Malignant Solid Neoplasm
Conditions
Brief summary
The phase II MATCH treatment trial tests how well copanlisib works to treat patients with cancer with PTEN loss. Copanlisib may stop the growth of tumor cells and may kill them by blocking some of the enzymes needed for cell 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 copanlisib intravenously (IV) at a dose of 60 mg over 1 hour on day 18 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsy on study and radiologic evaluation and blood sample collection throughout the study. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 1 year. THE MATCH SCREENING TRIAL: Please see NCT02465060 for information on the MATCH Screening Protocol and applicable documents.
Interventions
PROCEDUREBiopsy Procedure
Undergo tumor biopsy
PROCEDUREBiospecimen Collection
Undergo blood sample collection
DRUGCopanlisib
Given IV
PROCEDURERadiologic Examination
Undergo radiologic evaluation
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Patients must have met applicable eligibility criteria in the Master MATCH Protocol EAY131/ NCI-2015-00054 prior to registration to treatment subprotocol * Patients must fulfill all eligibility criteria outlined in Section 3.1 of MATCH Master Protocol (excluding Section 3.1.6) at the time of registration to treatment step (Step 1, 3, 5, 7) * Patients must have complete loss of cytoplasmic and nuclear PTEN by immunohistochemistry (ICH) as determined via the MATCH Master Protocol and described in Appendix I. Patients can have any PTEN mutation or deletion status, but MUST have PTEN loss by IHC * NOTE: For patients entering the study, all patients must have PTEN IHC performed as described in the MATCH Master Protocol. This includes patients entering the study via the outside assay process * Patients must not have co-existing aberrations in the MAPK or PI3K/MTOR pathways as determined by the MATCH screening assessment in NRAS, HRAS, KRAS, BRAF, PIK3CA, AKT or mTOR * 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 must not have known hypersensitivity to copanlisib or compounds of similar chemical or biologic composition * Patients must not have had prior treatment with copanlisib or other PI3K inhibitors, AKT inhibitors or mTOR inhibitors * Patients must not be on strong inhibitors or inducers of CYP3A4 within two weeks prior to start of study treatment and for the duration of study treatment * Patients should stop using herbal medications at least 7 days prior to the first dose of copanlisib. Herbal medications include, but are not limited to: St. John's Wort, Kava, ephedra, gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, black cohosh and ginseng * Patients with type I or II diabetes mellitus must have a hemoglobulin (Hb) A1c ≤ 8.5% within 28 days from registration * Patients must not have uncontrolled hypertension defined as systolic blood pressure (SBP) greater than 160 mmHg or diastolic blood pressure (BP) greater than 100 mmHg or use of more than 2 anti-hypertensive medications * Patients must not have HER2 positive (3+ by IHC or fluorescence in situ hybridization \[FISH\] ratio ≥ 2) breast cancer * Patients must not have indolent NHL (Non-Hodgkin's Lymphoma) or DLBCL (diffuse large B cell lymphoma) because other studies are ongoing with this agent in this group patients * Patients must not be on anti-arrhythmic therapy other than digoxin or beta-blockers * Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9 /L * Platelets ≥ 100x10\^9 /L * Hemoglobulin (Hgb) \> 9 g/dl * Total serum bilirubin \< 2.0 mg/dL * Aspartate aminotransferase (ALT) and Alanine aminotransferase (AST) \< 2.5 x upper limit of normal (ULN) (\< 5 x ULN in patients with liver metastases) * Serum creatinine \< 1.5 x ULN * Patients with non-healing wound, ulcer, or bone fracture are not eligible * Patients with history of or current interstitial pneumonitis are not eligible. NOTE: For solid tumors, CMV PCR can be obtained at the discretion of treating physician or local institutional guidelines * Patients must agree not to conceive or father children by agreeing to use contraception while receiving study treatment and for 1 month after the last dose of copanlisib
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective 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 | ORR is defined as the percentage of patients whose tumors have a complete or partial response to treatment among analyzable patients. Objective response is defined consistent with 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. Details about how to define complete response and partial response can be found in the master protocol. 90% two-sided binomial exact confidence interval is 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. Please refer to the protocol for detailed definitions of disease progression. 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 | 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. Please refer to the protocol for detailed definitions of disease progression. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJordi Rodon Ahnert
M.D. Anderson Cancer Center
Participant flow
Recruitment details
Subprotocol Z1G was activated on June 20, 2018. Twenty-two patients were enrolled between October 2018 and September 2021. All patients were enrolled through the outside laboratory.
Pre-assignment details
The PTEN loss status was determined by a CLIA-approved assay performed in NCI-MATCH approved laboratory for all patients in this arm. Twenty-one out of the 22 outside lab patients had their samples centrally confirmed.
Participants by arm
| Arm | Count |
|---|---|
| Subprotocol Z1G (PTEN Loss) Patients receive copanlisib IV at a dose of 60 mg over 1 hour on day 18 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsy on study and radiologic evaluation and blood sample collection throughout the study. | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Subprotocol Z1G (PTEN Loss) |
|---|---|
| Age, Continuous | 62 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 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 | 1 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 | 16 Participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 16 / 22 |
| other Total, other adverse events | 13 / 22 |
| serious Total, serious adverse events | 7 / 22 |
Outcome results
Primary
Objective Response Rate (ORR)
ORR is defined as the percentage of patients whose tumors have a complete or partial response to treatment among analyzable patients. Objective response is defined consistent with 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. Details about how to define complete response and partial response can be found in the master protocol. 90% two-sided binomial exact confidence interval is 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: Eligible, treated and mutation status confirmed
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Subprotocol Z1G (PTEN Loss) | Objective Response Rate (ORR) | 0 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. Please refer to the protocol for detailed definitions of disease progression. 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: Eligible, treated and mutation status confirmed
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Subprotocol Z1G (PTEN Loss) | 6-month Progression-free Survival (PFS) Rate | 17.5 percentage of participants |
Secondary
Progression Free Survival
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. Please refer to the protocol for detailed definitions of disease progression.
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: Eligible, treated and mutation status confirmed
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Subprotocol Z1G (PTEN Loss) | Progression Free Survival | 1.8 months |