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Hydroxychloroquine With or Without Erlotinib in Advanced Non-small Cell Lung Cancer (NSCLC)

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ClinicalTrials.gov Identifier: NCT01026844
Recruitment Status : Terminated (slow enrollment)
First Posted : December 4, 2009
Results First Posted : July 31, 2013
Last Update Posted : January 30, 2017
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Lecia V. Sequist, Massachusetts General Hospital

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Non-small Cell Lung Cancer
Interventions Drug: erlotinib
Drug: hydroxychloroquine
Enrollment 27
Recruitment Details Twenty-seven patients were enrolled between August 2007 and May 2010. They were all patients at Mass General Hospital Cancer Center
Pre-assignment Details  
Arm/Group Title Erlotinib Plus HCQ (Hydroxychloroquine) HCQ (Hydroxychloroquine)
Hide Arm/Group Description Erlotinib at 150mg QD and HCQ at escalating doses (400mg, 600mg, 800mg and 1000mg QD) HCQ at escalating doses (400mg, 600mg, 800mg, and 1000mg QD)
Period Title: Overall Study
Started 19 8
Completed 19 8
Not Completed 0 0
Arm/Group Title Erlotinib Plus HCQ (Hydroxychloroquine) HCQ (Hydroxychloroquine) Total
Hide Arm/Group Description Erlotinib at 150mg QD and HCQ at escalating doses (400mg, 600mg, 800mg and 1000mg QD) HCQ at escalating doses (400mg, 600mg, 800mg, and 1000mg QD) Total of all reporting groups
Overall Number of Baseline Participants 19 8 27
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 8 participants 27 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
9
  47.4%
6
  75.0%
15
  55.6%
>=65 years
10
  52.6%
2
  25.0%
12
  44.4%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 19 participants 8 participants 27 participants
65
(27 to 73)
61
(48 to 76)
64
(27 to 76)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 8 participants 27 participants
Female
10
  52.6%
5
  62.5%
15
  55.6%
Male
9
  47.4%
3
  37.5%
12
  44.4%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 19 participants 8 participants 27 participants
19 8 27
1.Primary Outcome
Title Describe the Number and Type of Observed Dose Limiting Toxcities
Hide Description 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.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Erlotinib Plus HCQ (Hydroxychloroquine) HCQ (Hydroxychloroquine)
Hide Arm/Group Description:
Erlotinib at 150mg QD and HCQ at escalating doses (400mg, 600mg, 800mg and 1000mg QD)
HCQ at escalating doses (400mg, 600mg, 800mg, and 1000mg QD)
Overall Number of Participants Analyzed 19 8
Measure Type: Number
Unit of Measure: participants
0 0
2.Secondary Outcome
Title Determine the Pharmacokinetic (PK) Parameters of Hydroxychloroquine (HCQ) Plus Erlotinib.
Hide Description 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.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title Erlotinib Plus HCQ (Hydroxychloroquine) HCQ (Hydroxychloroquine)
Hide Arm/Group Description:
Erlotinib at 150mg QD and HCQ at escalating doses (400mg, 600mg, 800mg and 1000mg QD)
HCQ at escalating doses (400mg, 600mg, 800mg, and 1000mg QD)
Overall Number of Participants Analyzed 13 8
Mean (Standard Deviation)
Unit of Measure: micromolar per gram
5.93  (2.51) 9.40  (5.85)
3.Secondary Outcome
Title Objective Tumor Response Rate
Hide Description Number 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
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Erlotinib Plus HCQ (Hydroxychloroquine) HCQ (Hydroxychloroquine)
Hide Arm/Group Description:
Erlotinib at 150mg QD and HCQ at escalating doses (400mg, 600mg, 800mg and 1000mg QD)
HCQ at escalating doses (400mg, 600mg, 800mg, and 1000mg QD)
Overall Number of Participants Analyzed 19 8
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of patients
5
(1 to 25)
0
(0 to 34)
4.Secondary Outcome
Title Correlate Epidermal Growth Factor Receptor (EGFR) Mutations and EGFR Amplification With Response to Treatment in Patients With Available Tumor Specimens.
Hide Description [Not Specified]
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Because so few responses were observed, this exploratory outcome was not analyzed
Arm/Group Title Erlotinib Plus HCQ (Hydroxychloroquine) HCQ (Hydroxychloroquine)
Hide Arm/Group Description:
Erlotinib at 150mg QD and HCQ at escalating doses (400mg, 600mg, 800mg and 1000mg QD)
HCQ at escalating doses (400mg, 600mg, 800mg, and 1000mg QD)
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Erlotinib Plus HCQ (Hydroxychloroquine) HCQ (Hydroxychloroquine)
Hide Arm/Group Description Erlotinib at 150mg QD and HCQ at escalating doses (400mg, 600mg, 800mg and 1000mg QD) HCQ at escalating doses (400mg, 600mg, 800mg, and 1000mg QD)
All-Cause Mortality
Erlotinib Plus HCQ (Hydroxychloroquine) HCQ (Hydroxychloroquine)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Erlotinib Plus HCQ (Hydroxychloroquine) HCQ (Hydroxychloroquine)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/19 (31.58%)      0/8 (0.00%)    
Blood and lymphatic system disorders     
anemia   1/19 (5.26%)  1 0/8 (0.00%)  0
Gastrointestinal disorders     
nausea *  1/19 (5.26%)  1 0/8 (0.00%)  0
dehydration *  1/19 (5.26%)  1 0/8 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
pneumonitis *  1/19 (5.26%)  1 0/8 (0.00%)  0
Skin and subcutaneous tissue disorders     
rash *  1/19 (5.26%)  1 0/8 (0.00%)  0
nail changes *  1/19 (5.26%)  1 0/8 (0.00%)  0
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Erlotinib Plus HCQ (Hydroxychloroquine) HCQ (Hydroxychloroquine)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   15/19 (78.95%)      4/8 (50.00%)    
Gastrointestinal disorders     
diarrhea *  9/19 (47.37%)  9 0/8 (0.00%)  0
nausea *  9/19 (47.37%)  9 3/8 (37.50%)  3
General disorders     
fatigue *  7/19 (36.84%)  7 1/8 (12.50%)  1
Skin and subcutaneous tissue disorders     
rash *  10/19 (52.63%)  10 0/8 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
Early termination of study leading to small numbers of subjects analyzed
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Lecia Sequist, MD
Organization: Massachusetts General Hospital
Phone: 617-724-4000
Responsible Party: Lecia V. Sequist, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01026844     History of Changes
Other Study ID Numbers: 07-037
OSI4251s ( Other Identifier: Genentech )
First Submitted: December 2, 2009
First Posted: December 4, 2009
Results First Submitted: November 25, 2012
Results First Posted: July 31, 2013
Last Update Posted: January 30, 2017