Carboplatin And Paclitaxel With Or Without CP-751, 871 (An IGF-1R Inhibitor) For Advanced NSCLC Of Squamous, Large Cell And Adenosquamous Carcinoma Histology

The study was discontinued on December 29, 2009 due to an analysis by an independent Data Safety Monitoring Committee indicating that the addition of CP-751,871 \[figitumumab\] to paclitaxel plus carboplatin would be unlikely to meet the primary endpoint of improving overall survival compared to paclitaxel plus carboplatin alone. The DSMC recommendation to terminate the trial was based on futility, not on specific safety concerns; however, the DSMC recommended to investigate hyperglycemia as a potential contributor to the morbidity of the patients.

• CP-751,871 (Figitumumab) (Drug): CP 751,871 is a potent and selective fully human monoclonal antibody against the insulin like growth factor 1 receptor (IGF-1R). Patients in Arm A will receive CP-751, 871 intravenously every 21 days for up to six cycles.
• Carboplatin (Drug): Carboplatin is a standard chemotherapeutic agent used in patients with lung cancer. Patients in Arm A will receive carboplatin intravenously every 21 days for up to six cycles.
• Paclitaxel (Drug): Paclitaxel is a standard chemotherapeutic agent used in patients with lung cancer. Patients in Arm A will receive paclitaxel intravenously every 21 days for up to six cycles.
• Carboplatin (Drug): Carboplatin is a standard chemotherapeutic agent used in patients with lung cancer. Patient in Arm B will receive carboplatin intravenously every 21 days for up to six cycles.
• Paclitaxel (Drug): Paclitaxel is a standard chemotherapeutic agent used in patients with lung cancer. Patient in Arm B will receive paclitaxel intravenously every 21 days for up to six cycles.

Primary outcomes

• Overall Survival (OS) [Baseline until death, assessed monthly after end of treatment, up to 30 months]: Overall survival was the duration from randomization to death. For participants who are alive, overall survival was censored at the last contact.

Secondary outcomes

• Progression-Free Survival (PFS) [At baseline, every 6 weeks until radiological disease progression or the participant begins a subsequent anticancer therapy, up to 22.7 months.]: PFS was defined as the time from randomization to first progression or death due to any cause, whichever came first. Participants last known to be alive and progression-free, with baseline and >=1 on-study assessment, were censored at last disease assessment verifying lack of progression. Progression was determined by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 (20% increase in the sum of target lesions' longest diameter over nadir, unequivocal progression of non-target disease, or appearance of new lesions).
• Percentage of Participants With Objective Response (OR) [At baseline, every 6 weeks until radiological disease progression has been documented or the participant begins a subsequent anticancer therapy, up to 22.7 months]: Percentage of participants with OR based on assessment of confirmed complete response (CR) or confirmed partial response(PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR defined as complete disappearance of all target lesions and non-target disease. No new lesons. PR defined as ≥30% decrease under baseline of the sum of diameters of all target lesions. No unequivocal progression of non-target disease. No new lesions.
• European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC QLQ-C30) [Day 1 of every cycle (3-week cycle), every 3 weeks during maintenance phase and at the End of Treatment Visit, assessed up to 37.4 months]: EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4 point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale (1 'very poor' to 7 'Excellent'). Scores averaged, transformed to 0-100 scale; higher score=better level of functioning or greater degree of symptoms.
• European Organization for Research and Treatment of Cancer (EORTC), Quality of Life Questionnaire-Lung Cancer 13 (QLQ- LC13) Score [Day 1 of every cycle (3-week cycle), every 3 weeks during maintenance phase and at the End of Treatment Visit, assessed up to 37.4 months]: QLQ-LC13 consisted of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy. The 13 questions comprised 1 multi-item scale for dyspnea and 10 single-item symptoms and side effects (coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, chest pain, arm pain, other pain, and medicine for pain). Recall period: past week; response range: not at all to very much. Scale score range: 0 to 100. Higher symptom score = greater degree of symptoms.
• Euro Quality of Life (EQ-5D)- Health State Profile Utility Score [Day 1 of every cycle (3-weeks cycle), every 3 weeks during maintenance phase and at the End of Treatment Visit, assessed up to 37.4 months]: EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state ("confined to bed"). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range of -0.594 to 1; higher score indicates a better health state.
• Maximum Observed Plasma Concentration (Cmax) for Figitumumab [Cycle 1, Day 1 (predose and 1 hour after end of infusion); Day 1 of Cycles 2, 4, 6 (predose); Cycle 5 Day 1 (predose, 1 hour after end of infusion); 28 days and 150 days after the last figi dose]
• Minimum Observed Plasma Trough Concentration (Cmin)for Figitumumab [Cycle 1, Day 1 (predose and 1 hour after end of infusion); Day 1 of Cycles 2, 4, 6 (predose); Cycle 5 Day 1 (predose, 1 hour after end of infusion); 28 days and 150 days after the last figi dose]
• Number of Participants With Total Anti-drug Antibodies (ADA) [Cycles 1, 2, and 4 (predose); 28 days and 150 days after the last figi dose]: ADAs are immunogenicity indicators to figitumumab. Participants reporting positive for ADAs are indicated by an endpoint titer of no less than 6.64.
• Change From Baseline in Serum Insulin Growth Factor 1 (IGF1) Levels [Cycles 1 and 4 (predose) and at end of treatment]

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Confirmed diagnosis of non small cell lung cancer with a primary histology of predominantly squamous cell, large cell or adenosquamous carcinoma.
* Advanced NSCLC with documented Stage IIIB (with pleural effusion) or Stage IV or recurrent disease.
* No prior systemic treatment for NSCLC, except for adjuvant chemotherapy. Adjuvant chemotherapy must have completed for greater than or equal to 12 months prior to randomization.
* Prior surgery or radiation therapy is permitted if completed at least 3 weeks prior to randomization and all acute toxicities have resolved.
* ECOG performance status (PS) 0 or 1.

Exclusion Criteria:

* Patients with symptomatic central nervous system (CNS) metastases are not permitted.
* Patients requiring chronic steroid use or patients with uncontrolled diabetes are not permitted.
* Patients with other active cancer types are not permitted.

Participant flow

Outcome results

• Overall Survival (OS) (Primary), Median, months: Figitumumab + Paclitaxel and Carboplatin 8.6 (7.4 to 9.3); Paclitaxel and Carboplatin (Chemo) 9.8 (8.6 to 10.9) (p 0.064)
• Progression-Free Survival (PFS) (Secondary), Median, months: Figitumumab + Paclitaxel and Carboplatin 4.7 (4.2 to 5.4); Paclitaxel and Carboplatin (Chemo) 4.6 (4.2 to 5.4) (p 0.270)
• Percentage of Participants With Objective Response (OR) (Secondary), Number, percentage of participants: Figitumumab + Paclitaxel and Carboplatin 33.0 (28.1 to 38.3); Paclitaxel and Carboplatin (Chemo) 34.5 (29.5 to 39.8) (p 0.685)
• European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC QLQ-C30) (Secondary)
• European Organization for Research and Treatment of Cancer (EORTC), Quality of Life Questionnaire-Lung Cancer 13 (QLQ- LC13) Score (Secondary)
• Euro Quality of Life (EQ-5D)- Health State Profile Utility Score (Secondary)
• Maximum Observed Plasma Concentration (Cmax) for Figitumumab (Secondary)
• Minimum Observed Plasma Trough Concentration (Cmin)for Figitumumab (Secondary)
• Number of Participants With Total Anti-drug Antibodies (ADA) (Secondary), Number, participants: Figitumumab + Paclitaxel and Carboplatin 2; Paclitaxel and Carboplatin (Chemo) 0
• Change From Baseline in Serum Insulin Growth Factor 1 (IGF1) Levels (Secondary)

Adverse events

Serious adverse events by term

126 more terms not shown.

Other adverse events by term

Limitations and caveats: The study was terminated early due to futility. CP-751,871 will not undergo further development in the indication of advanced non-adenocarcinoma non-small cell lung cancer (NSCLC).

180 more sites not listed.

• Results publication: Roeland EJ, Fintelmann FJ, Yang R, Tarasenko L, Bonomi PD. Evaluation of Weight Gain and Overall Survival of Men Versus Women With Advanced Non-Small Cell Lung Cancer. J Cachexia Sarcopenia Muscle. 2025 Dec;16(6):e70131. doi: 10.1002/jcsm.70131. PMID 41332393
• Results publication: Roeland EJ, Fintelmann FJ, Hilton F, Yang R, Whalen E, Tarasenko L, Calle RA, Bonomi PD. The relationship between weight gain during chemotherapy and outcomes in patients with advanced non-small cell lung cancer. J Cachexia Sarcopenia Muscle. 2024 Jun;15(3):1030-1040. doi: 10.1002/jcsm.13426. Epub 2024 Mar 11. PMID 38468440
• Results publication: Langer CJ, Novello S, Park K, Krzakowski M, Karp DD, Mok T, Benner RJ, Scranton JR, Olszanski AJ, Jassem J. Randomized, phase III trial of first-line figitumumab in combination with paclitaxel and carboplatin versus paclitaxel and carboplatin alone in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2014 Jul 1;32(19):2059-66. doi: 10.1200/JCO.2013.54.4932. Epub 2014 Jun 2. PMID 24888810

• Pfizer CT.gov Call Center, Study director, Pfizer