Dose escalation study of imatinib, 400mg/day, 600mg/day, 800mg/day, to determine the efficacy of each imatinib treatment in eliminating parasitemia along with the safety and tolerability of each treatment. Standard of care rescue drug is dihydroartemisinin-piperaquine.

Plasmodium Falciparum Malaria

Imatinib

Dihydroartemisinin-piperaquine

A Tuc

Imatinib's Effect on the Suppression of Malaria Parasites in Patients With Uncomplicated Plasmodium Falciparum Malaria

Parasite clearance was determined by assessing the parasite count in blood, using thin film, thick film and qPCR analysis

28-day cure rate was defined as the percentage of participants with blood parasite count of zero after 28 days of treatment and no evidence of recurrent infection with the same parasite genotype after reduction of the asexual parasitemia. Follow up after treatment will only be performed in the case of complete clearance of parasites at D5 due to Imatinib treatment.

Adverse events (AEs) are defined as events possibly related to the study drug as judged by physician that occur within 1 week of beginning treatment with imatinib.
Incidence, severity, drug-relatedness, seriousness of adverse events
Laboratory values (biochemistry and haematology)
Vital signs

HuLow

Purdue University

University of Turin, Italy

Università degli Studi di Sassari

Hue University

Dose escalation of sorafenib combined with hydroxychloroquine (HCQ) to a maximum of sorafenib 400 mg PO BID plus HCQ 400 mg PO QD.
Drugs are given on an intermittent schedule of days 1-5/week in a 28-day cycle.
Sorafenib alone is given in cycle 1, and HCQ is added in cycle 2.

Refractory or Relapsed Solid Tumors

dose escalation of sorafenib combined with hydroxychloroquine (HCQ) to a maximum of sorafenib 400 mg PO BID plus HCQ 400 mg PO QD.
Drugs are given on an intermittent schedule of days 1-5/week in a 28-day cycle.
Sorafenib alone is given in cycle 1, and HCQ is added in cycle 2.

Sorafenib combined with Hydroxychloroquine

Cancer Therapy and Research Center at UTHSCSA

Oral Hydroxychloroquine Plus Oral Sorafenib to Treat Patients With Refractory or Relapsed Solid Tumors

A Phase I Dose-Escalation Trial of Oral Hydroxychloroquine Plus Oral Sorafenib to Treat Patients With Refractory or Relapsed Solid Tumors

To assess the toxicities of combining sorafenib plus HCQ in this patient population

The University of Texas Health Science Center at San Antonio

erltoinib 150mg per day plus HCQ in esclating doses of 400mg, 600mg, 800mg and 1000mg per day

hydroxychloroquine given at escalating doses of 400mg, 600mg, 800mg and 1000mg per day

Erlotinib at 150mg QD and HCQ at escalating doses (400mg, 600mg, 800mg and 1000mg QD)

Erlotinib Plus HCQ (Hydroxychloroquine)

HCQ at escalating doses (400mg, 600mg, 800mg, and 1000mg QD)

HCQ (Hydroxychloroquine)

Total

Sex: Female, Male

Region of Enrollment

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.

Describe the Number and Type of Observed Dose Limiting Toxcities

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.

Determine the Pharmacokinetic (PK) Parameters of Hydroxychloroquine (HCQ) Plus Erlotinib.

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

Objective Tumor Response Rate

Correlate Epidermal Growth Factor Receptor (EGFR) Mutations and EGFR Amplification With Response to Treatment in Patients With Available Tumor Specimens.

Overall Study

Lecia Sequist, MD

Non-small Cell Lung Cancer

erlotinib

hydroxychloroquine

Massachusetts General Hospital

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

A Phase I Study of Hydroxychloroquine With or Without Erlotinib in Advanced NSCLC

Lecia V. Sequist

Genentech, Inc.

Erlotinib 150 mg oral daily plus Hydroxychloroquine (HCQ) 1000 mg oral daily

Erlotinib: 150 mg taken orally once daily

Erlotinib

Erlotinib: 150 mg taken orally once daily
Hydroxychloroquine: 1000 mg taken orally once daily after erlotinib

Erlotinib and Hydroxychloroquine

Smoking History

Histology

Brain metastases

Prior chemotherapy

A measure of progression-free survival in patients with advanced non small-cell lung cancer (NSCLC) and EGFR mutations treated with erlotinib as compared with patients treated with erlotinib plus hydroxychloroquine (HCQ). Disease progression is defined as at least a 20% increase in the sum of the longest diameter of target lesions, as seen on CT scan, or the appearance of one or more new lesions on CT scan.

Median Progression Free Survival

This trial can detect a difference in proportions alive without progression at 9 months from 50% in the erlotinib arm to 77% in the erlotinib plus hydroxychloroquine (HCQ) arm, using an alpha of 0.15 and power of 85%, using the two-sided Likelihood Ratio test. Progression is defined as at least a 20% increase in the size of existing lesions or the appearance of one or more new lesions.

Nine-month Progression-free Survival Rate

To evaluate the safety of treatment with erlotinib with and without hydroxychloroquine (HCQ). All participants receiving study treatment were evaluated for safety. Parameters included laboratory tests, hematological abnormalities, physical exam findings and spontaneous reports of adverse events reported by participants. Toxicities were evaluated and graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life-threatening, Grade 5 = fatal.

Treatment Related Toxicity, > 10% Frequency, Any Grade

Response is assessed via spiral CT scan, done at baseline and after every 2 cycles of study treatment. Standard RECIST (Response Evaluation Criteria in Solid Tumors) was used. Complete Response (CR) = disappearance of all target lesions; Partial Response (PR) = at least a 30% decrease in the size of target lesions, as compared to baseline; Progressive Disease (PD) = at least at 20% increase in the size of target lesions, or the appearance of one or more new lesions; Stable Disease (SD) = neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease.
Response rate = CR + PR. Disease control rate = CR + PR + SD

Objective Tumor Response Rate Following Treatment With Erlotinib and With Erlotinib/HCQ.

Overall Survival of Patients Treated With Erlotinib and With Erlotinib/HCQ

Serial circulating tumor cell (CTC) analyses will be performed on peripheral blood and correlated with disease response.

Circulating Tumor Cell Quantification

Correlation of molecular and genetic tumor characteristics with disease response. Genomic DNA will be extracted from tumor tissue and direct sequencing analysis will be performed to identify additional mutations.

EGFR Mutational Status

[18F]-FMISO-PET/CT was performed on a 64-slice PET/CT scanner and tracer uptake was assessed using SUV (standardized uptake value), normalizing the radioactivity measured in tissue by the injected dose and the body weight of the patient. Mean and maximum SUV and threshold volume of FMISO uptake were measured to quantify the extent of hypoxia in the primary tumor. Imaging was performed before and after initiation of therapy with erlotinib.

Percent of Participants in Which FMISO-PET ([18F]-Fluoromisonidazole-positron Emission Tomography) is Able to Detect and Quantify Changes in Tumor Hypoxia After Erlotinib.

Maria Kempner

1000 mg taken orally once daily after erlotinib

malaria/tyrosine

Imatinib's Effect on the Suppression of Malaria Parasites in Patients With Uncomplicated Plasmodium Falciparum Malaria

Oral Hydroxychloroquine Plus Oral Sorafenib to Treat Patients With Refractory or Relapsed Solid Tumors

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

Erlotinib With or Without Hydroxychloroquine in Chemo-Naive Advanced NSCLC and (EGFR) Mutations

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