Trial Outcomes & Findings for Hydroxychloroquine With or Without Erlotinib in Advanced Non-small Cell Lung Cancer (NSCLC) (NCT NCT01026844)
NCT ID: NCT01026844
Last Updated: 2017-01-30
Results Overview
HCQ doses tested included 400mg, 600mg, 800mg, and 1000mg. Dose-limiting toxicities (DLTs) were defined as CTC of grade 2 or higher retinopathy or keratitis, or CTC of grade 3 or higher hematologic, skin, CNS, neuropathic, cardiac, respiratory, gastrointestinal, or renal AEs in the first cycle considered at least possibly related to HCQ. If a DLT was observed, an additional three patients were enrolled at that dose level. The maximum tolerated dose for HCQ in each arm would be defined as one dose level below that at which two or more of 6 patients experienced a DLT, or if no DLTs were observed, the highest tested dose.
TERMINATED
PHASE1
27 participants
2 years
2017-01-30
Participant Flow
Twenty-seven patients were enrolled between August 2007 and May 2010. They were all patients at Mass General Hospital Cancer Center
Participant milestones
| Measure |
Erlotinib Plus HCQ (Hydroxychloroquine)
Erlotinib at 150mg QD and HCQ at escalating doses (400mg, 600mg, 800mg and 1000mg QD)
|
HCQ (Hydroxychloroquine)
HCQ at escalating doses (400mg, 600mg, 800mg, and 1000mg QD)
|
|---|---|---|
|
Overall Study
STARTED
|
19
|
8
|
|
Overall Study
COMPLETED
|
19
|
8
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Hydroxychloroquine With or Without Erlotinib in Advanced Non-small Cell Lung Cancer (NSCLC)
Baseline characteristics by cohort
| Measure |
Erlotinib Plus HCQ (Hydroxychloroquine)
n=19 Participants
Erlotinib at 150mg QD and HCQ at escalating doses (400mg, 600mg, 800mg and 1000mg QD)
|
HCQ (Hydroxychloroquine)
n=8 Participants
HCQ at escalating doses (400mg, 600mg, 800mg, and 1000mg QD)
|
Total
n=27 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
9 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
10 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Age, Continuous
|
65 years
n=5 Participants
|
61 years
n=7 Participants
|
64 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
19 participants
n=5 Participants
|
8 participants
n=7 Participants
|
27 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 2 yearsPopulation: In October 2008, after enrollment of 18 patients (8 on arm A and 10 on arm B), the study was amended to limit enrollment to arm B only (HCQ plus erlotinib) given the increasing preclinical evidence supporting a role for combination therapy (but not HCQ monotherapy) and to help increase overall patient accrual.
HCQ doses tested included 400mg, 600mg, 800mg, and 1000mg. Dose-limiting toxicities (DLTs) were defined as CTC of grade 2 or higher retinopathy or keratitis, or CTC of grade 3 or higher hematologic, skin, CNS, neuropathic, cardiac, respiratory, gastrointestinal, or renal AEs in the first cycle considered at least possibly related to HCQ. If a DLT was observed, an additional three patients were enrolled at that dose level. The maximum tolerated dose for HCQ in each arm would be defined as one dose level below that at which two or more of 6 patients experienced a DLT, or if no DLTs were observed, the highest tested dose.
Outcome measures
| Measure |
Erlotinib Plus HCQ (Hydroxychloroquine)
n=19 Participants
Erlotinib at 150mg QD and HCQ at escalating doses (400mg, 600mg, 800mg and 1000mg QD)
|
HCQ (Hydroxychloroquine)
n=8 Participants
HCQ at escalating doses (400mg, 600mg, 800mg, and 1000mg QD)
|
|---|---|---|
|
Describe the Number and Type of Observed Dose Limiting Toxcities
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: The patients participating in the randomized portion of the study were analyzed for PK parameters. When the HCQ alone arm of the study was closed, PK measurements were no longer performed
PK parameter tested was dose normalized minimum steady state concentration (Cmin SS) of HCQ in micromolar per gram. Note this outcome was only analyzed for the first 21 patients enrolled, 13 on erlotinib/HCQ and 8 on HCQ arm.
Outcome measures
| Measure |
Erlotinib Plus HCQ (Hydroxychloroquine)
n=13 Participants
Erlotinib at 150mg QD and HCQ at escalating doses (400mg, 600mg, 800mg and 1000mg QD)
|
HCQ (Hydroxychloroquine)
n=8 Participants
HCQ at escalating doses (400mg, 600mg, 800mg, and 1000mg QD)
|
|---|---|---|
|
Determine the Pharmacokinetic (PK) Parameters of Hydroxychloroquine (HCQ) Plus Erlotinib.
|
5.93 micromolar per gram
Standard Deviation 2.51
|
9.40 micromolar per gram
Standard Deviation 5.85
|
SECONDARY outcome
Timeframe: 2 yearsNumber of Response Evaluation Criteria in Solid Tumors (RECIST) responses divided by number of patients treated. Per RECIST version 1.0 complete response (CR) is defined as disappearance of all target lesions; Partial Response (PR) is defined as \>=30% decrease in the sum of the longest diameter of target lesions. The objective tumor response rate is the CR + PR divided by the total number of patients
Outcome measures
| Measure |
Erlotinib Plus HCQ (Hydroxychloroquine)
n=19 Participants
Erlotinib at 150mg QD and HCQ at escalating doses (400mg, 600mg, 800mg and 1000mg QD)
|
HCQ (Hydroxychloroquine)
n=8 Participants
HCQ at escalating doses (400mg, 600mg, 800mg, and 1000mg QD)
|
|---|---|---|
|
Objective Tumor Response Rate
|
5 percentage of patients
Interval 1.0 to 25.0
|
0 percentage of patients
Interval 0.0 to 34.0
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: Because so few responses were observed, this exploratory outcome was not analyzed
Outcome measures
Outcome data not reported
Adverse Events
Erlotinib Plus HCQ (Hydroxychloroquine)
HCQ (Hydroxychloroquine)
Serious adverse events
| Measure |
Erlotinib Plus HCQ (Hydroxychloroquine)
n=19 participants at risk
Erlotinib at 150mg QD and HCQ at escalating doses (400mg, 600mg, 800mg and 1000mg QD)
|
HCQ (Hydroxychloroquine)
n=8 participants at risk
HCQ at escalating doses (400mg, 600mg, 800mg, and 1000mg QD)
|
|---|---|---|
|
Skin and subcutaneous tissue disorders
rash
|
5.3%
1/19 • Number of events 1
|
0.00%
0/8
|
|
Gastrointestinal disorders
nausea
|
5.3%
1/19 • Number of events 1
|
0.00%
0/8
|
|
Gastrointestinal disorders
dehydration
|
5.3%
1/19 • Number of events 1
|
0.00%
0/8
|
|
Skin and subcutaneous tissue disorders
nail changes
|
5.3%
1/19 • Number of events 1
|
0.00%
0/8
|
|
Blood and lymphatic system disorders
anemia
|
5.3%
1/19 • Number of events 1
|
0.00%
0/8
|
|
Respiratory, thoracic and mediastinal disorders
pneumonitis
|
5.3%
1/19 • Number of events 1
|
0.00%
0/8
|
Other adverse events
| Measure |
Erlotinib Plus HCQ (Hydroxychloroquine)
n=19 participants at risk
Erlotinib at 150mg QD and HCQ at escalating doses (400mg, 600mg, 800mg and 1000mg QD)
|
HCQ (Hydroxychloroquine)
n=8 participants at risk
HCQ at escalating doses (400mg, 600mg, 800mg, and 1000mg QD)
|
|---|---|---|
|
Skin and subcutaneous tissue disorders
rash
|
52.6%
10/19 • Number of events 10
|
0.00%
0/8
|
|
Gastrointestinal disorders
diarrhea
|
47.4%
9/19 • Number of events 9
|
0.00%
0/8
|
|
Gastrointestinal disorders
nausea
|
47.4%
9/19 • Number of events 9
|
37.5%
3/8 • Number of events 3
|
|
General disorders
fatigue
|
36.8%
7/19 • Number of events 7
|
12.5%
1/8 • Number of events 1
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place