Trial Outcomes & Findings for Bortezomib and Pemetrexed Disodium in Treating Patients With Advanced Non-Small Cell Lung Cancer or Other Solid Tumors (NCT NCT00389805)
NCT ID: NCT00389805
Last Updated: 2018-10-31
Results Overview
Grade 4 thrombocytopenia or grade 3 thrombocytopenia associated with bleeding, requirement for transfusion or lasting \>7 days; febrile neutropenia; grade 3 neutropenia associated with infection; any other grade \>/=3 non-hematologic toxicity considered by the investigator to be related to study drug.
COMPLETED
PHASE1/PHASE2
27 participants
Up to 36 months
2018-10-31
Participant Flow
Participant milestones
| Measure |
Arm A
Pemetrexed on day 1 (500 -600 mg/m2 IV) and bortezomib twice weekly (0.7-1.3mg/m3) on days 1, 4, 8, and 11 every 21 days
|
Arm B
Pemetrexed on day 1 (500 -600 mg/m2 IV) and bortezomib twice weekly (0.7-1.3mg/m2) on days 1 and 8 every 21 days
|
|---|---|---|
|
Phase I
STARTED
|
15
|
12
|
|
Phase I
COMPLETED
|
15
|
12
|
|
Phase I
NOT COMPLETED
|
0
|
0
|
|
Phase II
STARTED
|
0
|
0
|
|
Phase II
COMPLETED
|
0
|
0
|
|
Phase II
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Bortezomib and Pemetrexed Disodium in Treating Patients With Advanced Non-Small Cell Lung Cancer or Other Solid Tumors
Baseline characteristics by cohort
| Measure |
Arm A
n=15 Participants
Pemetrexed on day 1 and bortezomib days 1, 4, 8, and 11 every 21 days
|
Arm B
n=12 Participants
Pemetrexed on day 1 and bortezomib days 1 and 8 every 21 days
|
Total
n=27 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
62 years
n=5 Participants
|
59 years
n=7 Participants
|
60 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
15 participants
n=5 Participants
|
12 participants
n=7 Participants
|
27 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 36 monthsGrade 4 thrombocytopenia or grade 3 thrombocytopenia associated with bleeding, requirement for transfusion or lasting \>7 days; febrile neutropenia; grade 3 neutropenia associated with infection; any other grade \>/=3 non-hematologic toxicity considered by the investigator to be related to study drug.
Outcome measures
| Measure |
Arm A
n=15 Participants
Pemetrexed on day 1 and bortezomib days 1, 4, 8, and 11 every 21 days
|
Arm B
n=12 Participants
Pemetrexed on day 1 and bortezomib days 1 and 8 every 21 days
|
|---|---|---|
|
Number of Patients Experiencing a Dose-limiting Toxicity (Phase I)
|
3 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Throughout the entire study (up to 36 months).Number of participants with treatment-related adverse events as assessed by CTCAE v3.0 (Phase I).
Outcome measures
| Measure |
Arm A
n=15 Participants
Pemetrexed on day 1 and bortezomib days 1, 4, 8, and 11 every 21 days
|
Arm B
n=12 Participants
Pemetrexed on day 1 and bortezomib days 1 and 8 every 21 days
|
|---|---|---|
|
Number of Participants Who Experience Adverse Events (Phase I)
|
15 Participants
|
12 Participants
|
PRIMARY outcome
Timeframe: First cycle of treatment (3 weeks)Grade 3/4 toxicity occurring in a patient within 1 cycle.
Outcome measures
| Measure |
Arm A
n=15 Participants
Pemetrexed on day 1 and bortezomib days 1, 4, 8, and 11 every 21 days
|
Arm B
n=12 Participants
Pemetrexed on day 1 and bortezomib days 1 and 8 every 21 days
|
|---|---|---|
|
Number of Patients With Grade ≥ 3 Toxicity (Phase I)
Neutropenia
|
12 participants
|
1 participants
|
|
Number of Patients With Grade ≥ 3 Toxicity (Phase I)
Anemia
|
1 participants
|
0 participants
|
|
Number of Patients With Grade ≥ 3 Toxicity (Phase I)
Thrombocytopenia
|
0 participants
|
1 participants
|
|
Number of Patients With Grade ≥ 3 Toxicity (Phase I)
Increased transaminases
|
1 participants
|
0 participants
|
|
Number of Patients With Grade ≥ 3 Toxicity (Phase I)
Fatigue
|
2 participants
|
0 participants
|
PRIMARY outcome
Timeframe: From start of treatment until disease progression/recurrence.Population: The Phase II study was not conducted.
To determine the response rate of bortezomib in combination with pemetrexed in patients with advanced NSCLC. Response rate was assessed by CT scan. CT scans was performed at baseline and every two cycles (prior to 3rd and 5th cycle). The evaluation of response was based on standard RECIST criteria.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 36 monthsAdverse events possibly related to treatment, graded according to the NCI CTCAE v3.0.
Outcome measures
| Measure |
Arm A
n=15 Participants
Pemetrexed on day 1 and bortezomib days 1, 4, 8, and 11 every 21 days
|
Arm B
n=12 Participants
Pemetrexed on day 1 and bortezomib days 1 and 8 every 21 days
|
|---|---|---|
|
Number of Patients With Toxicity by NCI CTC v3.0 (Phase I)
Weakness
|
0 participants
|
2 participants
|
|
Number of Patients With Toxicity by NCI CTC v3.0 (Phase I)
Neutropenia
|
12 participants
|
1 participants
|
|
Number of Patients With Toxicity by NCI CTC v3.0 (Phase I)
Anemia
|
1 participants
|
0 participants
|
|
Number of Patients With Toxicity by NCI CTC v3.0 (Phase I)
Thrombocytopenia
|
0 participants
|
1 participants
|
|
Number of Patients With Toxicity by NCI CTC v3.0 (Phase I)
Increased transaminases
|
12 participants
|
5 participants
|
|
Number of Patients With Toxicity by NCI CTC v3.0 (Phase I)
Anorexia
|
4 participants
|
6 participants
|
|
Number of Patients With Toxicity by NCI CTC v3.0 (Phase I)
Constipation
|
5 participants
|
3 participants
|
|
Number of Patients With Toxicity by NCI CTC v3.0 (Phase I)
Cough
|
5 participants
|
4 participants
|
|
Number of Patients With Toxicity by NCI CTC v3.0 (Phase I)
Dehydration
|
4 participants
|
1 participants
|
|
Number of Patients With Toxicity by NCI CTC v3.0 (Phase I)
Diarrhea
|
2 participants
|
3 participants
|
|
Number of Patients With Toxicity by NCI CTC v3.0 (Phase I)
Dizziness
|
5 participants
|
4 participants
|
|
Number of Patients With Toxicity by NCI CTC v3.0 (Phase I)
Edema
|
4 participants
|
4 participants
|
|
Number of Patients With Toxicity by NCI CTC v3.0 (Phase I)
Fatigue
|
15 participants
|
11 participants
|
|
Number of Patients With Toxicity by NCI CTC v3.0 (Phase I)
Fever
|
3 participants
|
3 participants
|
|
Number of Patients With Toxicity by NCI CTC v3.0 (Phase I)
Infection
|
6 participants
|
4 participants
|
|
Number of Patients With Toxicity by NCI CTC v3.0 (Phase I)
Nausea +/- vomiting
|
10 participants
|
6 participants
|
|
Number of Patients With Toxicity by NCI CTC v3.0 (Phase I)
Neuropathy
|
4 participants
|
6 participants
|
|
Number of Patients With Toxicity by NCI CTC v3.0 (Phase I)
Rash
|
6 participants
|
5 participants
|
|
Number of Patients With Toxicity by NCI CTC v3.0 (Phase I)
Renal impairment
|
5 participants
|
1 participants
|
SECONDARY outcome
Timeframe: Up to 36 monthsOutcome measures
| Measure |
Arm A
n=15 Participants
Pemetrexed on day 1 and bortezomib days 1, 4, 8, and 11 every 21 days
|
Arm B
n=12 Participants
Pemetrexed on day 1 and bortezomib days 1 and 8 every 21 days
|
|---|---|---|
|
Maximum Tolerated Dose of Bortezomib in Combination With Pemetrexel (Phase I)
|
1.3 Mg/m^2
|
1.6 Mg/m^2
|
SECONDARY outcome
Timeframe: Up to 36 monthsPopulation: All patients for whom response evaluation measurements were recorded at baseline and after 2 cycles.
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) for target lesions and assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Best overall response is the best response recorded from the start of the treatment until disease progression/recurrence.
Outcome measures
| Measure |
Arm A
n=15 Participants
Pemetrexed on day 1 and bortezomib days 1, 4, 8, and 11 every 21 days
|
Arm B
n=12 Participants
Pemetrexed on day 1 and bortezomib days 1 and 8 every 21 days
|
|---|---|---|
|
Number of Participants With Response to Therapy as Measured by RECIST (Phase I)
Stable Disease (SD)
|
7 Participants
|
6 Participants
|
|
Number of Participants With Response to Therapy as Measured by RECIST (Phase I)
Complete Response (CR)
|
0 Participants
|
0 Participants
|
|
Number of Participants With Response to Therapy as Measured by RECIST (Phase I)
Partial Response (PR)
|
1 Participants
|
1 Participants
|
|
Number of Participants With Response to Therapy as Measured by RECIST (Phase I)
Progressive Disease (PD)
|
7 Participants
|
5 Participants
|
SECONDARY outcome
Timeframe: Up to 36 monthsPopulation: The Phase II study was not conducted.
Each adverse event will be determined by using the NCI CTCAE, Version 3.0.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 36 monthsPopulation: The Phase II study was not conducted.
Expression of relevant molecular targets of the proteasome, which is inhibited by bortezomib.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 36 monthsPopulation: The Phase II study was not conducted.
Overexpression of reduced folate carrier (RFC) protein is thought to contribute to decreased resistance to pemetrexed. Levels of expression will be studied by measuring mRNA transcripts using quantitative Reverse Transcriptase-Polymerase Chain Reaction in archival patient tumor specimens.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 36 monthsPopulation: The Phase II study was not conducted.
Tumor levels of BCL-2, BCL-xL and BAX will be assessed by immunohistochemistry (IHC).
Outcome measures
Outcome data not reported
Adverse Events
Arm A
Arm B
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Arm A
n=15 participants at risk
Pemetrexed on day 1 and bortezomib days 1, 4, 8, and 11 every 21 days
|
Arm B
n=12 participants at risk
Pemetrexed on day 1 and bortezomib days 1 and 8 every 21 days
|
|---|---|---|
|
Hepatobiliary disorders
Increased transaminases
|
80.0%
12/15
|
41.7%
5/12
|
|
Metabolism and nutrition disorders
Anorexia
|
26.7%
4/15
|
50.0%
6/12
|
|
Gastrointestinal disorders
Constipation
|
33.3%
5/15
|
25.0%
3/12
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
33.3%
5/15
|
33.3%
4/12
|
|
Metabolism and nutrition disorders
Dehydration
|
26.7%
4/15
|
8.3%
1/12
|
|
Gastrointestinal disorders
Diarrhea
|
13.3%
2/15
|
25.0%
3/12
|
|
Nervous system disorders
Dizziness
|
33.3%
5/15
|
33.3%
4/12
|
|
General disorders
Edema
|
26.7%
4/15
|
33.3%
4/12
|
|
General disorders
Fatigue
|
100.0%
15/15
|
91.7%
11/12
|
|
General disorders
Fever
|
20.0%
3/15
|
25.0%
3/12
|
|
Infections and infestations
Infection
|
40.0%
6/15
|
33.3%
4/12
|
|
Gastrointestinal disorders
Nausea +/- vomiting
|
66.7%
10/15
|
50.0%
6/12
|
|
Nervous system disorders
Neuropathy
|
26.7%
4/15
|
50.0%
6/12
|
|
Skin and subcutaneous tissue disorders
Rash
|
40.0%
6/15
|
41.7%
5/12
|
|
Renal and urinary disorders
Renal impairment
|
33.3%
5/15
|
8.3%
1/12
|
|
Musculoskeletal and connective tissue disorders
Weakness
|
0.00%
0/15
|
16.7%
2/12
|
|
Blood and lymphatic system disorders
Neutropenia
|
80.0%
12/15
|
8.3%
1/12
|
|
Blood and lymphatic system disorders
Anemia
|
6.7%
1/15
|
0.00%
0/12
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/15
|
8.3%
1/12
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place