AzTrials
AzTrials

Non-small Cell Lung CancerPhase 2NCT02737709

Paclitaxel Detection in NSCLC Treated With TC Regimen

A Phase 2 study testing Paclitaxel and Carboplatin regimen in people with Non-small Cell Lung Cancer, run by Sun Yat-sen University at 1 site in China.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

By detecting the blood concentration of paclitaxel (PTX), Investigator assume this research can identify the individual differences of PTX pharmacokinetics (PK) parameters (TC>0.05 refers to the duration of paclitaxel plasma concentration above 0.05 µmol/L) in Chinese non-small cell lung cancer (NSCLC) patients, and… Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Non-small Cell Lung Cancer
What is being tested?
Paclitaxel and Carboplatin regimen
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
51 participants
Where
1 siteChina
Study dates
Mar 2016to 25 Oct 2018
Phase
Phase 2
Are there results?
None posted in the registry

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 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age: 18 ~75 years
  • Pathology: Confirmed by pathology (histology or cytology) for advanced non-small cell lung cancer
  • Have indications of paclitaxel/carboplatin chemotherapy, suitable for paclitaxel chemotherapy (independent of clinical tumor stage or chemotherapy type or palliative chemotherapy lines)
  • At least one measurable tumor lesions (according to RECIST 1.1 criteria)
  • ECOG PS score: 0 to 2 points
  • Life expectancy: more than 3 months
  • Bone marrow reserve function is good, the function of organs (liver and kidney) is good, can satisfy the conditions of implementation chemotherapy. neutrophil count ≥1.5×109/l, platelet ≥75×109/l, hemoglobin >9g/dl, Total Bilirubin ≤1.5×ULN*, transaminase <2.5×ULN*, creatinine ≤1.5×ULN*,or creatinine clearance rate ≥45ml/min. ULR: Upper Limit Of Normal.
  • Sign the informed consent form; Compliance is good, can be followed up, willing to comply with the requirements of the study

Who cannot join

  • ECOG Performance Scores > 2 points
  • Organic disease (heart, liver, kidney disease etc), Active infection Organ transplantation immunosuppressive therapy, not capable to complete 4 - 6 cycles of paclitaxel / carboplatin chemotherapy.
  • Any other tumor history not cured in 3 years before this trial.
  • Bone marrow function or organs function not eligible for chemotherapy.
  • Diabetic patients currently receiving the standard anti- diabetes treatment.

Trial locations and contacts

1 site in 1 country.

China1 site

  • Sun Yat-sen University Cancer Center

    Guangzhou, Guangdong, 510060

Other trials in China

About this study

Official title: A Clinical Experience Trial to Detect the Plasma Paclitaxel Drug Concentration in Chinese Non -Small Cell Lung Cancer (NSCLC) Patients Treated With a Paclitaxel Plus Carboplatin (TC) Regimens, and Explore Individualized Treatment Using Pharmacokinetically-guided Dosing Strategy

By detecting the blood concentration of paclitaxel (PTX), Investigator assume this research can identify the individual differences of PTX pharmacokinetics (PK) parameters (TC>0.05 refers to the duration of paclitaxel plasma concentration above 0.05 µmol/L) in Chinese non-small cell lung cancer (NSCLC) patients, and find the correlation between PK results and PTX toxicities and Effectiveness, acquire the optimization method of PTX, and finally try to explore the individualized PTX pharmacokinetically-guided dosing strategy. Orally administer rosiglitazone, which is a substrate of CYP2C8 the same as paclitaxel, before chemotherapy injection. Detect the blood concentration of rosiglitazone, analyze the correlation of rosiglitazone pharmacokinetic parameter and paclitaxel exposure, and explore the effect of rosiglitazone as an in vivo probe of paclitaxel exposure.

  1. The variability of paclitaxel concentrations in the patient population dosed by body surface area (BSA), and the limitation of BSA-based dosing of paclitaxel.
  2. Verify that paclitaxel TC>0.05 is the most relevant predictor of haematological toxicity and clinical outcomes.
  3. Define a dosing algorithm based on paclitaxel TC>0.05 of paclitaxel and quantify its effect on both reducing toxicity and improving Effectiveness.
  4. The effect of using dose modification and administration of G-CSF based on toxicity determined by paclitaxel TC>0.05 measurement.
  5. Construct a trial outline with the aim of reducing grade 4 neutropenia toxicity and ensuring the clinical outcome by using individual dose adjustments based on the dosing algorithm.
  6. Detect the blood concentration of rosiglitazone after orally administration, explore the effect of rosiglitazone as an in vivo probe of paclitaxel exposure based on CYP2C8 activity. Attempt to establish a model to predict the paclitaxel exposure of patients base on rosiglitazone blood concentration before chemotherapy.
Read the detailed description

Rosiglitazone probe:

Rosiglitazone: time point - at least 20 hours before the initiation of chemotherapy, orally administrate 2mg rosiglitazone.

Only before the first cycle chemotherapy.

Chemotherapy regimen:

Paclitaxel: 175mg/m2, d1; Intravenous drip injection with 500ml N.S Carboplatin: AUC=5, d1; Intravenous drip injection with 500ml G.S Paclitaxel injection at first, followed with Carboplatin injection. 21 days per cycle; 6 cycles in total.

Blood samples collection design:

  1. Rosiglitazone blood sample: Only one blood sample before 1st cycle:
  • Sample collected 3 hours after orally administration of rosiglitazone, with EDTA blood tube, at least 4ml;
  1. Paclitaxel blood samples:

Two blood samples per cycle:

  • Sample collected before PTX, with EDTA blood tube, at least 2ml;
  • Sample collected 24 hours after the initiation of PTX, with EDTA blood tube, at least 2ml;

Primary Objective:

Object response rate (ORR): assess the ORR of paclitaxel/carboplatin chemotherapy according to Response Evaluation Criteria In Solid Tumors (RECIST) v1.1, and analyze the relationship of paclitaxel TC>0.05 and ORR.

Secondary Objectives:

Pharmacokinetic parameters: detect the blood concentration of paclitaxel 24 hours after the initiation, and the blood concentration of rosiglitazone 3 hours after orally administration of rosiglitazone. Calculate paclitaxel TC>0.05 and analyze the correlation of rosiglitazone concentration and paclitaxel TC>0.05.

Toxicities rate: assess the toxicities rate and severity of paclitaxel/carboplatin chemotherapy according to Common Terminology Criteria For Adverse Events (CTCAE) v4.03, and analyze the relationship of paclitaxel TC>0.05 and toxicities.

Survival Effectiveness: assess the progression free survival (PFS) and overall survival (OS) of paclitaxel/carboplatin chemotherapy, analyze the relationship of paclitaxel TC>0.05 and survival Effectiveness.

A single arm, phase II, monocentric, clinical experience trial. The eligible patients sign a informed consent form, and receive a 4 - 6 cycles of paclitaxel/carboplatin chemotherapy. Objective response rate is evaluated by imaging examination (CT or MR scan) every 2 cycles. Toxicities are evaluated by patients' diary for toxicity reports and physician's evaluation at day 10 and day 21 at every cycle. Blood samples are collected every cycle. And survival information is collected by clinic and telephone follow-up.

Response follow-up: An imaging examination should be performed in 4weeks before treatment initiation, and patients are going to receive (CT or MR scan) every 2 cycles during the treatment, the methods should be identical with baseline.

Toxicities follow-up: record the toxicities incident and grades from the first cycle to last cycle until the toxicities relieve or stabilize.

Survival follow-up: after treatment discontinuation, PFS is recorded by imaging examination every 2 cycles (8 weeks) until tumor progression, other anti-cancer treatment start, trial ends or death. OS is recorded by clinic follow-up or telephone follow-up until death.

Being tested
Paclitaxel and Carboplatin regimen
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Paclitaxel and Carboplatin regimenDrug

    Also called treatment group

    Chemotherapy regimen:Paclitaxel: 175mg/m2, d1; Intravenous drip injection with 500ml N.S；Carboplatin: AUC=5, d1; Intravenous drip injection with 500ml G.S Paclitaxel injection at first, followed with Carboplatin injection.

Study groups in NCT02737709
Study groupRoleWhat they receive
Paclitaxel and Carboplatin regimenExperimentalPaclitaxel: 175mg/m2, d1; Intravenous drip injection with 500ml N.S Carboplatin: AUC=5, d1; Intravenous drip injection with 500ml G.S Paclitaxel injection at first, followed with Carboplatin injection. 21 days per cycle; 6 cycles in total.
Receives: Drug: Paclitaxel and Carboplatin regimen

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change of tumor sizes from baseline

    Object response rate (ORR): assess the ORR of paclitaxel/carboplatin chemotherapy according to Response Evaluation Criteria In Solid Tumors (RECIST) v1.1

    Measured: baseline; 6 weeks; 12 weeks; 18 weeks; 24 weeks; 32 weeks; up to 3 years.

Secondary outcomes (5)

  1. Area under the plasma concentration versus time curve (AUC) of rosiglitazone

    Detect the plasma concentration of rosiglitazone 3 hours after orally administration of rosiglitazone.

    Measured: 3 hours after rosiglitazone administration

  2. The duration of paclitaxel plasma concentration above 0.05 µmol/L (TC>0.05)

    Detect the blood concentration of paclitaxel 24 hours after the initiation, Calculate paclitaxel TC>0.05

    Measured: 5min before paclitaxel administration; and 24 hours after.

  3. Toxicities rate

    Toxicities rate: assess the toxicities rate and severity of paclitaxel/carboplatin chemotherapy according to Common Terminology Criteria For Adverse Events (CTCAE) v4.03, and analyze the relationship of paclitaxel TC>0.05 and toxicities.

    Measured: day10, day21, day 31, day 42, day 52, day 63, day 73, day 84, day 94, day 105, day115 and day 126.

  4. progression free survival (months)

    Survival Effectiveness: assess the progression free survival (PFS) of paclitaxel/carboplatin chemotherapy

    Measured: From date of consent form until the date of first documented progression, up to 36 months.

  5. Overall survival (months)

    Survival Effectiveness: assess the overall survival (OS) of paclitaxel/carboplatin chemotherapy

    Measured: From date of consent form until the date of death from any cause, up to 36 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Apr 2016 (estimated)
  2. Study startMar 2016
  3. Primary completion25 Oct 2018
  4. Study completion25 Oct 2018

Why it stopped: The study have difficulty in recruiting subjectes

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
51 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02737709
Sponsor's protocol ID
CA139-703
Status last verified
Oct 2018
First submitted
22 Mar 2016
Last updated
29 Oct 2018
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Undecided

Publications

  • Huizing MT, Keung AC, Rosing H, van der Kuij V, ten Bokkel Huinink WW, Mandjes IM, Dubbelman AC, Pinedo HM, Beijnen JH. Pharmacokinetics of paclitaxel and metabolites in a randomized comparative study in platinum-pretreated ovarian cancer patients. J Clin Oncol. 1993 Nov;11(11):2127-35. doi: 10.1200/JCO.1993.11.11.2127.

    PubMed 7901342

  • Kumar N. Taxol-induced polymerization of purified tubulin. Mechanism of action. J Biol Chem. 1981 Oct 25;256(20):10435-41.

    PubMed 6116707

  • Sarosy G, Reed E. Taxol dose intensification and its clinical implications. J Natl Med Assoc. 1993 Jun;85(6):427-31.

    PubMed 8103561

  • Huizing MT, Giaccone G, van Warmerdam LJ, Rosing H, Bakker PJ, Vermorken JB, Postmus PE, van Zandwijk N, Koolen MG, ten Bokkel Huinink WW, van der Vijgh WJ, Bierhorst FJ, Lai A, Dalesio O, Pinedo HM, Veenhof CH, Beijnen JH. Pharmacokinetics of paclitaxel and carboplatin in a dose-escalating and dose-sequencing study in patients with non-small-cell lung cancer. The European Cancer Centre. J Clin Oncol. 1997 Jan;15(1):317-29. doi: 10.1200/JCO.1997.15.1.317.

    PubMed 8996159

  • Joerger M, Huitema AD, Richel DJ, Dittrich C, Pavlidis N, Briasoulis E, Vermorken JB, Strocchi E, Martoni A, Sorio R, Sleeboom HP, Izquierdo MA, Jodrell DI, Calvert H, Boddy AV, Hollema H, Fety R, Van der Vijgh WJ, Hempel G, Chatelut E, Karlsson M, Wilkins J, Tranchand B, Schrijvers AH, Twelves C, Beijnen JH, Schellens JH. Population pharmacokinetics and pharmacodynamics of paclitaxel and carboplatin in ovarian cancer patients: a study by the European organization for research and treatment of cancer-pharmacology and molecular mechanisms group and new drug development group. Clin Cancer Res. 2007 Nov 1;13(21):6410-8. doi: 10.1158/1078-0432.CCR-07-0064.

    PubMed 17975154

  • Miller AA, Rosner GL, Egorin MJ, Hollis D, Lichtman SM, Ratain MJ. Prospective evaluation of body surface area as a determinant of paclitaxel pharmacokinetics and pharmacodynamics in women with solid tumors: Cancer and Leukemia Group B Study 9763. Clin Cancer Res. 2004 Dec 15;10(24):8325-31. doi: 10.1158/1078-0432.CCR-04-1078.

    PubMed 15623609

  • Gianni L, Kearns CM, Giani A, Capri G, Vigano L, Lacatelli A, Bonadonna G, Egorin MJ. Nonlinear pharmacokinetics and metabolism of paclitaxel and its pharmacokinetic/pharmacodynamic relationships in humans. J Clin Oncol. 1995 Jan;13(1):180-90. doi: 10.1200/JCO.1995.13.1.180.

    PubMed 7799018

  • Nakajima M, Fujiki Y, Kyo S, Kanaya T, Nakamura M, Maida Y, Tanaka M, Inoue M, Yokoi T. Pharmacokinetics of paclitaxel in ovarian cancer patients and genetic polymorphisms of CYP2C8, CYP3A4, and MDR1. J Clin Pharmacol. 2005 Jun;45(6):674-82. doi: 10.1177/0091270005276204.

    PubMed 15901749

  • Mould DR, Fleming GF, Darcy KM, Spriggs D. Population analysis of a 24-h paclitaxel infusion in advanced endometrial cancer: a gynaecological oncology group study. Br J Clin Pharmacol. 2006 Jul;62(1):56-70. doi: 10.1111/j.1365-2125.2006.02718.x.

    PubMed 16842379

  • Kobayashi M, Oba K, Sakamoto J, Kondo K, Nagata N, Okabayashi T, Namikawa T, Hanazaki K. Pharmacokinetic study of weekly administration dose of paclitaxel in patients with advanced or recurrent gastric cancer in Japan. Gastric Cancer. 2007;10(1):52-7. doi: 10.1007/s10120-006-0411-6. Epub 2007 Feb 23.

    PubMed 17334719

  • Jiko M, Yano I, Sato E, Takahashi K, Motohashi H, Masuda S, Okuda M, Ito N, Nakamura E, Segawa T, Kamoto T, Ogawa O, Inui K. Pharmacokinetics and pharmacodynamics of paclitaxel with carboplatin or gemcitabine, and effects of CYP3A5 and MDR1 polymorphisms in patients with urogenital cancers. Int J Clin Oncol. 2007 Aug;12(4):284-90. doi: 10.1007/s10147-007-0681-y. Epub 2007 Aug 20.

    PubMed 17701008

  • Ohtsu T, Sasaki Y, Tamura T, Miyata Y, Nakanomyo H, Nishiwaki Y, Saijo N. Clinical pharmacokinetics and pharmacodynamics of paclitaxel: a 3-hour infusion versus a 24-hour infusion. Clin Cancer Res. 1995 Jun;1(6):599-606.

    PubMed 9816021

  • Spratlin J, Sawyer MB. Pharmacogenetics of paclitaxel metabolism. Crit Rev Oncol Hematol. 2007 Mar;61(3):222-9. doi: 10.1016/j.critrevonc.2006.09.006. Epub 2006 Nov 7.

    PubMed 17092739

  • Mielke S, Sparreboom A, Steinberg SM, Gelderblom H, Unger C, Behringer D, Mross K. Association of Paclitaxel pharmacokinetics with the development of peripheral neuropathy in patients with advanced cancer. Clin Cancer Res. 2005 Jul 1;11(13):4843-50. doi: 10.1158/1078-0432.CCR-05-0298.

    PubMed 16000582

  • Augusto C, Pietro M, Cinzia M, Sergio C, Sara C, Luca G, Scaioli V. Peripheral neuropathy due to paclitaxel: study of the temporal relationships between the therapeutic schedule and the clinical quantitative score (QST) and comparison with neurophysiological findings. J Neurooncol. 2008 Jan;86(1):89-99. doi: 10.1007/s11060-007-9438-8. Epub 2007 Jul 5.

    PubMed 17611715

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Paclitaxel and Carboplatin regimen in people with Non-small Cell Lung Cancer, run by Sun Yat-sen University at 1 site in China.

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 8 inclusion and 5 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: stopped early, as of the sponsor's last update on 29 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. 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?

The study was stopped early (reason given: The study have difficulty in recruiting subjectes). Results are not available in the source record.

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?

Change of tumor sizes from baseline (time frame: baseline; 6 weeks; 12 weeks; 18 weeks; 24 weeks; 32 weeks; up to 3 years.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02737709, which also lists 27 linked publications.

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 29 Oct 2018.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in