PO BID on days 1-28 of each cycle and durvalumab intravenously (IV) over 1 hour on day 1 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. ARM II: Patients receive olaparib PO BID on days 1-28 of each cycle and selumetinib PO BID on days 1-28 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. ARM III: Patients receive olaparib PO BID on days 1-28 of each cycle and capivasertib PO BID 4 days on and 3 days off of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. ARM IV: Patients receive ceralasertib PO BID on days 1-14 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. At the completion of all on-study procedures, patients are followed up every 6 months for disease and survival outcomes up to 1 year. Patients will be asked to submit an optional tumor biopsy in the event of disease progression.
Interventions
PROCEDUREBiopsy
Undergo biopsy
DRUGCapivasertib
Given PO (orally)
DRUGCeralasertib
Given PO (orally)
BIOLOGICALDurvalumab
Given IV (infusion)
DRUGOlaparib
Given PO (orally)
OTHERQuality-of-Life Assessment
Ancillary studies
DRUGSelumetinib
Given PO (orally)
Sponsors
Gordon Mills, MD, PhD
AstraZeneca
Oregon Health and Science University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Ability to understand and the willingness to sign a written informed consent document * Participants are \>= 18 years old at time of informed consent. * Metastatic TNBC, as defined by: * Estrogen receptor (ER) and progesterone receptor (PR) negative as defined as ER \< 10% and PR \< 10% by immunohistochemistry according to American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines for hormone receptor testing * HER2 non-amplified per ASCO/CAP guidelines, defined as: * IHC score 0/1+ * IHC 2+ and in situ hybridization (ISH) non-amplified with a ratio of HER2 to CEP17 \< 2.0, and if reported, average HER2 gene copy number \< 4 signals/cells; or * ISH non-amplified with a ratio of HER2 to CEP17 \<2.0, and if reported, average HER2 gene copy number \< 4 signals/cells * Participants with or without germline BRCA mutated TNBC are eligible for study participation * Participants must have at least one measurable site of disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 that is amenable to biopsy * Prior therapies for metastatic breast cancer * Frontline patients who have not received prior systemic therapy for metastatic breast cancer are eligible * Patients who have received =\< 2 prior chemotherapy regimens for metastatic breast cancer are eligible * Participants must have fully recovered from the acute toxic effects of all prior treatment to grade 1 or less, except alopecia which is allowed * Participants must have a life expectancy \>= 16 weeks * Participant must have Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 * Participant must consent to undergo a pre-treatment screening biopsy for enrollment and subsequent biomarker analyses * Participants must consent to undergo one mandatory on-study tumor biopsy following a 2-week induction treatment of olaparib. A second on-study biopsy at time of disease progression is optional, but not mandatory * Participants must not have received previous treatment with PARP inhibitors, including olaparib * Hemoglobin \>= 10.0 g/dL (measured within 28 days prior to administration of study treatment) * Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L (measured within 28 days prior to administration of study treatment) * Platelet count \>= 100 x 10\^9/L (measured within 28 days prior to administration of study treatment) * Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (measured within 28 days prior to administration of study treatment) * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal unless liver metastases are present in which case they must be =\< 5 x ULN (measured within 28 days prior to administration of study treatment) * Participants must have creatinine clearance estimated of \>= 51 mL/min using the Cockcroft-Gault equation or based on a 24 hour urine test (measured within 28 days prior to administration of study treatment) * Participants of childbearing potential must have a negative urine or serum pregnancy test within 28 days of study treatment and confirmed on Day 1 prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required * Participants of childbearing potential agree to use adequate methods of contraception, upon signing of informed consent through: * 6 months after the last dose with olaparib, * 3 months after the last dose with durvalumab, * 1 week after the last dose with selumetinib, * 1 month after the last dose with capivasertib, * 1 month after the last dose with ceralasertib. * Participants of childbearing potential are those who are not proven postmenopausal. Postmenopausal is defined as: * Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments * Luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the post-menopausal range for women under 50 * Radiation-induced oophorectomy with last menses \>1 year ago * Chemotherapy-induced menopause with \>1 year interval since last menses * Surgical sterilization (bilateral oophorectomy or hysterectomy) * Sperm-producing participants must use a condom during treatment and for 3 months after the last dose of olaparib when having sexual intercourse with a pregnant partner or with an individual of childbearing potential. Partners of sperm-producing participants should also use a highly effective form of contraception if they are of childbearing potential * Sperm-producing participants assigned to receive capivasertib must use a condom during treatment and for 4 months after the last dose of capivasertib when having sexual intercourse with a pregnant partner or with an individual of childbearing potential
Exclusion criteria
* Any concurrent anticancer treatment * Individuals in the follow-up phase of a prior investigational study may participate as long as it has been 4 weeks since last dose of the previous investigational agent or device * Concurrent use of hormonal therapy for non-cancer related conditions (e.g., hormone replacement therapy) is allowed * Participant's with tumors showing androgen receptor (AR) \>= 80% by immunohistochemistry are excluded * Other malignancy unless curatively treated with no evidence of disease for \>= 5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), stage 1, grade 1 endometrial carcinoma. Participants with a personal history of treated early stage breast cancer whose natural history or treatment does not have the potential to interfere with the safety or efficacy endpoints of the trial, per investigator assessment, are eligible * Participants with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) * Participant received prior anticancer therapy such as targeted therapies, or systemic chemotherapy or radiation (except for palliative reasons) within the past 3 weeks, or 5 half-lives, whichever is shorter, prior to first day of treatment * Participants with known active central nervous system (CNS) metastases and/or carcinomatous meningitis * Patients with brain metastases may participate provided they do not have symptomatic uncontrolled disease. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment. (note: a scan to confirm the absence of brain metastases is not required) * Patients with spinal cord compression are not eligible unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days * Patients with carcinomatous meningitis are not eligible * Concomitant use of known strong CYP3A inhibitors (e.g., ketoconazole, posaconazole), or strong CYP3A inducers (e.g., phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout period prior to starting study intervention treatment is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents * Major surgery within 4 weeks of starting study treatment and patients must have recovered from any effects of any major surgery * Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT) * Patients that are immunocompromised, including those with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness are not eligible for participation * Note: HIV-infected participants on effective anti-retroviral therapy with undetectable viral load for \>= 6 months are eligible for this trial provided that there is minimal interactions or overlapping toxicity of the antiretroviral therapy with their study intervention. Refer to drug-specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | End of treatment (Up to 24 months) | Using the efficacy analysis set, the estimate of ORR will be measured independently for each treatment arm and reported with 95% exact confidence interval. Participants who, within their respective treatment arm, achieve a complete response (CR) or a partial response (PR) that is confirmed on a second scan at least 4 weeks later on the current protocol will be qualified as achieving a response, and will count towards the ORR measurement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Benefit Rate (CBR) | End of treatment (Up to 24 months) | An estimate of CBR will be measured independently for each treatment arm and reported with 95% exact confidence interval. Participants who, within their respective treatment arm, achieve a CR, PR, or stable disease (SD) for at least 6 months on the current protocol will be qualified as deriving benefit from therapy, and will count towards the CBR measurement. |
| Duration of Response (DOR) | Duration of response was calculated from date of PR/CR (whichever occurred earlier) to EOT. | The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented taking as reference for progressive disease the smallest measurements recorded since the treatment started. The duration of overall CR is measured from the time measurement criteria are first met for CR until the first date that progressive disease is objectively documented. If a participant dies, irrespective of cause, without documentation of recurrent or progressive disease beforehand, then the date of death will be used to denote the response end date. |
| Progression-free Survival (PFS) | Progression or death (any cause) up to 1 year post treatment | PFS is defined as the time after having completed at least one cycle of olaparib monotherapy to the first of either recurrence or relapse (anywhere in the body) or death at the time of last follow-up at 12-months. The estimated distribution of the PFS for each treatment will be plotted using Kaplan Meier curves and reported with median survival and 95% confidence intervals if available. |
| Overall Survival (OS) | Death (any cause) up to 1 year post treatment | OS is defined as the time after having completed at least one cycle of olaparib monotherapy up to 6 months following the completion of on-study treatment to the date of death or last follow-up at 12 months. The estimated distribution of the OS for each treatment will be plotted using Kaplan Meier curves and reported with median survival and 95% confidence intervals if available. |
| Incidence of Grade 3+ Acute Toxicity: # of Occurrences | Up to 3 months post treatment | Will be assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. The incidence of having grade 3+ acute toxicity will be determined for participants with triple negative breast cancer (TNBC) that received at least one dose of olaparib and/or durvalumab., selumetinib, capivasertib, or ceralasertib. The 95% confidence interval will be reported with the point estimate of toxicity rate. |
| Incidence of Grade 3+ Acute Toxicity: # of Participants | Up to 3 months post treatment | Will be assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. The incidence of having grade 3+ acute toxicity will be determined for participants with triple negative breast cancer (TNBC) that received at least one dose of olaparib and/or durvalumab., selumetinib, capivasertib, or ceralasertib. The 95% confidence interval will be reported with the point estimate of toxicity rate. |
Countries
United States
Contacts
STUDY_CHAIRGordon Mills, MD, PhD
OHSU Knight Cancer Institute
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm I (Olaparib, Durvalumab) Patients receive olaparib PO BID on days 1-28 of each cycle and durvalumab intravenously (IV) over 1 hour on day 1 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles.
Biopsy: Undergo biopsy
Durvalumab: Given IV (infusion)
Olaparib: Given PO (orally)
Quality-of-Life Assessment: Ancillary studies | 24 |
| Arm II (Olaparib, Selumetinib) Patients receive olaparib PO BID on days 1-28 of each cycle and selumetinib PO BID on days 1-28 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles.
Biopsy: Undergo biopsy
Olaparib: Given PO (orally)
Quality-of-Life Assessment: Ancillary studies
Selumetinib: Given PO (orally) | 0 |
| Arm III (Olaparib, Capivasertib) Patients receive olaparib PO BID on days 1-28 of each cycle and capivasertib PO BID 4 days on and 3 days off of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles.
Biopsy: Undergo biopsy
Capivasertib: Given PO (orally)
Olaparib: Given PO (orally)
Quality-of-Life Assessment: Ancillary studies | 0 |
| Arm IV (Ceralasertib) Patients receive ceralasertib PO BID on days 1-14 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles.
Biopsy: Undergo biopsy
Ceralasertib: Given PO (orally)
Quality-of-Life Assessment: Ancillary studies | 0 |
| Total | 24 |
Baseline characteristics
| Characteristic | Arm I (Olaparib, Durvalumab) | Total |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants | 20 Participants |
| Age, Continuous | 54 Years | 54 Years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 21 Participants | 21 Participants |
| Region of Enrollment United States | 24 participants | 24 participants |
| Sex: Female, Male Female | 24 Participants | 24 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 19 / 24 | 0 / 0 | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 24 / 24 | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 2 / 24 | 0 / 0 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Objective Response Rate (ORR)
Using the efficacy analysis set, the estimate of ORR will be measured independently for each treatment arm and reported with 95% exact confidence interval. Participants who, within their respective treatment arm, achieve a complete response (CR) or a partial response (PR) that is confirmed on a second scan at least 4 weeks later on the current protocol will be qualified as achieving a response, and will count towards the ORR measurement.
Time frame: End of treatment (Up to 24 months)
Population: No participants were enrolled in Arm II - Arm IV.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (olaparib, durvalumab) | Objective Response Rate (ORR) | 6 Participants |
Secondary
Clinical Benefit Rate (CBR)
An estimate of CBR will be measured independently for each treatment arm and reported with 95% exact confidence interval. Participants who, within their respective treatment arm, achieve a CR, PR, or stable disease (SD) for at least 6 months on the current protocol will be qualified as deriving benefit from therapy, and will count towards the CBR measurement.
Time frame: End of treatment (Up to 24 months)
Population: No participants were enrolled in Arm II - Arm IV.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (olaparib, durvalumab) | Clinical Benefit Rate (CBR) | 10 Participants |
Secondary
Duration of Response (DOR)
The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented taking as reference for progressive disease the smallest measurements recorded since the treatment started. The duration of overall CR is measured from the time measurement criteria are first met for CR until the first date that progressive disease is objectively documented. If a participant dies, irrespective of cause, without documentation of recurrent or progressive disease beforehand, then the date of death will be used to denote the response end date.
Time frame: End of treatment (Up to 24 months)
Secondary
Incidence of Grade 3+ Acute Toxicity
Will be assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. The incidence of having grade 3+ acute toxicity will be determined for participants with triple negative breast cancer (TNBC) that received at least one dose of olaparib and/or durvalumab., selumetinib, capivasertib, or ceralasertib. The 95% confidence interval will be reported with the point estimate of toxicity rate.
Time frame: Up to 3 months post treatment
Population: No participants were enrolled in Arm II - Arm IV.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I (olaparib, durvalumab) | Incidence of Grade 3+ Acute Toxicity | 16 participants |
Secondary
Incidence of Grade 3+ Acute Toxicity
Will be assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. The incidence of having grade 3+ acute toxicity will be determined for participants with triple negative breast cancer (TNBC) that received at least one dose of olaparib and/or durvalumab., selumetinib, capivasertib, or ceralasertib. The 95% confidence interval will be reported with the point estimate of toxicity rate.
Time frame: Up to 3 months post treatment
Population: No participants were enrolled in Arm II - Arm IV.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I (olaparib, durvalumab) | Incidence of Grade 3+ Acute Toxicity | 46 occurrences |
Secondary
Overall Survival (OS)
OS is defined as the time after having completed at least one cycle of olaparib monotherapy up to 6 months following the completion of on-study treatment to the date of death or last follow-up at 12 months. The estimated distribution of the OS for each treatment will be plotted using Kaplan Meier curves and reported with median survival and 95% confidence intervals if available.
Time frame: Death (any cause) up to 1 year post treatment
Population: No participants were enrolled in Arm II - Arm IV.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I (olaparib, durvalumab) | Overall Survival (OS) | 15.5 months |
Secondary
Progression-free Survival (PFS)
PFS is defined as the time after having completed at least one cycle of olaparib monotherapy to the first of either recurrence or relapse (anywhere in the body) or death at the time of last follow-up at 12-months. The estimated distribution of the PFS for each treatment will be plotted using Kaplan Meier curves and reported with median survival and 95% confidence intervals if available.
Time frame: Progression or death (any cause) up to 1 year post treatment
Population: No participants were enrolled in Arm II - Arm IV.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arm I (olaparib, durvalumab) | Progression-free Survival (PFS) | 4.8 months |
Other Pre-specified
Change in QOL as Measured by EORTC QLQBR23
The QOL measures will be summarized and presented over time graphically using box and spaghetti plots, in addition to summary tables. Mixed effect model will be further used to analyze the longitudinal data. For each instrument, the analysis will include all cycles for which at least 25% of participants in each arm that have an assessment. QLQBR23 is a 23-item instrument that measures symptoms and side effects related to treatment, body image, sexuality, and future perspective specific to breast cancer patients. QLQBR23 has high internal consistency (Cronbach's a = 0.71-0.90), can distinguish between patients based on disease stage, performance status, treatment modality, or prior surgery, and is sensitive to change over time. The EORTC QLQ-BR23 data will be scored as described by the EORTC scoring manual.
Time frame: Baseline to end of treatment (Up to 24 months)
Other Pre-specified
Change in Quality of Life (QOL) as Measured by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)
The QOL measures will be summarized and presented over time graphically using box and spaghetti plots, in addition to summary tables. Mixed effect model will be further used to analyze the longitudinal data. For each instrument, the analysis will include all cycles for which at least 25% of participants in each arm that have an assessment. QLQC30 is a 30-item measure and yields scores for 5 functional scales (physical, role, cognitive, social, and emotional), 3-symptom scales (nausea, pain, and fatigue), a global health and QOL scale, and perceived financial impact of treatment. QLQC30 can distinguish patients according to performance status and is the most commonly used QOL instrument in oncology research. Data from the EORTC QLQ-C30 instrument will be scored as previously described by Aaronson et al.
Time frame: Baseline to end of treatment (Up to 24 months)