Chemotherapy and Radiation in Treating Participants With Stage 3 Non-Small Cell Lung Cancer (PROCLAIM)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00686959
First received: May 28, 2008
Last updated: October 22, 2015
Last verified: October 2015
  Purpose
This study will compare the overall survival of participants with locally-advanced, Stage III Non-Small Cell Lung Cancer (NSCLC) with nonsquamous cell histology.

Condition Intervention Phase
Non Small Cell Lung Cancer
Drug: Pemetrexed
Drug: Cisplatin
Drug: Etoposide
Drug: Vinorelbine
Drug: Paclitaxel
Drug: Carboplatin
Radiation: Thoracic Radiation Therapy (TRT)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 3 Study of Pemetrexed, Cisplatin, and Radiotherapy Followed by Consolidation Pemetrexed Versus Etoposide, Cisplatin, and Radiotherapy Followed by Consolidation Cytotoxic Chemotherapy of Choice in Patients With Unresectable, Locally Advanced, Stage III Non-Small Cell Lung Cancer Other Than Predominantly Squamous Cell Histology

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Overall Survival [ Time Frame: Baseline to date of death from any cause ] [ Designated as safety issue: No ]
    Overall survival (OS) time is defined as the time from the date of randomization to the date of death from any cause. For participants not known to have died as of the data cut-off date, OS time was censored at the last contact date the participant was known to be alive prior to the data cut-off date. OS was summarized using Kaplan-Meier estimates.


Secondary Outcome Measures:
  • Progression-free Survival (PFS) [ Time Frame: Baseline to measured progressive disease or death from any cause ] [ Designated as safety issue: No ]
    Progression-free survival (PFS) time is defined as the time from the date of randomization to the first date of documented objective progressive disease (PD) or death from any cause. For participants who were not known to have died or to have had objective PD as of the data inclusion cut-off date for a particular analysis, PFS was censored at the date of the last objective progression-free disease assessments. For participants who took any subsequent systemic anticancer therapy prior to progression or death, PFS was censored at the date of the last objective progression-free disease assessment prior to the start date of any subsequent systemic anticancer therapy. PFS time was summarized using Kaplan-Meier estimates.

  • Objective Response Rate (Complete Response [CR] + Partial Response [PR]) [ Time Frame: Baseline to measured progressive disease ] [ Designated as safety issue: No ]
    Overall response rate (ORR) is the best response of CR or PR as classified by the investigators according to the Response Evaluation Criteria in Solid Tumors (RECIST, v1.1) guidelines. CR is defined as the disappearance of all target and non-target lesions, normalization of tumor marker level of non-target lesions, and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter (mm). PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants with at least 1 measurable lesion, multiplied by 100.

  • Survival Rates at 1-, 2-, and 3-years [ Time Frame: Baseline to date of death from any cause ] [ Designated as safety issue: Yes ]
    The probability that survival time is at least 1-, 2-, or 3- years was summarized using Kaplan-Meier estimates.

  • First Site of Disease Failure in Terms of Relapse [ Time Frame: Baseline to relapse ] [ Designated as safety issue: No ]
    The percentage of participants with first sites of disease failure in terms of relapse within the radiation treatment field, inside the thorax, (outside of the radiation field), or distant disease are presented. Results were summarized using Kaplan-Meier estimates. Some participants relapsed in more than 1 location/site and appear in more than a single category.

  • Percentage of Participants With a Post Baseline Swallowing Diary Score >=4 [ Time Frame: Baseline through 30 days post study ] [ Designated as safety issue: No ]
    Participants were provided with a swallowing diary to record issues with swallowing using a 5-point categorical scale: (1) no problems; (2) mild soreness; (3) swallowing solids with some difficulty; (4) inability to swallow solids; and (5) inability to swallow liquids. Participants rated swallowing over the previous 24 hours. The percentage of participants was calculated by dividing the number of with a post baseline swallowing diary score >=4 by total number of participants analyzed, multiplied by 100. No adjustments were made for the number of available assessments nor were any interpolation of missing assessments made.


Other Outcome Measures:
  • Adverse Events: The Number of Deaths Per Treatment Group [ Time Frame: Baseline through 30 days post study ] [ Designated as safety issue: Yes ]
    The number of deaths that occurred while on study drug, the number of deaths due to adverse events (AEs) while on study drug, and the number of deaths due to the study disease (that is, disease progression) while on study drug are presented. In addition, the number of deaths within 30 days of treatment discontinuation, the number of deaths due to AEs within 30 days of treatment discontinuation, and the number of deaths due to study disease within 30 days of treatment discontinuation are presented. For both the deaths due to AEs that occurred on study and for deaths due to AEs that occurred within 30 days of treatment discontinuation, the causality (events assess as possibly related [poss related] to study drug per investigator judgement) is also presented. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.


Enrollment: 598
Study Start Date: September 2008
Study Completion Date: November 2014
Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A: Pemetrexed + Cisplatin and TRT

Participants were treated with Pemetrexed plus Cisplatin and concurrent thoracic radiation therapy (TRT) ("Concurrent Phase") for three 21-day cycles, followed by a 3-5 week "Recovery Period," then treated with consolidation chemotherapy with pemetrexed ("Consolidation Phase") for up to four 21-day cycles

Concurrent Phase:

Pemetrexed: 500 milligrams per meter squared (mg/m^2), intravenous (IV) on Day 1 of each 21-day cycle for 3 cycles.

Cisplatin: 75 mg/m^2, IV on Day 1 of each 21-day cycle x 3 cycles. TRT: Beginning on Day 1 of chemotherapy, once daily fractions (2 Gray [Gy] per day), 5 days a week for 6 weeks and 3 days to target 66 Gy in 33 fractions.

Consolidation Phase:

Pemetrexed: 500 mg/m^2, IV on Day 1 of each 21-day cycle up to 4 cycles

Drug: Pemetrexed
infusion over 10 minutes
Other Names:
  • Alimta
  • LY231514
Drug: Cisplatin
infusion over 60 minutes with adequate anti-emetic treatment and appropriate hydration per local practice guidelines
Radiation: Thoracic Radiation Therapy (TRT)
Active Comparator: Arm B: Etoposide + Cisplatin and TRT

Participants were treated with Etoposide plus Cisplatin and concurrent TRT ("Concurrent Phase") for two 28-day cycles, followed by a 3-5 week "Recovery Period," then received consolidation treatment with cytotoxic chemotherapy of choice ("Consolidation Phase") for up to 2 cycles

Concurrent Phase:

Etoposide/Cisplatin (28-day cycle); Etoposide: 50 mg/m^2, IV on Days 1 to 5 and Days 29 to 33 and Cisplatin: 50 mg/m^2, IV on Days1, 8, 29, and 36

Consolidation Phase options:

Option 1: Continue the same treatment plan as Concurrent Phase Option 2: Vinorelbine/Cisplatin (21-day cycle); Vinorelbine: 30 mg/m^2, IV on Days 1, 8, 22, and 29; Cisplatin: 75 mg/m^2, IV on Days 1 and 22 Option 3: Paclitaxel/Carboplatin (21-day cycle); Paclitaxel: 200 mg/m^2, IV, on Days 1 and 22; Carboplatin: area under the concentration-time curve (AUC) = 6 (Carboplatin dosing based on calculated creatinine clearance), IV on Days 1 and 22

Drug: Cisplatin
infusion over 60 minutes with adequate anti-emetic treatment and appropriate hydration per local practice guidelines
Drug: Etoposide
administered per local practice guidelines over a minimum of 30 minutes
Drug: Vinorelbine
administered over 6-10 minutes infusion per local practice guidelines
Drug: Paclitaxel
administered as a 3-hour infusion
Drug: Carboplatin
administered per local practice guidelines over 30 minutes
Radiation: Thoracic Radiation Therapy (TRT)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants must have Stage IIIA or IIIIB NSCLC of the non-squamous type
  • Participants must have measureable tumor lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines or disease that can be evaluated on computerized tomography (CT) scan
  • Participants must be physically mobile, take care of themselves and must be up and about and able to perform light activities, such as light housework or office work
  • Participants must be 18 years of age or older
  • Participants must have lost no more than 10% of their body weight in the previous 3 months
  • Women must be sterile, postmenopausal, or on contraception, and men must be sterile or on contraception
  • Participants' test results assessing the function of their blood forming tissue, kidneys, liver, and lungs must be satisfactory
  • Participants with Stage IIIB NSCLC who have supraclavicular nodal involvement may be entered into this study. However, participants with cervical nodes are not permitted. The upper border of supraclavicular nodes must not extend above the upper border of the lateral end of the clavicle, extended medially.

Exclusion Criteria:

  • Participants cannot have other on-going (uncontrolled) illnesses, including active infections, recent heart problems, or psychiatric illnesses
  • Participants who are unable to take vitamins (including injections of vitamin B12) or oral cortisone medication
  • Participants who have had a heart attack (myocardial infarction) or other cardiac issues within 6 months of the trial
  • Participants who have received other investigational drugs within the last 30 days
  • Participants who are unable to stop taking more than 1.3 grams of aspirin on a daily basis or non-steroidal anti-inflammatory agents
  • Participants who have diseases considered for surgical treatment as part of their care plan, such as Pancoast or superior sulcus tumors
  • Participants who had prior thoracic radiation. However, other prior radiotherapy is allowed. Participants must have recovered from the toxic effects of the treatment prior to study enrollment. Participants may not have received whole pelvis radiation or radiation to more than 25% of their bone marrow. Prior radiotherapy must have been completed at least 30 days prior to study treatment.
  • Participants who have a radiation treatment plan that would expose more than 35% of the volume of their lung to 20 gray (Gy) or more of radiation
  • Participants who have concurrent cancer from another primary site requiring treatment of any kind within the past 5 years. Exemptions to this will be permitted on a case-by-case basis after prior approval by the Sponsor physician or designate if the investigator believes the participant's risk of recurrence and death is very low. Curatively treated nonmelanoma skin cancer or in situ carcinoma of any origin is allowed. Participants with recurrence of a previously resected lung cancer or who have a second primary lung cancer are ineligible.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00686959

  Show 133 Study Locations
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
  More Information

Additional Information:
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00686959     History of Changes
Other Study ID Numbers: 11514  H3E-MC-JMIG 
Study First Received: May 28, 2008
Results First Received: October 22, 2015
Last Updated: October 22, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Carboplatin
Cisplatin
Etoposide
Etoposide phosphate
Pemetrexed
Vinorelbine
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Folic Acid Antagonists
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Radiation-Sensitizing Agents
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on May 02, 2016