Trial Outcomes & Findings for Everolimus and OSI-906 for Patients With Refractory Metastatic Colorectal Cancer (NCT NCT01154335)

Last Updated: 2022-05-03

Results Overview

The MTD of the drug combination will be determined as the highest dose at which ≤1 of 6 subjects experiences a Grade 3 or Grade 4 DLT according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

18 participants

Primary outcome timeframe

18 Months

Results posted on

2022-05-03

Participant Flow

Participant milestones

Participant milestones
Measure	Dose Level 1 combination of OSI-906 and everolimus OSI-906: 50 mg Twice a Day, cycle-28 days Everolimus: 5mg Daily, cycle-28 days	Dose Level 2 combination of OSI-906 and everolimus OSI-906: 100 mg Twice a Day, cycle-28 days Everolimus: 10mg Daily, cycle-28 days	Dose Level 2a combination of OSI-906 and everolimus OSI-906: 100 mg Twice a Day, cycle-28 days Everolimus: 5mg Daily, cycle-28 days
Overall Study STARTED	7	6	5
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	7	6	5

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Everolimus and OSI-906 for Patients With Refractory Metastatic Colorectal Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dose Level 1 n=7 Participants combination of OSI-906 and everolimus OSI-906: 50 mg Twice a Day, cycle-28 days Everolimus: 5mg Daily, cycle-28 days	Dose Level 2 n=6 Participants combination of OSI-906 and everolimus OSI-906: 100 mg Twice a Day, cycle-28 days Everolimus: 10mg Daily, cycle-28 days	Dose Level 2a n=5 Participants combination of OSI-906 and everolimus OSI-906: 100 mg Twice a Day, cycle-28 days Everolimus: 5mg Daily, cycle-28 days	Total n=18 Participants Total of all reporting groups
Age, Continuous	55 years n=5 Participants	54 years n=7 Participants	70 years n=5 Participants	55 years n=4 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	4 Participants n=7 Participants	1 Participants n=5 Participants	9 Participants n=4 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	9 Participants n=4 Participants
Region of Enrollment United States	7 participants n=5 Participants	6 participants n=7 Participants	5 participants n=5 Participants	18 participants n=4 Participants

PRIMARY outcome

Timeframe: 18 Months

Outcome measures

Outcome measures
Measure	All Patients n=18 Participants Determination of the MTD consists of the selection of one of the three dose levels as the maximum tolerated dose. This outcome is the same for all patients.	Dose Level 2 combination of OSI-906 (100 mg Twice a Day, cycle-28 days) and everolimus (10 mg Daily, cycle-28 days)	Dose Level 2a combination of OSI-906 (100 mg Twice a Day, cycle-28 days) and everolimus (5 mg Daily, cycle-28 days)
To Determine the Maximum Tolerated Dose (MTD) of the Combination of OSI-906 and Everolimus for the Treatment of Patients With Refractory Metastatic Colorectal Cancer. OSI-906 BID Dose	50 milligrams	—	—
To Determine the Maximum Tolerated Dose (MTD) of the Combination of OSI-906 and Everolimus for the Treatment of Patients With Refractory Metastatic Colorectal Cancer. Everolimus QD Dose	5 milligrams	—	—

SECONDARY outcome

Timeframe: 18 Months

Progression-free survival (PFS) is defined as the time between Day 1 Cycle 1 and date of first documented recurrence or death. Patients who do not exhibit progression while on trial will be censored at their last known assessment. Progression is defined per RECIST criteria as either 1) at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest (nadir) sum since the treatment started, or the appearance of one or more new lesions. Requires not only 20% increase, but absolute increase of a minimum of 5 mm over sum. OR 2) Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

Outcome measures

Outcome measures
Measure	All Patients n=7 Participants Determination of the MTD consists of the selection of one of the three dose levels as the maximum tolerated dose. This outcome is the same for all patients.	Dose Level 2 n=6 Participants combination of OSI-906 (100 mg Twice a Day, cycle-28 days) and everolimus (10 mg Daily, cycle-28 days)	Dose Level 2a n=5 Participants combination of OSI-906 (100 mg Twice a Day, cycle-28 days) and everolimus (5 mg Daily, cycle-28 days)
Progression-Free Survival (PFS)	2.8 months Standard Deviation 1	3.6 months Standard Deviation 5.2	1.6 months Standard Deviation 0.5

SECONDARY outcome

Timeframe: 18 months

Overall survival (OS) is defined as the time between Day 1 Cycle 1 to the date of death from any cause. Those remaining alive will be censored at their last known assessment or follow-up.

Outcome measures

Outcome measures
Measure	All Patients n=7 Participants Determination of the MTD consists of the selection of one of the three dose levels as the maximum tolerated dose. This outcome is the same for all patients.	Dose Level 2 n=6 Participants combination of OSI-906 (100 mg Twice a Day, cycle-28 days) and everolimus (10 mg Daily, cycle-28 days)	Dose Level 2a n=5 Participants combination of OSI-906 (100 mg Twice a Day, cycle-28 days) and everolimus (5 mg Daily, cycle-28 days)
Overall Survival (OS)	5.1 weeks Standard Deviation 2.4	5.1 weeks Standard Deviation 5	3.3 weeks Standard Deviation 2.4

SECONDARY outcome

Timeframe: 18 months

Population: Only patients who received at least 8 weeks of treatment were considered evaluable for response and were included in the response rate analysis

Response rate (RR) will be estimated as the proportion of patients exhibiting complete response or partial response out of all evaluable cases. Complete Response is defined per RECIST as disappearance of all target/non-target lesions and normalization of tumor markers. Partial Response is defined per RECIST as At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.

Outcome measures

Outcome measures
Measure	All Patients n=6 Participants Determination of the MTD consists of the selection of one of the three dose levels as the maximum tolerated dose. This outcome is the same for all patients.	Dose Level 2 n=1 Participants combination of OSI-906 (100 mg Twice a Day, cycle-28 days) and everolimus (10 mg Daily, cycle-28 days)	Dose Level 2a n=3 Participants combination of OSI-906 (100 mg Twice a Day, cycle-28 days) and everolimus (5 mg Daily, cycle-28 days)
Response Rate	0 Participants	0 Participants	0 Participants

Adverse Events

Dose Level 1

Serious events: 2 serious events

Other events: 7 other events

Deaths: 0 deaths

Dose Level 2

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Dose Level 2a

Serious events: 2 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Dose Level 1 n=7 participants at risk combination of OSI-906 (50 mg Twice a Day, cycle-28 days) and everolimus (5 mg Daily, cycle-28 days)	Dose Level 2 n=6 participants at risk combination of OSI-906 (100 mg Twice a Day, cycle-28 days) and everolimus (10 mg Daily, cycle-28 days)	Dose Level 2a n=5 participants at risk combination of OSI-906 (50 mg Twice a Day, cycle-28 days) and everolimus (5 mg Daily, cycle-28 days)
Gastrointestinal disorders Gastrointestinal disorders - Other, esophageal spasm	0.00% 0/7 • 18 months All patients who received at least one dose of protocol treatment were followed for safety. Adverse events and serious adverse events were collected from the day of the first dose to 30 days after the last dose of the study medication and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	0.00% 0/6 • 18 months All patients who received at least one dose of protocol treatment were followed for safety. Adverse events and serious adverse events were collected from the day of the first dose to 30 days after the last dose of the study medication and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	20.0% 1/5 • Number of events 1 • 18 months All patients who received at least one dose of protocol treatment were followed for safety. Adverse events and serious adverse events were collected from the day of the first dose to 30 days after the last dose of the study medication and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Gastrointestinal disorders Gastrointestinal disorders - Other, mechanical bowel obstruction	14.3% 1/7 • Number of events 1 • 18 months All patients who received at least one dose of protocol treatment were followed for safety. Adverse events and serious adverse events were collected from the day of the first dose to 30 days after the last dose of the study medication and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	0.00% 0/6 • 18 months All patients who received at least one dose of protocol treatment were followed for safety. Adverse events and serious adverse events were collected from the day of the first dose to 30 days after the last dose of the study medication and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	0.00% 0/5 • 18 months All patients who received at least one dose of protocol treatment were followed for safety. Adverse events and serious adverse events were collected from the day of the first dose to 30 days after the last dose of the study medication and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
General disorders General disorders and administration site conditions - Other, disease progression	0.00% 0/7 • 18 months All patients who received at least one dose of protocol treatment were followed for safety. Adverse events and serious adverse events were collected from the day of the first dose to 30 days after the last dose of the study medication and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	16.7% 1/6 • Number of events 1 • 18 months All patients who received at least one dose of protocol treatment were followed for safety. Adverse events and serious adverse events were collected from the day of the first dose to 30 days after the last dose of the study medication and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	0.00% 0/5 • 18 months All patients who received at least one dose of protocol treatment were followed for safety. Adverse events and serious adverse events were collected from the day of the first dose to 30 days after the last dose of the study medication and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/7 • 18 months All patients who received at least one dose of protocol treatment were followed for safety. Adverse events and serious adverse events were collected from the day of the first dose to 30 days after the last dose of the study medication and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	0.00% 0/6 • 18 months All patients who received at least one dose of protocol treatment were followed for safety. Adverse events and serious adverse events were collected from the day of the first dose to 30 days after the last dose of the study medication and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	20.0% 1/5 • Number of events 1 • 18 months All patients who received at least one dose of protocol treatment were followed for safety. Adverse events and serious adverse events were collected from the day of the first dose to 30 days after the last dose of the study medication and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Respiratory, thoracic and mediastinal disorders Pleural effusion	14.3% 1/7 • Number of events 1 • 18 months All patients who received at least one dose of protocol treatment were followed for safety. Adverse events and serious adverse events were collected from the day of the first dose to 30 days after the last dose of the study medication and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	0.00% 0/6 • 18 months All patients who received at least one dose of protocol treatment were followed for safety. Adverse events and serious adverse events were collected from the day of the first dose to 30 days after the last dose of the study medication and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	0.00% 0/5 • 18 months All patients who received at least one dose of protocol treatment were followed for safety. Adverse events and serious adverse events were collected from the day of the first dose to 30 days after the last dose of the study medication and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Blood and lymphatic system disorders Thrombocytopenia with Bleeding	0.00% 0/7 • 18 months All patients who received at least one dose of protocol treatment were followed for safety. Adverse events and serious adverse events were collected from the day of the first dose to 30 days after the last dose of the study medication and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	0.00% 0/6 • 18 months All patients who received at least one dose of protocol treatment were followed for safety. Adverse events and serious adverse events were collected from the day of the first dose to 30 days after the last dose of the study medication and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	20.0% 1/5 • Number of events 1 • 18 months All patients who received at least one dose of protocol treatment were followed for safety. Adverse events and serious adverse events were collected from the day of the first dose to 30 days after the last dose of the study medication and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

Other adverse events

Additional Information

John D Hainsworth, MD

Sarah Cannon Research Institute

Phone: 1-877-691-7274

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The sponsor can review/embargo results communications prior to public release for a period that is \>60 but =180 days from date submitted to sponsor, who may require changes to the communication in order to remove specifically identified confidential information (other than study data) and/or delay the proposed publication to enable the sponsor to seek patent protection for inventions. The PI may not publish its results until 18 mos. after the trial has been completed at all sites
Publication restrictions are in place

Restriction type: OTHER