Non-small Cell Lung CancerPhase 2NCT01649947
Modulation of Autophagy in Patients With Advanced/Recurrent Non-small Cell Lung Cancer - Phase II
A Phase 2 study testing Paclitaxel, Carboplatin and Hydroxychloroquine in people with Non-small Cell Lung Cancer and Advanced Non-small Cell Lung Cancer, run by Rutgers, The State University of New Jersey at 2 sites in United States.
Trial summary
The purpose of this study is to examine the combination of one standard treatment for lung cancer plus an additional drug, hydroxychloroquine. The standard treatment for lung cancer being used includes 2 chemotherapy drugs, called paclitaxel and carboplatin. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Non-small Cell Lung Cancer, Advanced Non-small Cell Lung Cancer, Recurrent Non-small Cell Lung Cancer
- What is being tested?
- Paclitaxel, Carboplatin and Hydroxychloroquine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 2 sitesUnited States
- Study dates
- 23 Dec 2011to 30 Jun 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed a protocol-specific informed consent.
- 18 years of age or older.
- ECOG Performance Status 0 or 1.
- Cancer criteria:
- Histologically or cytologically confirmed non-small cell lung cancer. Mixed tumors will be categorized by the predominant cell type unless small cell elements are present, in which case the patient is ineligible. Cytologic or histologic elements can be established on metastatic tumor aspirate or biopsy. Sputum cytology alone is not sufficient.
- Advanced stage NSCLC (stage IVa ((malignant pleural effusion (is now staged as stage IVa by the most recent staging system), or stage IV, or recurrent disease)).
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- Measurable disease according to RECIST criteria.
- Patient with CNS metastasis are required to have stable disease documented by being off treatment (surgery, or Whole Brain radiation therapy) for at least 2 weeks, and four (4) weeks is preferred. No delay in onset of therapy is required for those patients who undergo stereotactic RT to the brain lesion(s). A contrast enhanced brain CT or brain MRI is required within 35 days of enrollment. Patients with brain metastases who qualify for protocol therapy will be included in Cohort 2 (ineligible for treatment with Bevacizumab).
- Prior radiation to sites other than the brain is allowed, if completed at least 2 weeks before treatment and provided that all radiation-related toxicities have resolved to ≤ Grade 1. Stereotactic irradiation to any site excludes the need for a waiting period.
- Laboratory requirements
- Adequate organ function, as evidenced by ALL the following:
- absolute neutrophil count (ANC) ≥ 1500/mm³
- platelet count ≥ 100,000/mm³
- hemoglobin ≥ 9 gm/dL
- total bilirubin ≤ 1.5 x ULN; if patient has Gilbert's disease, then patient must have isolated hyperbilirubinemia (e.g. no other liver function test abnormality), with maximum bilirubin ≤ 2 X institutional ULN.
- AST and ALT ≤ 2.5 x ULN in the absence of liver metastases; AST and ALT ≤ 5 x ULN in the presence of liver metastases
- alkaline phosphatase ≤ 2.5 x ULN
- creatinine ≤ 1.5 X institutional ULN or calculated creatinine clearance ≥ 60 ml/min as estimated using the Cockcroft-Gault formula.
- Comorbidities For Cohort 1: (Bevacizumab eligible)
- For patients who have had a major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to enrollment, or anticipate the need for such while on active treatment, may participate and receive Bevacizumab at the start of the second or third cycle as they would under standard care. Placement of vascular access device is not considered major surgery, but the incision must have healed before initiation of treatment.
- Patients must have a systolic blood pressure ≤ 150 mm Hg and diastolic blood pressure ≤ 100 mm Hg (the use of antihypertensive medications to achieve these goals is allowed).
- Adequate organ function
- INR ≤ 1.5 and aPTT WNL.
- Urine Protein Creatinine (UPC) ratio < 1.0 or 24 hour urine protein ratio < 1000 mg
- UPC ratio of spot urine is an estimation of the 24 urine protein excretion. A UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 gm. To obtain a UPC ratio:
- Obtain at least 4 mL of a random urine sample
- Determine protein and creatinine concentration
- Calculate the UPC using one of the following formulae [urine protein]/[urine creatinine] - if both values are reported in mg/dL [(urine protein) x 0.088]/[urine creatinine] - if urine creatinine is reported in mmol/L
- For ALL (Cohort 1 and Cohort 2):
- Women must:
- Have a negative serum or urine pregnancy test within 7 days prior to study entry if she is a woman of child-bearing potential, OR
- Be at least one year post-menopausal, OR
- Be surgically sterile
- Patients of childbearing or child fathering potential must be willing to use an acceptable method of birth control prior to study entry and for the duration of the study. Acceptable methods of contraception include hormonal, barrier methods, intrauterine device, tubal ligation/vasectomy or abstinence.
Who cannot join
- Cancer criteria:
- No prior cytotoxic chemotherapy or targeted therapy in the advanced or metastatic setting. Post-operative adjuvant therapy for previously resected NSCLC is allowed as long as the last dose was given greater than 1 year before study entry, and there is current evidence of disease progression.
- No active malignancy other than NSCLC. Patients with a history of basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, or ductal or lobular carcinoma in situ of the breast within the past 3 years must have been treated with curative intent. Patients with a history of prior malignancy are eligible provided they were treated with curative intent and have been free of disease for > 3 years.
- Comorbidities
- For Cohort 1: (Bevacizumab eligible)
- No history of gross hemoptysis (defined as bright red blood of a half-teaspoon or more) within 3 months prior to enrollment.
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- None of the following conditions within 6 months prior to enrollment: myocardial infarction, stroke or symptomatic peripheral vascular disease.
- No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to enrollment.
- No serious non-healing wound, ulcer or bone fracture.
- Patients must not have unstable angina or NYHA classification of congestive heart failure of Grade ≥ 2.
- No history of significant vascular disease (eg aortic aneurysm).
- No current or recent (within 28 days of enrollment) full dose anticoagulants or thrombolytic agents.
- For Cohort 2 (Bevacizumab ineligible):
- None of the following conditions within 6 months prior to enrollment: myocardial infarction, stroke or symptomatic peripheral vascular disease.
- Patients must not have unstable angina or NYHA classification of congestive heart failure of Grade ≥ 2.
- No history of significant vascular disease (eg aortic aneurysm).
- For ALL (Cohort 1 and Cohort 2):
- Patients must not have psoriasis or porphyria.
- No known hypersensitivity to 4-aminoquinoline compound.
- Patients must not have known or suspected G-6P deficiency.
- No know bleeding diathesis or coagulopathy.
- No known GI pathology that would interfere with drug bioavailability.
- No peripheral or sensory neuropathy > Grade 1 at study entry.
- No known prior hypersensitivity to carboplatin, paclitaxel, bevacizumab or hydroxychloroquine or any of their components.
- No ongoing or active infection at study entry.
- Patients must not be receiving treatment for rheumatoid arthritis or systemic lupus erythematosus.
- Patients must not have HIV or be taking HAART therapy.
- Patients must not have a history of any condition (social or medical) that, in the opinion of the Investigator, might interfere with the patient's compliance with the protocol or pose additional or unacceptable risk to the patient.
- Women must NOT be pregnant or breastfeeding.
- Must not be taking hydroxychloroquine for treatment or prophylaxis of malaria.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Robert Wood Johnson University Hospital at Hamilton
Hamilton, New Jersey, 08690
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08901
About this study
Official title: Modulation of Autophagy With Hydroxychloroquine in Patients With Advanced/Recurrent Non-small Cell Lung Cancer - a Phase II Study. A Study of The Cancer Institute of New Jersey Oncology Group (CINJOG)
The purpose of this study is to examine the combination of one standard treatment for lung cancer plus an additional drug, hydroxychloroquine. The standard treatment for lung cancer being used includes 2 chemotherapy drugs, called paclitaxel and carboplatin. Some patients who have a specific type of lung cancer can also receive another drug, a drug that targets blood vessels, called bevacizumab (also known as avastin). Hydroxychloroquine is an FDA approved drug for the treatment of malaria, rheumatoid arthritis and lupus erythematosis.
- Conditions
- Non-small Cell Lung Cancer, Advanced Non-small Cell Lung Cancer, Recurrent Non-small Cell Lung Cancer
- Being tested
- Paclitaxel, Carboplatin, Hydroxychloroquine, Bevacizumab
- Keywords
- Lung cancer, Non-small cell lung cancer, Advanced non-small cell lung cancer, Recurrent non-small cell lung cancer
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PaclitaxelDrug
Also called Taxol
Paclitaxel will be given at a dose of 200 mg/m2(by IV over 3 hours on Day 1). Cycles every 3 weeks for 4-6 Cycles.
Prior to receiving paclitaxel, all patients will receive the following premedication:
- Dexamethasone 20 mg po 12 and 6 hours prior to paclitaxel infusion (patients may be treated with dexamethasone 20 mg iv < 1 hour prior to infusion with paclitaxel if the patient did not take the oral dexamethasone)
- Diphenydramine 50 mg iv (or equivalent) < 1 hour prior to paclitaxel infusion
- Ranitidine 50 mg iv < 1 hour prior to paclitaxel infusion (alternatively other H2-blockers may be used)
CarboplatinDrug
Also called Paraplatin
Carboplatin will be given at AUC = 6 by IV over 15-30 minutes on Day 1 immediately following paclitaxel. Cycles every 3 weeks for 4-6 Cycles.
Also called Plaquenil
Hydroxychloroquine will be given as a flat dose of 200 mg orally BID (total daily dose of 400 mg). Cycles every 3 weeks for 4-6 Cycles.
BevacizumabDrug
Also called Avastin
Cohort 1 only:
Bevacizumab will be given by IV on Day 1 of each 21-day cycle at a dose of 15 mg/kg. Cycles every 3 weeks for 4-6 Cycles.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 2: Bevacizumab ineligible patients | Experimental | Paclitaxel 200mg/m2 IV over 3 hours Carboplatin AUC= 6 IV over 15-30 min Hydroxychloroquine 200 mg PO BID Receives: Drug: Paclitaxel; Drug: Carboplatin; Drug: Hydroxychloroquine |
| Cohort 1: Bevacizumab eligible patients | Experimental | Paclitaxel 200mg/m2 IV over 3 hours Carboplatin AUC= 6 IV over 15-30 min Bevacizumab 15 mg/kg IV over 90 min for Hydroxychloroquine 200 mg PO BID Receives: Drug: Paclitaxel; Drug: Carboplatin; Drug: Hydroxychloroquine; Drug: Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Antitumor Activity, as Measured by Tumor Response Rate of Hydroxychloroquine, Paclitaxel, Carboplatin, and Bevacizumab (for Eligible Patients) in Patients With Advanced or Recurrent NSCLC Cancer
Assessed using RECIST criteria. Determined using a Simon's two-stage minimax design with a 5% significance level and 80% power.
Measured: 6 years
Secondary outcomes (1)
Progression Free Survival (PFS)
Kaplan-Meier estimates of survival were calculated. The median survival times and 95% confidence intervals are presented.
Measured: 6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2012 (estimated)
- Study start23 Dec 2011
- Primary completion30 Jun 2015
- Study completion30 Jun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Non-small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Rutgers, The State University of New JerseyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rutgers, The State University of New Jersey
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Rutgers Cancer Institute of New Jersey
- Responsible party
- Sponsor
- Investigators
- Joseph Aisner, MD, Principal investigator, Rutgers Cancer Institute of New Jersey
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01649947
- Sponsor's protocol ID
- 0220110249
- Other IDs
- 0220110249, P30CA072720, NCI-2011-03731, 031105
- Status last verified
- Oct 2022
- First submitted
- 20 Jul 2012
- Last updated
- 21 Nov 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Modulation of Autophagy With Hydroxychloroquine in Patients With Advanced/Recurrent Non-small Cell Lung Cancer - a Phase II Study. A Study of The Cancer Institute of New Jersey Oncology Group (CINJOG)
- ClinicalTrials.gov ID
- NCT01649947
- Acronym / sponsor ID
- 0220110249
- Conditions
- Non-small Cell Lung Cancer, Advanced Non-small Cell Lung Cancer, Recurrent Non-small Cell Lung Cancer
- Keywords
- Lung cancer, Non-small cell lung cancer, Advanced non-small cell lung cancer, Recurrent non-small cell lung cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Rutgers, The State University of New JerseyUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), Rutgers Cancer Institute of New Jersey
- Study start
- 23 Dec 2011 (actual)
- Primary completion
- 30 Jun 2015 (actual)
- Study completion
- 30 Jun 2015 (actual)
- First posted
- 25 Jul 2012 (estimated)
- Results
- Posted 8 May 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to examine the combination of one standard treatment for lung cancer plus an additional drug, hydroxychloroquine. The standard treatment for lung cancer being used includes 2 chemotherapy drugs, called paclitaxel and carboplatin. Some patients who have a specific type of lung cancer can also receive another drug, a drug that targets blood vessels, called bevacizumab (also known as avastin). Hydroxychloroquine is an FDA approved drug for the treatment of malaria, rheumatoid arthritis and lupus erythematosis.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 2: Bevacizumab ineligible patients | Experimental | Drug: Paclitaxel, Drug: Carboplatin, Drug: HydroxychloroquinePaclitaxel 200mg/m2 IV over 3 hours Carboplatin AUC= 6 IV over 15-30 min Hydroxychloroquine 200 mg PO BID |
| Cohort 1: Bevacizumab eligible patients | Experimental | Drug: Paclitaxel, Drug: Carboplatin, Drug: Hydroxychloroquine, Drug: BevacizumabPaclitaxel 200mg/m2 IV over 3 hours Carboplatin AUC= 6 IV over 15-30 min Bevacizumab 15 mg/kg IV over 90 min for Hydroxychloroquine 200 mg PO BID |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (34 listed)
- Signed a protocol-specific informed consent.
- 18 years of age or older.
- ECOG Performance Status 0 or 1.
- Histologically or cytologically confirmed non-small cell lung cancer. Mixed tumors will be categorized by the predominant cell type unless small cell elements are present, in which case the patient is ineligible. Cytologic or histologic elements can be established on metastatic tumor aspirate or biopsy. Sputum cytology alone is not sufficient.
- Advanced stage NSCLC (stage IVa ((malignant pleural effusion (is now staged as stage IVa by the most recent staging system), or stage IV, or recurrent disease)).
Key exclusion criteria (30 listed)
- No prior cytotoxic chemotherapy or targeted therapy in the advanced or metastatic setting. Post-operative adjuvant therapy for previously resected NSCLC is allowed as long as the last dose was given greater than 1 year before study entry, and there is current evidence of disease progression.
- No active malignancy other than NSCLC. Patients with a history of basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, or ductal or lobular carcinoma in situ of the breast within the past 3 years must have been treated with curative intent. Patients with a history of prior malignancy are eligible provided they were treated with curative intent and have been free of disease for > 3 years.
- Comorbidities
- For Cohort 1: (Bevacizumab eligible)
- No history of gross hemoptysis (defined as bright red blood of a half-teaspoon or more) within 3 months prior to enrollment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PaclitaxelAlso: TaxolPaclitaxel will be given at a dose of 200 mg/m2(by IV over 3 hours on Day 1). Cycles every 3 weeks for 4-6 Cycles. Prior to receiving paclitaxel, all patients will receive the following premedication: * Dexamethasone 20 mg po 12 and 6 hours prior to paclitaxel infusion (patients may be treated with dexamethasone 20 mg iv < 1 hour prior to infusion with paclitaxel if the patient did not take the oral dexamethasone) * Diphenydramine 50 mg iv (or equivalent) < 1 hour prior to paclitaxel infusion * Ranitidine 50 mg iv < 1 hour prior to paclitaxel infusion (alternatively other H2-blockers may be used) | Drug | Cohort 1: Bevacizumab eligible patients, Cohort 2: Bevacizumab ineligible patients |
| CarboplatinAlso: ParaplatinCarboplatin will be given at AUC = 6 by IV over 15-30 minutes on Day 1 immediately following paclitaxel. Cycles every 3 weeks for 4-6 Cycles. | Drug | Cohort 1: Bevacizumab eligible patients, Cohort 2: Bevacizumab ineligible patients |
| HydroxychloroquineAlso: PlaquenilHydroxychloroquine will be given as a flat dose of 200 mg orally BID (total daily dose of 400 mg). Cycles every 3 weeks for 4-6 Cycles. | Drug | Cohort 1: Bevacizumab eligible patients, Cohort 2: Bevacizumab ineligible patients |
| BevacizumabAlso: AvastinCohort 1 only: Bevacizumab will be given by IV on Day 1 of each 21-day cycle at a dose of 15 mg/kg. Cycles every 3 weeks for 4-6 Cycles. | Drug | Cohort 1: Bevacizumab eligible patients |
Primary outcome
Antitumor Activity, as Measured by Tumor Response Rate of Hydroxychloroquine, Paclitaxel, Carboplatin, and Bevacizumab (for Eligible Patients) in Patients With Advanced or Recurrent NSCLC Cancer
Time frame: 6 years
Assessed using RECIST criteria. Determined using a Simon's two-stage minimax design with a 5% significance level and 80% power.
1 secondary outcome
Progression Free Survival (PFS)
Time frame: 6 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Nov 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joseph Aisner, MD principal investigator
Rutgers Cancer Institute of New Jersey
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Paclitaxel, Carboplatin and Hydroxychloroquine in people with Non-small Cell Lung Cancer and Advanced Non-small Cell Lung Cancer, run by Rutgers, The State University of New Jersey at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 34 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Antitumor Activity, as Measured by Tumor Response Rate of Hydroxychloroquine, Paclitaxel, Carboplatin, and Bevacizumab (for Eligible Patients) in Patients With Advanced or Recurrent NSCLC Cancer (time frame: 6 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Nov 2022.