Trial Outcomes & Findings for Study to Evaluate the Efficacy and Safety of Sirolimus in Subjects With Metastatic, Mismatch Repair Deficient Solid Tumors After Immunotherapy (NCT NCT04393454)
NCT ID: NCT04393454
Last Updated: 2024-07-25
Results Overview
To evaluate the efficacy of sirolimus in patients with metastatic mismatch repair deficient (dMMR) solid cancer after immunotherapy (either due to disease progression or to inability to tolerate treatment), ORR will be determined. For this study ORR will be defined as the percentage of patients who achieve either a complete response (CR = disappearance of all target tumors); or a partial response (PR = ≥30% decrease in the sum of the longest diameters of target tumors) based on Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1) following review of imaging (CT-CAP or PET-CT) data.
TERMINATED
PHASE2
6 participants
Up to approximately 24 weeks after achieving therapeutic sirolimus levels, up to 7 months total
2024-07-25
Participant Flow
Patients were enrolled into the study from 11/16/2020 through 12/22/2021 at the Montefiore-Einstein Cancer Center.
Participant milestones
| Measure |
Sirolimus
Participants will be instructed to take 2 mg every day for 28 days (1 cycle). They will be evaluated in the oncology clinic every 2 weeks to make sure they are tolerating the medication well.
Sirolimus 2 milligram (mg) tablet: Sirolimus (oral) will be started at 2 mg daily. Sirolimus dosing will be titrated to meet serum trough levels of \>8 ng/ml, assayed at 7 days after starting a new dose, by chromatography/mass spectrometry. Once adequate serum levels are met (≥8 ng/ml), the same dosing will be continued until progression of disease as evidenced by imaging, or unacceptable toxicity.
|
|---|---|
|
Overall Study
STARTED
|
6
|
|
Overall Study
COMPLETED
|
4
|
|
Overall Study
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
Sirolimus
Participants will be instructed to take 2 mg every day for 28 days (1 cycle). They will be evaluated in the oncology clinic every 2 weeks to make sure they are tolerating the medication well.
Sirolimus 2 milligram (mg) tablet: Sirolimus (oral) will be started at 2 mg daily. Sirolimus dosing will be titrated to meet serum trough levels of \>8 ng/ml, assayed at 7 days after starting a new dose, by chromatography/mass spectrometry. Once adequate serum levels are met (≥8 ng/ml), the same dosing will be continued until progression of disease as evidenced by imaging, or unacceptable toxicity.
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|---|---|
|
Overall Study
Death
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
Baseline Characteristics
Study to Evaluate the Efficacy and Safety of Sirolimus in Subjects With Metastatic, Mismatch Repair Deficient Solid Tumors After Immunotherapy
Baseline characteristics by cohort
| Measure |
Sirolimus
n=6 Participants
Participants will be instructed to take 2 mg every day for 28 days (1 cycle). They will be evaluated in the oncology clinic every 2 weeks to make sure they are tolerating the medication well.
Sirolimus 2 milligram (mg) Tablet: Sirolimus (oral) will be started at 2 mg daily. Sirolimus dosing will be titrated to meet serum trough levels of \>8 ng/ml, assayed at 7 days after starting a new dose, by chromatography/mass spectrometry. Once adequate serum levels are met (≥8 ng/ml), the same dosing will be continued until progression of disease as evidenced by imaging, or unacceptable toxicity.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
5 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
3 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
6 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to approximately 24 weeks after achieving therapeutic sirolimus levels, up to 7 months totalPopulation: One patient had Stable Disease (SD), but was unable to be analyzed for ORR due to being clinical 'Progression of Disease' (POD) on study. Patient stopped study treatment due to toxicity. As such, only 5 patients were able to evaluated for ORR.
To evaluate the efficacy of sirolimus in patients with metastatic mismatch repair deficient (dMMR) solid cancer after immunotherapy (either due to disease progression or to inability to tolerate treatment), ORR will be determined. For this study ORR will be defined as the percentage of patients who achieve either a complete response (CR = disappearance of all target tumors); or a partial response (PR = ≥30% decrease in the sum of the longest diameters of target tumors) based on Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1) following review of imaging (CT-CAP or PET-CT) data.
Outcome measures
| Measure |
Sirolimus
n=5 Participants
Participants will be instructed to take 2 mg every day for 28 days (1 cycle). They will be evaluated in the oncology clinic every 2 weeks to make sure they are tolerating the medication well.
Sirolimus 2 milligram (mg) Tablet: Sirolimus (oral) will be started at 2 mg daily. Sirolimus dosing will be titrated to meet serum trough levels of \>8 ng/ml, assayed at 7 days after starting a new dose, by chromatography/mass spectrometry. Once adequate serum levels are met (≥8 ng/ml), the same dosing will be continued until progression of disease as evidenced by imaging, or unacceptable toxicity.
|
|---|---|
|
Objective Response Rate (ORR)
|
1 Participants
|
SECONDARY outcome
Timeframe: Approximately 24 weeks after sirolimus initiation, up to approximately 7 months totalPopulation: Progression-free Survival (PFS) was unable to be assessed in 2 of the enrolled patients.
PFS, the duration of time from treatment initiation to progression of known metastases or new metastatic site, or death from any cause after a timeframe of 24 weeks, will be determined following treatment with sirolimus in patients with metastatic mismatch repair deficient (dMMR) solid cancer after immunotherapy (either due to disease progression or to inability to tolerate treatment). Group median number of months will be reported.
Outcome measures
| Measure |
Sirolimus
n=4 Participants
Participants will be instructed to take 2 mg every day for 28 days (1 cycle). They will be evaluated in the oncology clinic every 2 weeks to make sure they are tolerating the medication well.
Sirolimus 2 milligram (mg) Tablet: Sirolimus (oral) will be started at 2 mg daily. Sirolimus dosing will be titrated to meet serum trough levels of \>8 ng/ml, assayed at 7 days after starting a new dose, by chromatography/mass spectrometry. Once adequate serum levels are met (≥8 ng/ml), the same dosing will be continued until progression of disease as evidenced by imaging, or unacceptable toxicity.
|
|---|---|
|
Progression Free Survival (PFS)
|
3.5 months
Interval 3.3 to 6.0
|
SECONDARY outcome
Timeframe: Up to ~24 weeks from the time of tumor response, up to 7 months totalPopulation: Response duration was only able to be evaluated in the one patient who showed a Partial Response
RD, defined as the duration of time from documentation of tumor response until the time of disease progression will be determined following treatment with sirolimus in patients with metastatic mismatch repair deficient (dMMR) solid cancer after immunotherapy (either due to disease progression or to inability to tolerate treatment). Group median number of months will be reported.
Outcome measures
| Measure |
Sirolimus
n=1 Participants
Participants will be instructed to take 2 mg every day for 28 days (1 cycle). They will be evaluated in the oncology clinic every 2 weeks to make sure they are tolerating the medication well.
Sirolimus 2 milligram (mg) Tablet: Sirolimus (oral) will be started at 2 mg daily. Sirolimus dosing will be titrated to meet serum trough levels of \>8 ng/ml, assayed at 7 days after starting a new dose, by chromatography/mass spectrometry. Once adequate serum levels are met (≥8 ng/ml), the same dosing will be continued until progression of disease as evidenced by imaging, or unacceptable toxicity.
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|---|---|
|
Response Duration (RD)
|
6.0 months
Interval 6.0 to 6.0
|
SECONDARY outcome
Timeframe: Approximately 24 weeks after sirolimus initiation, up to approximately 7 months totalPopulation: 2 patients were unable to be evaluated for OS.
Overall Survival, the duration of time from the start of treatment initiation for patients diagnosed with metastatic mismatch repair deficient (dMMR) solid cancer after immunotherapy (either due to disease progression or inability to tolerate treatment) to death from any cause, will be determined. Group median number of months will be reported.
Outcome measures
| Measure |
Sirolimus
n=4 Participants
Participants will be instructed to take 2 mg every day for 28 days (1 cycle). They will be evaluated in the oncology clinic every 2 weeks to make sure they are tolerating the medication well.
Sirolimus 2 milligram (mg) Tablet: Sirolimus (oral) will be started at 2 mg daily. Sirolimus dosing will be titrated to meet serum trough levels of \>8 ng/ml, assayed at 7 days after starting a new dose, by chromatography/mass spectrometry. Once adequate serum levels are met (≥8 ng/ml), the same dosing will be continued until progression of disease as evidenced by imaging, or unacceptable toxicity.
|
|---|---|
|
Overall Survival (OS)
|
6.1 months
Interval 3.7 to 6.9
|
POST_HOC outcome
Timeframe: Up to approximately 24 weeks after achieving therapeutic sirolimus levels, up to 7 months totalTo evaluate the efficacy of sirolimus in patients with metastatic mismatch repair deficient (dMMR) solid cancer after immunotherapy (either due to disease progression or to inability to tolerate treatment), the best OR will be determined based on RECIST criteria following review of imaging (CT-CAP or PET-CT) data. Tumor responses will be categorized based on RECIST v1.1 criteria as follows: Complete Response (CR): disappearance of all target tumors Partial Response (PR): ≥30% decrease in the sum of the longest diameters of target tumors Progressive Disease (PD): at least 20% increase in sum of diameters of target tumor (noting smallest sum on study); absolute increase of 5mm must be demonstrated Stable Disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD Inevaluable/Not Evaluable (NE): No imaging taken/no measurement performed
Outcome measures
| Measure |
Sirolimus
n=6 Participants
Participants will be instructed to take 2 mg every day for 28 days (1 cycle). They will be evaluated in the oncology clinic every 2 weeks to make sure they are tolerating the medication well.
Sirolimus 2 milligram (mg) Tablet: Sirolimus (oral) will be started at 2 mg daily. Sirolimus dosing will be titrated to meet serum trough levels of \>8 ng/ml, assayed at 7 days after starting a new dose, by chromatography/mass spectrometry. Once adequate serum levels are met (≥8 ng/ml), the same dosing will be continued until progression of disease as evidenced by imaging, or unacceptable toxicity.
|
|---|---|
|
Best Overall Response (OR)
CR
|
0 Participants
|
|
Best Overall Response (OR)
PR
|
1 Participants
|
|
Best Overall Response (OR)
SD
|
3 Participants
|
|
Best Overall Response (OR)
PD
|
1 Participants
|
|
Best Overall Response (OR)
NE
|
1 Participants
|
Adverse Events
Sirolimus
Serious adverse events
| Measure |
Sirolimus
n=6 participants at risk
Participants will be instructed to take 2 mg every day for 28 days (1 cycle). They will be evaluated in the oncology clinic every 2 weeks to make sure they are tolerating the medication well.
Sirolimus 2 milligram (mg) Tablet: Sirolimus (oral) will be started at 2 mg daily. Sirolimus dosing will be titrated to meet serum trough levels of \>8 ng/ml, assayed at 7 days after starting a new dose, by chromatography/mass spectrometry. Once adequate serum levels are met (≥8 ng/ml), the same dosing will be continued until progression of disease as evidenced by imaging, or unacceptable toxicity.
|
|---|---|
|
Gastrointestinal disorders
Abdominal Pain
|
16.7%
1/6 • Approximately 24 weeks following initiation of treatment, up to 7 months total.
|
|
Gastrointestinal disorders
Vomiting
|
16.7%
1/6 • Approximately 24 weeks following initiation of treatment, up to 7 months total.
|
Other adverse events
| Measure |
Sirolimus
n=6 participants at risk
Participants will be instructed to take 2 mg every day for 28 days (1 cycle). They will be evaluated in the oncology clinic every 2 weeks to make sure they are tolerating the medication well.
Sirolimus 2 milligram (mg) Tablet: Sirolimus (oral) will be started at 2 mg daily. Sirolimus dosing will be titrated to meet serum trough levels of \>8 ng/ml, assayed at 7 days after starting a new dose, by chromatography/mass spectrometry. Once adequate serum levels are met (≥8 ng/ml), the same dosing will be continued until progression of disease as evidenced by imaging, or unacceptable toxicity.
|
|---|---|
|
General disorders
Fatigue
|
50.0%
3/6 • Approximately 24 weeks following initiation of treatment, up to 7 months total.
|
|
Respiratory, thoracic and mediastinal disorders
Hoarseness
|
16.7%
1/6 • Approximately 24 weeks following initiation of treatment, up to 7 months total.
|
|
Metabolism and nutrition disorders
Anorexia
|
33.3%
2/6 • Approximately 24 weeks following initiation of treatment, up to 7 months total.
|
|
Nervous system disorders
Neuropathy
|
16.7%
1/6 • Approximately 24 weeks following initiation of treatment, up to 7 months total.
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
50.0%
3/6 • Approximately 24 weeks following initiation of treatment, up to 7 months total.
|
|
Gastrointestinal disorders
Abdominal Pain
|
16.7%
1/6 • Approximately 24 weeks following initiation of treatment, up to 7 months total.
|
|
Renal and urinary disorders
Dysuria
|
16.7%
1/6 • Approximately 24 weeks following initiation of treatment, up to 7 months total.
|
|
Gastrointestinal disorders
Diarrhea
|
50.0%
3/6 • Approximately 24 weeks following initiation of treatment, up to 7 months total.
|
|
Cardiac disorders
Hypertension
|
16.7%
1/6 • Approximately 24 weeks following initiation of treatment, up to 7 months total.
|
|
Skin and subcutaneous tissue disorders
Rash Maculo-papular
|
33.3%
2/6 • Approximately 24 weeks following initiation of treatment, up to 7 months total.
|
|
Gastrointestinal disorders
Mucositis, Oral
|
16.7%
1/6 • Approximately 24 weeks following initiation of treatment, up to 7 months total.
|
|
Renal and urinary disorders
Acute Kidney Injury
|
16.7%
1/6 • Approximately 24 weeks following initiation of treatment, up to 7 months total.
|
|
Nervous system disorders
Headaches
|
16.7%
1/6 • Approximately 24 weeks following initiation of treatment, up to 7 months total.
|
|
Investigations
Weight Loss
|
16.7%
1/6 • Approximately 24 weeks following initiation of treatment, up to 7 months total.
|
|
Musculoskeletal and connective tissue disorders
Pain
|
16.7%
1/6 • Approximately 24 weeks following initiation of treatment, up to 7 months total.
|
|
General disorders
Edema Limbs
|
33.3%
2/6 • Approximately 24 weeks following initiation of treatment, up to 7 months total.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
16.7%
1/6 • Approximately 24 weeks following initiation of treatment, up to 7 months total.
|
|
Metabolism and nutrition disorders
Hypokalemia
|
16.7%
1/6 • Approximately 24 weeks following initiation of treatment, up to 7 months total.
|
|
Infections and infestations
Urinary Tract Infection
|
16.7%
1/6 • Approximately 24 weeks following initiation of treatment, up to 7 months total.
|
|
Infections and infestations
COVID Infection
|
16.7%
1/6 • Approximately 24 weeks following initiation of treatment, up to 7 months total.
|
|
Blood and lymphatic system disorders
Anemia
|
33.3%
2/6 • Approximately 24 weeks following initiation of treatment, up to 7 months total.
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
16.7%
1/6 • Approximately 24 weeks following initiation of treatment, up to 7 months total.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place