Advanced Lymphoma, Advanced Malignant Solid Neoplasm, Hematopoietic and Lymphoid Cell Neoplasm, Refractory Lymphoma, Refractory Malignant Solid Neoplasm, Refractory Multiple Myeloma
Conditions
Brief summary
This phase II MATCH treatment trial identifies the effects of AZD5363 in patients whose cancer has a genetic change called AKT mutation. AZD5363 may block AKT, which is a protein needed for cancer cell growth. Researchers hope to learn if AZD5363 will shrink this type of cancer or stop its growth.
Detailed description
PRIMARY OBJECTIVE: I. To evaluate the proportion of patients with objective response (OR) to targeted study agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma. SECONDARY OBJECTIVES: I. To evaluate the proportion of patients alive and progression free at 6 months of treatment with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple myeloma. II. To evaluate time until death or disease progression. III. To identify potential predictive biomarkers beyond the genomic alteration by which treatment is assigned or resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and imaging-based assessment platforms. IV. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes from pre- through post-therapy imaging can predict objective response and progression free survival and to evaluate the association between pre-treatment radiomic phenotypes and targeted gene mutation patterns of tumor biopsy specimens. OUTLINE: Patients receive capivasertib (AZD5363) orally (PO) twice daily (BID) on days 1-4, 8-11, 15-18, and 22-25. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months if less than 2 years from study entry, and then every 6 months for year 3 from study entry.
Interventions
DRUGCapivasertib
Given PO
Sponsors
National Cancer Institute (NCI)
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 must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol * Patients must have an AKT mutation as determined via the MATCH Master Protocol * Patients with hormone receptor positive, defined as estrogen receptor and/or progesterone receptor \> 1% by immunohistochemistry, AND HER2 negative unresectable breast cancer, with no overexpression by immunohistochemistry (IHC) or amplification by in-situ hybridization, are allowed to continue fulvestrant or an aromatase inhibitor (anastrozole, letrozole, exemestane) with AZD5363 if patient just progressed on this anti-estrogen therapy. Gonadotrophin releasing hormone (GnRH) agonists (such as leuprolide or goserelin) are allowed. For instance, if the last treatment was letrozole plus goserelin, the patient is allowed to continue the letrozole plus goserelin with AZD5363 * NOTE: Selective estrogen receptor modulators (SERMs), such as tamoxifen or toremifene, are not allowed, given concerns about CYPD26 and CYP3A4 metabolism, respectively * Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have no clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block) * Patients with diabetes or risk for hyperglycemia are eligible. Patients with diabetes mellitus may enter the study unless any of the following
Exclusion criteria
are fulfilled: * Baseline fasting glucose value of \> 8.9 mmol/L or 160 mg/dL (fasting is defined as no calorific intake for at least 8 hours) * Insulin required for routine diabetic management and control * More than two oral hypoglycemic medications required for routine diabetic management and control
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | Tumor assessments occurred at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration | Overall response rate was defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) among all eligible and treated patients. Best overall response was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. The 90% two-sided binomial exact confidence interval was calculated for ORR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 6-month Progression-free Survival (PFS) Rate | Assessed at baseline, then every 2 cycles for the first 26 cycles, and every 3 cycles thereafter until disease progression, up to 3 years post registration, from which 6-month PFS rate is determined | Progression free survival is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. 6 month PFS rate was estimated using the Kaplan-Meier method, which can provide a point estimate for any specific time point. |
| Progression Free Survival (PFS) | Assessed at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration | PFS was defined as time from treatment start date to date of disease progression or death from any causes, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORKevin M Kalinsky
ECOG-ACRIN Cancer Research Group
Participant flow
Recruitment details
Subprotocol Y was activated on May 31, 2016. A total of 43 patients were assigned to this arm after screening, 42 from screening cohort and 1 from outside assay. Of the 43 patients, 35 patients were enrolled to arm Y between July 13, 2016 and August 10, 2017.
Pre-assignment details
To be assigned to a specific MATCH subprotocol, patients needed to submit a tumor biopsy for molecular characterization and those with molecular variants addressed by treatments included in the trial entered corresponding MATCH subprotocol. For the subprotocol Y, patients had to have an AKT mutation.
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Capivasertib) Patients receive capivasertib PO BID on days 1-4, 8-11, 15-18, and 22-25. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Capivasertib: Given PO | 35 |
| Total | 35 |
Baseline characteristics
| Characteristic | Treatment (Capivasertib) |
|---|---|
| Age, Continuous | 61 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 27 Participants |
| Sex: Female, Male Female | 30 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 23 / 35 |
| other Total, other adverse events | 29 / 35 |
| serious Total, serious adverse events | 20 / 35 |
Outcome results
Primary
Overall Response Rate (ORR)
Overall response rate was defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) among all eligible and treated patients. Best overall response was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. The 90% two-sided binomial exact confidence interval was calculated for ORR.
Time frame: Tumor assessments occurred at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration
Population: Patients who were eligible and received protocol treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Capivasertib) | Overall Response Rate (ORR) | 28.6 percentage of participants |
Secondary
6-month Progression-free Survival (PFS) Rate
Progression free survival is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. 6 month PFS rate was estimated using the Kaplan-Meier method, which can provide a point estimate for any specific time point.
Time frame: Assessed at baseline, then every 2 cycles for the first 26 cycles, and every 3 cycles thereafter until disease progression, up to 3 years post registration, from which 6-month PFS rate is determined
Population: Patients who were eligible and received protocol treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Capivasertib) | 6-month Progression-free Survival (PFS) Rate | 50 percentage of participants |
Secondary
Progression Free Survival (PFS)
PFS was defined as time from treatment start date to date of disease progression or death from any causes, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients.
Time frame: Assessed at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration
Population: Patients who were eligible and received protocol treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Capivasertib) | Progression Free Survival (PFS) | 5.5 months |