Study Of CP-751,871 In Combination With Cisplatin And Gemcitabine In Chemotherapy-Naïve Patients With Advanced Non-Small Cell Lung Cancer

Carcinoma, Non-Small-Cell Lung Clinical Trial

Official title:

Phase 1, Dose Escalation Study Of CP-751,871 In Combination With Cisplatin And Gemcitabine In Previously Untreated Patients With Advanced Non-Small Cell Lung Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00560573
• Other study ID #: A4021015
• Status: Completed
• Phase: Phase 1
• First received: November 15, 2007
• Last updated: March 15, 2013
• Start date: November 2007
• Est. completion date: March 2010

Study information

• Verified date: March 2013
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

CP 751,871 is a fully human monoclonal antibody against the Insulin-Like Growth Factor 1 Receptor (IGF-1R). Preclinical and clinical data indicate that CP 751,871 augments the anti-tumor activity of chemotherapy. This study will identify the Maximal Tolerated Dose of CP 751,871 (or the Maximal Feasible Dose) in combination with standard gemcitabine-cisplatin chemotherapy for the treatment of advanced Non-Small Cell Lung cancer.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: March 2010
• Est. primary completion date: June 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically proven diagnosis of Stage IIIB (N3 and/or T4) or Stage IV Non-Small Cell Lung Cancer in patients 18-year-old or older, with Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 not amenable to curative surgery or radiation therapy and an adequate organ function (bone marrow, hepatic, renal, and cardiac) within 14 days prior to enrollment.

Exclusion Criteria:

• Any prior treatment for Non-Small Cell Lung Cancer including chemotherapy, biologic response modifiers or therapy with any investigational agents.

• Patients with known brain metastases, spinal cord compression, uncontrolled superior vein cava syndrome or carcinomatous meningitis.

• Patients with gastrointestinal abnormalities including active gastrointestinal bleeding, pre-diabetes (pre-fasting glycemia > 120 g/dL and/or glycosylate haemoglobin level > 7.5%), known HIV or AIDS-related illness, significant active cardiac disease or receiving chronic steroid therapy or concurrent use of growth hormones or growth hormone inhibitors or aminoglycoside antibiotics should be excluded from the study.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• CP-751,871
CP-751,871 at doses ranging from 6 to 20 mg/Kg on Day 1 of each 21-day cycle. CP-751,871 may be administered even after active comparators discontinuation, for a total number of 17 cycles (1 year).
• Cisplatin
Cisplatin 75* mg/m2 or 80* mg/m2, IV on Day 1 of each 21-day cycle up to 6 cycles. * 75 mg/m2 when in combination with pemetrexed, 80 mg/m2 when in combination with gemcitabine
• Gemcitabine
Gemcitabine 1250 mg/m2, IV on Days 1 and 8 of each 21-day cycle up to 6 cycles
• Pemetrexed
Pemetrexed 500 mg/m2, IV on Day 1 of each 21-day cycle up to 6 cycle

Locations

Country	Name	City	State
Belgium	Pfizer Investigational Site	Charleroi
Ireland	Pfizer Investigational Site	Dublin
Spain	Pfizer Investigational Site	Madrid
Spain	Pfizer Investigational Site	Sevilla

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

Belgium,  Ireland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Maximum Tolerated Dose (MTD)	The MTD was defined as the highest dose level below the maximum administered dose which caused 0 or 1 out of 6 participants to experience a DLT in that given cohort at Cycle 1	Cycle 1, up to Day 21	Yes
Other	Recommended Phase 2 Dose (RP2D)	The RP2D was determined after review and discussion by sponsor and investigators of the study data. Consideration was given to type and severity of toxicity as well as clinical suitability for long-term administration	Baseline to end of dose escalation, which was assessed in the last participant of the dose escalation portion of the study in Month 19	Yes
Primary	Number of Participants With Dose-limiting Toxicities (DLT)	Cycle 1 figitumumab attributed: Grade (Gr) 4 neutropenia (absolute neutrophil count <500 cells/cubic millimeter [mm^3]) >=7 days, febrile neutropenia (Gr 3, fever >=38.5 degrees Celsius), neutropenic infection (Gr 3 neutropenia, infection); Gr 4 thrombocytopenia (platelet <25,000 cells/mm^3), Gr 3 thrombocytopenia >=7 days/bleeding; other Gr 3 not blood/bone marrow Common Terminology Criteria for Adverse Events bar gastrointestinal toxicity, treatment-managed hyperglycemia/fatigue, hypersensitivity; Gr 3-4 hyperglycemia despite treatment; fail to adequately recover to continue study treatment	Start of treatment up to end of Cycle 1, Day 21	Yes
Secondary	Concentration at the End of Infusion (Cinf) for Figitumumab	Figitumumab pharmacokinetic (PK) data was analyzed using noncompartmental methods	Cycle 1 for dose escalation and Cycle 4 for dose expansion	No
Secondary	Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Figitumumab	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). Figitumumab PK data was analyzed using noncompartmental methods	0 (pre-dose), 1, 24, 72, 168, 336, 504 hr in Cycle 1 for dose escation and 0 (pre-dose), 1, 24, 72, 168, 336, 504 hr in Cycle 4 for expansion	No
Secondary	Minimum Observed Plasma Trough Concentration (Cmin) for Figitumumab	Concentration at the end of Cycle 4	0 (pre-dose) in Cycle 5 Day 1	No
Secondary	Maximum Observed Plasma Concentration (Cmax) for Cisplatin	Cisplatin PK data was analyzed using noncompartmental methods. Plasma exposure parameters for cisplatin were analyzed in the absence (Cycle 1) and presence of (Cycle 2) figitumumab	0 (pre-dose), 1.917, 2.5, 3, 4, 5, 24 hr on Cycle 1, Day 1 and Cycle 2, Day 1 for cisplatin 75 mg/m^2 and 0 (pre-dose), 0.917, 1.5, 2, 3, 4, 23 hr on Cycle 1, Day 1 and Cycle 2, Day 1 for cisplatin 80 mg/m^2	No
Secondary	Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Cisplatin	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). Cisplatin PK data was analyzed using noncompartmental methods. Plasma exposure parameters for cisplatin were analyzed in the absence (Cycle 1) and presence (Cycle 2) of figitumumab	0 (pre-dose), 1.917, 2.5, 3, 4, 5, 24 hr on Cycle 1, Day 1 and Cycle 2, Day 1 for cisplatin 75 mg/m^2 and 0 (pre-dose), 0.917, 1.5, 2, 3, 4, 23 hr on Cycle 1, Day 1 and Cycle 2, Day 1 for cisplatin 80 mg/m^2	No
Secondary	Maximum Observed Plasma Concentration (Cmax) for Gemcitabine	Gemcitabine PK data was analyzed using noncompartmental methods. Plasma exposure parameters for gemcitabine were analyzed in the absence (Cycle) 1 and presence (Cycle 2) of figitumumab	0 (pre-dose), 0.417, 1, 1.5, 2.5, 3.5 hr on Cycle 1, Day 1 and Cycle 2, Day 8	No
Secondary	Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Gemcitabine	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). Gemcitabine PK data was analyzed using noncompartmental methods. Plasma exposure parameters for gemcitabine were analyzed in the absence (Cycle 1) and presence (Cycle 2) of figitumumab	0 (pre-dose), 0.417, 1, 1.5, 2.5, 3.5 hr on Cycle 1, Day 1 and Cycle 2, Day 8	No
Secondary	Maximum Observed Plasma Concentration (Cmax) for Pemetrexed	Pemetrexed PK data was analyzed using noncompartmental methods. Plasma exposure parameters for pemetrexed were analyzed in the absence (Cycle 1) and presence (Cycle 2) of figitumumab	0, 0.167, 1.167, 2.167, 4.167, 6.167, 24.167 hr on Cycle 1, Day 1 and Cycle 2, Day 1 for pemetrexed 500 mg/m^2	No
Secondary	Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Pemetrexed	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). Pemetrexed PK data was analyzed using noncompartmental methods. Plasma exposure parameters for pemetrexed were analyzed in the absence (Cycle 1) and presence (Cycle 2) of figitumumab	0, 0.167, 1.167, 2.167, 4.167, 6.167, 24.167 hr on Cycle 1, Day 1 and Cycle 2, Day 1 for pemetrexed 500 mg/m^2	No
Secondary	Percentage of Participants With Objective Response or Prolonged Stabilization	Percentage of participants with a confirmed complete response (CR), confirmed partial response (PR), or stable disease (SD) for at least 12 weeks on study according to Response Evaluation Criteria in Solid Tumors (RECIST). Participants with non measurable disease were considered having a clinical benefit response only in the case of achievement of CR. Participants who developed early progressive disease post dosing and prior to response evaluation were considered to have progressed on study. Confirmed responses were those that persisted on repeat imaging >= 4 weeks after initial response	Screening, from Cycle 2 onwards computerized tomography (CT) scan done within 7-10 days prior to next cycle (approximately Day 15 of each cycle), follow-up (30 days after last study treatment dose)	No
Secondary	Progression-Free Survival (PFS)	Time from the date of enrollment to date of documented disease progression, or death due to any cause	Screening, from Cycle 2 onwards CT scan done within 7-10 days prior to next cycle (approximately Day 15 of each cycle), follow-up (30 days after last study treatment dose)	No
Secondary	Duration of Response (DR)	For responding patients (CR and PR): Time from the date that CR or PR was first recorded to the date of the first documentation of progression	Screening, from Cycle 2 onwards CT scan done within 7-10 days prior to next cycle (approximately Day 15 of each cycle), follow-up (30 days after last study treatment dose)	No
Secondary	Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab	Percentage of participants with positive total or neutralizing anti-drug antibody (ADA) for figitumumab	30 min prior to figitumumab infusion in Cycle 1 and Cycle 4, end of study, fourth follow up visit (approximately 150 days after last dose)	No
Secondary	Serum Total Circulating Insulin-like Growth Factor (IGF-1) Levels	To monitor serum total IGF-1 levels as a potential pharmacodynamic response to figitumumab treatment	Baseline, Day 8, end of study	No

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