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NCT00948675

Study of Participants With Advanced Non-Small Cell Lung Cancer

Completed Phase 3 Results posted Last updated 29 October 2021
What this trial tests

Phase 3 trial testing Pemetrexed in Advanced Non-Small Cell Lung Cancer in 361 participants. Completed in 6 November 2020.

Timeline
1 September 2009
Primary endpoint
31 January 2013
6 November 2020

Quick facts

Lead sponsorEli Lilly and Company
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment361
Start date1 September 2009
Primary completion31 January 2013
Estimated completion6 November 2020
Sites45 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Eli Lilly and Company — full company profile →

Who can join

18 and older, any sex, with Advanced Non-Small Cell Lung Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Progression Free Survival Without Grade 4 Toxicity (G4PFS) as Measured by the Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 Primary · Randomization to measured progressive disease or treatment discontinuation up to 39.49 months

G4PFS was defined as the duration from the date of randomization to the earliest occurrence date of one of the following three events: Common Terminology Criteria (CTC) grade 4 adverse events (G4AEs), or progressive disease (PD) or death from any cause, whichever occurred earlier. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. PD is ≥20% increase in sum of longest diameter of target lesions or the appearance of new lesions. For participants who had no G4AEs, or PD, or death at the time of the data inclusion cutoff, PFS was censored at their

GroupValue95% CI
Pemetrexed + Carboplatin3.912.73 – 4.37
Paclitaxel + Carboplatin + Bevacizumab2.862.20 – 4.30
Progression Free Survival (PFS) Secondary · Randomization to measured progressive disease up to 39.49 months

PFS was defined as the duration from the date of randomization to the date of progressive disease (PD) or death from any cause. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. PD was ≥20% increase in sum of longest diameter of target lesions or the appearance of new lesions. For participants who had no PD or death at the time of the data inclusion cutoff, PFS was censored at their last objective progression-free disease assessment prior to the cutoff date or the date of initiation of subsequent systemic anticancer therapy.

GroupValue95% CI
Pemetrexed + Carboplatin4.444.21 – 5.32
Paclitaxel + Carboplatin + Bevacizumab5.455.03 – 5.95
Overall Survival (OS) Secondary · Randomization to date of death from any cause up to 39.49 months

OS was defined as the duration from the date of randomization to the date of death from any cause. For participants who were alive at the time of the data inclusion cutoff, OS was censored at the last date the participant was known to be alive.

GroupValue95% CI
Pemetrexed + Carboplatin10.519.26 – 11.96
Paclitaxel + Carboplatin + Bevacizumab11.669.17 – 14.32
Percentage of Participants With Complete Response or Partial Response (Overall Tumor Response Rate) Secondary · Baseline to date of objective progressive disease up to 39.49 months

Overall Response rate (ORR) was the percentage of participants with a confirmed complete response (CR) or partial response (PR), as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. CR was the disappearance of all target and non-target lesions; PR was a ≥30% decrease in sum of longest diameter of target lesions without new lesion and progression of non-target lesions. ORR was calculated as a total number of participants with CR or PR from the start of study treatment until disease progression or recurrence divided by th

GroupValue95% CI
Pemetrexed + Carboplatin23.617.7 – 30.5
Paclitaxel + Carboplatin + Bevacizumab27.421.0 – 34.5
Disease Control Rates Defined as Complete Response (CR), Partial Response (PR), and Stable Disease (SD) Secondary · Baseline to date of objective progressive disease up to 39.49 months

Disease control rate was the percentage of participants with a confirmed CR, PR or SD, as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. CR was the disappearance of all target and non-target lesions; PR was a ≥30% decrease in sum of longest diameter of target lesions without new lesion and progression of non-target lesion; SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. Disease control rate was calculated as a total number of participants with CR or PR

GroupValue95% CI
Pemetrexed + Carboplatin59.952.4 – 67.1
Paclitaxel + Carboplatin + Bevacizumab57.049.4 – 64.3

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline to Follow-up (up to 9 years). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Pemetrexed + Carboplatin
Serious: 76/171 (44%)
Deaths:
Paclitaxel + Carboplatin + Bevacizumab
Serious: 64/166 (39%)
Deaths:

Serious adverse events (136 terms)

ReactionSystemPemetrexed + CarboplatinPaclitaxel + Carboplatin +…
PneumoniaInfections and infestations
AnaemiaBlood and lymphatic system disorders
DehydrationMetabolism and nutrition disorders
VomitingGastrointestinal disorders
NauseaGastrointestinal disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
DiarrhoeaGastrointestinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
NeutropeniaBlood and lymphatic system disorders
Chest painGeneral disorders
Febrile neutropeniaBlood and lymphatic system disorders
ThrombocytopeniaBlood and lymphatic system disorders
AstheniaGeneral disorders
Renal failure acuteRenal and urinary disorders
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
HypotensionVascular disorders
Atrial flutterCardiac disorders
Cardiac failure congestiveCardiac disorders
Small intestinal obstructionGastrointestinal disorders
Disease progressionGeneral disorders
PainGeneral disorders
Urinary tract infectionInfections and infestations
Haemoglobin decreasedInvestigations
SyncopeNervous system disorders
Other adverse events (68 terms — click to expand)

ReactionSystemPemetrexed + CarboplatinPaclitaxel + Carboplatin +…
FatigueGeneral disorders
NauseaGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
ConstipationGastrointestinal disorders
ThrombocytopeniaBlood and lymphatic system disorders
AlopeciaSkin and subcutaneous tissue disorders
Decreased appetiteMetabolism and nutrition disorders
DiarrhoeaGastrointestinal disorders
VomitingGastrointestinal disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
LeukopeniaBlood and lymphatic system disorders
ArthralgiaMusculoskeletal and connective tissue disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Neuropathy peripheralNervous system disorders
CoughRespiratory, thoracic and mediastinal disorders
InsomniaPsychiatric disorders
Oedema peripheralGeneral disorders
HyperglycaemiaMetabolism and nutrition disorders
Weight decreasedInvestigations
Peripheral sensory neuropathyNervous system disorders
DizzinessNervous system disorders
HypertensionVascular disorders
DysgeusiaNervous system disorders
HeadacheNervous system disorders
HypokalaemiaMetabolism and nutrition disorders
HypomagnesaemiaMetabolism and nutrition disorders
Haemoglobin decreasedInvestigations
DehydrationMetabolism and nutrition disorders
MyalgiaMusculoskeletal and connective tissue disorders
RashSkin and subcutaneous tissue disorders
AstheniaGeneral disorders
Urinary tract infectionInfections and infestations
Neutrophil count decreasedInvestigations
Platelet count decreasedInvestigations
DyspepsiaGastrointestinal disorders
Back painMusculoskeletal and connective tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders
ProteinuriaRenal and urinary disorders
Chest painGeneral disorders

Most-reported serious reactions: Pneumonia, Anaemia, Dehydration, Vomiting, Nausea, Pulmonary embolism, Diarrhoea, Dyspnoea.

Data from ClinicalTrials.gov NCT00948675 adverse events section.

Sponsor's own description

The purpose of this study is to compare the regimens of pemetrexed, carboplatin with pemetrexed maintenance and paclitaxel, carboplatin, bevacizumab with bevacizumab maintenance in participants with Stage IV nonsquamous non-small cell lung cancer.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. PRONOUNCE: randomized, open-label, phase III study of first-line pemetrexed + carboplatin followed by maintenance pemetrexed versus paclitaxel + carboplatin + bevacizumab followed by maintenance bevacizumab in patients ith advanced nonsquamous non-small-cell lung cancer.
    Zinner RG, Obasaju CK, Spigel DR, Weaver RW, et al · · 2015 · cited 130× · PMID 25371077 · DOI 10.1097/jto.0000000000000366
  2. Antiangiogenic agents in combination with chemotherapy in patients with advanced non-small cell lung cancer.
    Ulahannan SV, Brahmer JR. · · 2011 · cited 58× · PMID 21469981 · DOI 10.3109/07357907.2011.554476
  3. Antiangiogenic agents in the management of non-small cell lung cancer: where do we stand now and where are we headed?
    Aggarwal C, Somaiah N, Simon G. · · 2012 · cited 53× · PMID 22481432 · DOI 10.4161/cbt.19594
  4. Maintenance therapy in NSCLC: why? To whom? Which agent?
    Novello S, Milella M, Tiseo M, Banna G, et al · · 2011 · cited 21× · PMID 21548925 · DOI 10.1186/1756-9966-30-50
  5. Role of Gemcitabine and Pemetrexed as Maintenance Therapy in Advanced NSCLC: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
    Hu X, Pu K, Feng X, Wen S, et al · · 2016 · cited 12× · PMID 26954503 · DOI 10.1371/journal.pone.0149247
  6. Targeting angiogenesis in advanced non-small cell lung cancer.
    Lammers PE, Horn L. · · 2013 · cited 12× · PMID 24142825 · DOI 10.6004/jnccn.2013.0146
  7. Identification of cardiotoxicity related to non-small cell lung cancer (NSCLC) treatments: A systematic review.
    Chan SHY, Khatib Y, Webley S, Layton D, et al · · 2023 · cited 10× · PMID 37383708 · DOI 10.3389/fphar.2023.1137983
  8. Combined Immunotherapy with Chemotherapy versus Bevacizumab with Chemotherapy in First-Line Treatment of Driver-Gene-Negative Non-Squamous Non-Small Cell Lung Cancer: An Updated Systematic Review and Network Meta-Analysis.
    Chai Y, Wu X, Bai H, Duan J. · · 2022 · cited 8× · PMID 35329978 · DOI 10.3390/jcm11061655

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