Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01839955
Other study ID # CASE8512
Secondary ID NCI-2013-00599
Status Completed
Phase Phase 1
First received April 23, 2013
Last updated October 28, 2016
Start date September 2013
Est. completion date October 2016

Study information

Verified date October 2016
Source Case Comprehensive Cancer Center
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug Administration
Study type Interventional

Clinical Trial Summary

This phase I trial studies the side effects and best dose of quinacrine dihydrochloride when given together with erlotinib hydrochloride and to see how well it works in treating patients with stage IIIB-IV non-small cell lung cancer. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as quinacrine dihydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving erlotinib hydrochloride together with quinacrine dihydrochloride may kill more tumor cells


Description:

PRIMARY OBJECTIVES:

I. To assess the safety and tolerability of the combination of erlotinib (erlotinib hydrochloride) and quinacrine (quinacrine dihydrochloride) in patients with advanced non-small-cell lung cancer.

II. To determine the recommended Maximum Tolerated Dose (MTD) of the combination of erlotinib and quinacrine in patients with advanced non-small-cell lung cancer.

SECONDARY OBJECTIVES:

I. To describe the dose limiting toxicity of the erlotinib and quinacrine combination.

II. To determine the pharmacokinetic profile of the erlotinib and quinacrine combination.

III. To determine objective response rate (complete response [CR]+partial response [PR]) and clinical benefit rate (CR+PR+ stable disease [SD]) of the erlotinib and quinacrine combination.

IV. To estimate overall survival (OS)

OUTLINE: This is a phase I, dose escalation study of quinacrine dihydrochloride

Escalation Portion: Patients receive erlotinib hydrochloride orally (PO)daily on days 1-28 and quinacrine dihydrochloride PO thrice daily (TID) on days, 1-7 and PO daily from days 8-28.

After Maximum Tolerated Dose is established: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive erlotinib hydrochloride PO daily on days 1-28.

ARM II: Patients receive erlotinib hydrochloride PO and quinacrine dihydrochloride PO daily (TID) on days, 1-7 and PO daily from days 8-28.

In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.


Recruitment information / eligibility

Status Completed
Enrollment 12
Est. completion date October 2016
Est. primary completion date October 2016
Accepts healthy volunteers No
Gender Both
Age group 18 Years and older
Eligibility Inclusion Criteria:

- Patients must have histologically or cytologically confirmed incurable malignancy that is surgically unresectable locally advanced, recurrent, or metastatic (stage IIIB/IV) non-small cell lung cancer (NSCLC). Patients with adenocarcinoma, squamous cell carcinoma, large cell carcinoma and sarcomatoid carcinoma will be eligible.

- Patients must have received at least one platinum-containing regimen for the treatment of advanced or metastatic disease (except for EGFR-mutant patients). Prior maintenance therapy is allowed and will be considered as the same line of therapy when continued without discontinuation after initiation of a treatment regimen. NSCLC with documented EGFR mutation will be eligible after progression on an EGFR-TKI alone. NSCLC with other molecular targets, such as fusion gene involving the anaplastic lymphoma kinase (ALK) gene (such as echinoderm microtubule associated protein like 4 [EML4]-ALK) or ROS-1 will be eligible if they have progressed on targeted agents (ALK inhibitor) and chemotherapy or are not a candidate for chemotherapy. Adjuvant/neoadjuvant chemotherapy or chemoradiation is considered a line of therapy if < 12 months have elapsed between the last dose and the date of recurrence. Combined treatment with chemotherapy and radiation constitutes a single regimen.

- Eastern Cooperative Oncology Group (ECOG) performance status = 2

- Life expectancy of = 12 weeks, in the opinion of and as documented by the investigator

- Hemoglobin = 9.0 g/dl (transfusion and/or growth factor support allowed)

- Absolute neutrophil count (ANC) = 1,500/mcL

- Platelet count = 100 x 10^9 L

- Alkaline phosphatase < 2.5 X institutional upper limit of normal (in subjects with no liver metastasis and < 5.0 upper limit of normal [ULN] in subjects with liver metastasis)

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2.5 X institutional upper limit of normal (in subjects with no liver metastasis and < 5.0 ULN in subjects with liver metastasis)

- Serum creatinine = 1.5 x ULN or creatinine clearance = 50 mL/min

- Serum total bilirubin = 1.5 x ULN OR total bilirubin = 4.0 ULN with direct bilirubin = 1.5 x ULN in patients with well documented Gilbert syndrome

- Patients who are receiving therapeutic anticoagulation with heparin are allowed to participate provided that no prior evidence of underlying abnormality exists in these parameters. Patients on warfarin are eligible provided they are on stable doses of warfarin and there is close monitoring of INR.

- Resolution of any toxic effects of prior therapy (including radiotherapy) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0, grade = 1 (with the exception of alopecia and = grade 2 neuropathy); subject must have recovered from significant surgery-related complications

- Women of childbearing potential must have a negative pregnancy test performed within 48 hours prior to the start of the study drug

- Women of child-bearing potential and men must agree to use adequate contraception (double barrier method of birth control or abstinence) prior to study entry, for the duration of study participation and for 90 days after completing the last investigational drug dose; should a woman become pregnant or suspect that she is pregnant while she or her partner is participating in this study, she should inform the treating physician immediately

- Subjects must have the ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Patients with previous anti-cancer chemotherapy, immunotherapy or investigational agents = 3 weeks prior to the first day of study defined treatment. NSCLC patients with EGFR mutation can enroll within 7 days of discontinuing EGFR-TKI. Palliative radiation < 1 week before the start of treatment (lesions subjected to radiotherapy may not be used as target lesions). Patients who receive gamma knife radiosurgery for brain metastases within 1 week prior to treatment start.

- Patients with unknown status of EGFR mutation (only for patients with adenocarcinoma histology)

- Patients that have had major surgery = 3 weeks or minor surgery (e.g. talc pleurodesis, excisional biopsy, etc) = 1 week prior to the first day of study defined treatment.

- History of cardiac disease: congestive heart failure defined as class II to IV per New York Heart Association (NYHA) classification; active coronary artery disease (CAD); previously diagnosed bradycardia or other cardiac arrhythmia defined as = grade 2 according to NCI-CTCAE (version 4.0), or uncontrolled hypertension; myocardial infarction occurred within 6 months prior to study entry (myocardial infarction occurred > 6 months prior to study entry is permitted)

- Patients with clinically unstable central nervous system (CNS) metastasis (to be enrolled in the study, subjects must have confirmation of stable disease by magnetic resonance imaging [MRI] or computed tomography [CT] scan within 4 weeks of the first day of study defined treatment and have CNS metastases well controlled by steroids, anti-epileptics or other symptom-relieving medications)

- Patients with significant gastrointestinal disorder that, in the opinion of the investigator, could interfere with absorption of quinacrine and/or erlotinib (eg, Crohn's disease, small or large bowel resection, malabsorption syndrome)

- Patients with any known contraindication to treatment with, including hypersensitivity to quinacrine or erlotinib

- Patients with active clinically serious infections defined as = grade 2 according to NCI CTCAE, version 4.0

- Patients with substance abuse, medical, psychological or social conditions that may, in the opinion of the Investigator, interfere with the patient's participation in the study or evaluation of the study results

- Any other condition that is unstable or which could jeopardize the safety of the patient and his/her protocol compliance

- History of incurable malignancy other than NSCLC within the 5 years prior to start of treatment, with the exceptions of adequately treated intraepithelial carcinoma of the cervix uteri; prostate carcinoma with a prostate-specific antigen value <0.2 ng/mL; or basal or squamous-cell carcinoma of the skin.

- Pregnant or breastfeeding women and adults of reproductive potential not employing an effective method of birth control are excluded from this study because quinacrine is category N agent with the potential for teratogenic or abortifacient effects; these potential risks may also apply to other agents used in this study

- Patients with previously known infection with human immunodeficiency virus (HIV) or active viral hepatitis are ineligible because of the potential for pharmacokinetic interactions with quinacrine; (diagnostic testing for these infections will be done only if clinically indicated)

- Patients with known Glucose-6-phosphate deficiency, psoriasis, porphyria and psychosis (quinacrine may exacerbate the symptoms of these disorders)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms


Intervention

Drug:
erlotinib hydrochloride
Dose Escalation Group: Begins day 1: given 150mg daily, orally Extension Group: Begins Day 1: 150mg daily, orally
quinacrine dihydrochloride - Escalation dose
Begins Day 8: Loading dose (first cycle only) 50mg three times daily for 7 days followed by 21 days of 50mg maintenance dose. Level -1: Loading dose (50mg three times daily for 7 days), maintenance dose (50mg every other day for three weeks). Level 1 [starting dose]: Loading dose (50mg three times daily for 7 days), maintenance dose (50mg daily for three weeks). Level 2: Loading dose (100mg three times daily for 7 days), maintenance dose (100mg every other day for three weeks). Level 3: Loading dose (150mg three times daily for 7 days), maintenance dose (200mg every other day for three weeks). Level 4: Loading dose (200mg three times daily for 7 days), maintenance dose (400mg every other day for three weeks). Subsequent patient cohort(s) will be enrolled depending on the safety and tolerability of subjects
Other:
laboratory biomarker analysis
Correlative studies
pharmacological study
Correlative studies
Drug:
quinacrine dihydrochloride - Extension dose
Participants will be treated at recommended dose from expansion group to confirm tolerability and evaluate early response

Locations

Country Name City State
United States University Hospitals Cleveland Medical Center, Seidman Cancer Center, Case Comprehensive Cancer Cleveland Ohio

Sponsors (1)

Lead Sponsor Collaborator
Neelesh Sharma MD PhD

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Maximum tolerated dose (MTD) of quinacrine dihydrochloride in combination of erlotinib hydrochloride determined by dose-limiting toxicities 28 days Yes
Primary Progression Free Survival (PFS) Estimated by Kaplan-Meier method and the difference between two treatment arms will be evaluated by log-rank test. Date of randomization to the date of disease progression or the date of death, assessed up to 2 years No
Secondary Pharmacokinetic parameters after 2 months (2 cycles) No
Secondary Objective tumor response rate (ORR) (complete response and partial response) evaluated by revised Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria Estimated based on the number of responses by excluding the dropouts who are not evaluable for response using a binomial distribution. Up to 2 years No
Secondary Disease stabilization rate (complete response, partial response and stable disease) The confidence intervals for them will be estimated using Wilson's method. Up to 2 years No
Secondary Baseline expression of intracellular inhibitor of the nuclear factor kappa B (IkappaB) or NFkappaB gene signature in determining survival or response Baseline up to 2 years No
Secondary Overall survival (OS) Estimated by Kaplan-Meier method and the difference between two treatment arms will be evaluated by log-rank test. Identified by Cox model or extended Cox model. Chi-square test or Fisher's exact test will be used to examine the difference of response rate between two treatment arms. Date of randomization to the date of death, assessed up to 2 years No
See also
  Status Clinical Trial Phase
Completed NCT01664754 - Exemestane, Pemetrexed Disodium, and Carboplatin in Treating Post-Menopausal Women With Stage IV Non-Small Cell Lung Cancer Phase 1
Completed NCT02451930 - A Study of the Combination of Necitumumab (LY3012211) and Pembrolizumab (MK3475) in Participants With NSCLC Phase 1
Withdrawn NCT02106559 - Photodynamic Therapy During Surgery in Treating Patients With Pleural Malignancy N/A
Completed NCT02364609 - Pembrolizumab and Afatinib in Patients With Non-small Cell Lung Cancer With Resistance to Erlotinib Phase 1
Terminated NCT02495896 - Recombinant EphB4-HSA Fusion Protein With Standard Chemotherapy Regimens in Treating Patients With Advanced or Metastatic Solid Tumors Phase 1
Completed NCT01935336 - Study of Ponatinib in Patients With Lung Cancer Preselected Using Different Candidate Predictive Biomarkers Phase 2
Withdrawn NCT01971489 - Buparlisib, Gemcitabine Hydrochloride, and Cisplatin in Treating Patients With Advanced Solid Tumors Phase 1
Terminated NCT01193868 - RO4929097 in Treating Patients With Advanced Non-Small Cell Lung Cancer Who Have Recently Completed Treatment With Front-Line Chemotherapy Phase 2
Completed NCT00963807 - Trial Comparing the Use of FLT PET to Standard CT to Assess Treatment Response of Neoadjuvant Docetaxel and Cisplatin in Stage IB-IIIA Resectable NSCLC Phase 2
Completed NCT00986674 - Carboplatin and Paclitaxel Combined With Cetuximab and/or IMC-A12 in Patients With Advanced Non-Small Cell Lung Cancer Phase 2
Completed NCT00085280 - Erlotinib in Treating Patients With Stage IIIB, Stage IV, or Recurrent Non-Small Cell Lung Cancer N/A
Completed NCT00087412 - S0341: Erlotinib in Treating Patients With Advanced Primary Non-Small Cell Lung Cancer Phase 2
Completed NCT00052338 - Bortezomib Plus Gemcitabine and Carboplatin in Treating Patients With Advanced or Recurrent Non-Small Cell Lung Cancer Phase 1
Completed NCT00006929 - Suramin, Paclitaxel, and Carboplatin in Treating Patients With Stage IIIB or Stage IV Non-small Cell Lung Cancer Phase 2
Completed NCT02879994 - Pembrolizumab in Treating Patients With EGFR Mutant, Tyrosine Kinase Inhibitor Naive Advanced Non-Small Cell Lung Cancer Phase 2
Completed NCT03305380 - Radiomics to Identify Patients at Risk for Developing Pneumonitis, Differentiate Immune Checkpoint Inhibitor-induced Pneumonitis From Other Lung Inflammation and Distinguish Tumour Pseudo-progression From Real Tumour Growth
Completed NCT02728596 - S1415CD, Trial Assessing CSF Prescribing Effectiveness and Risk (TrACER) N/A
Completed NCT02858869 - Pembrolizumab and Stereotactic Radiosurgery for Melanoma or Non-Small Cell Lung Cancer Brain Metastases Phase 1
Completed NCT02897375 - Palbociclib With Cisplatin or Carboplatin in Advanced Solid Tumors Phase 1
Terminated NCT02566421 - Genomic Sequencing in Determining Treatment in Patients With Metastatic Cancer or Cancer That Cannot Be Removed by Surgery N/A