MK-0646 Insulin Growth Factor 1 Receptor Antibody in Stage IIIb or IV Metastatic Non-Squamous Lung Cancer

NCT00799240 | Completed Phase 2 DMC

• 2 other identifiers: 11386MK-0646
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 4

Brief Summary

This study will compare the rate of chemotherapy: pemetrexed and cisplatin compared with the combination of pemetrexed/cisplatin with MK-0646. The other purposes are to determine how long we can control the cancer growth and toxicity and safety of the combination. Laboratory research with the tumor tissue and blood obtained will be done to assess IGF-1R expression and related markers and correlate with response and survival.

Conditions

Non Small Cell Lung Cancer

Keywords

lung cancer; stage IIIb; pleural effusion; stage IV; metastatic lung cancer; non squamous lung cancer; IGF-1R; Pemetrexed; Cisplatin

Outcome Measures

Primary Outcomes (1)

• Compare response rate between the two arms.

  31 months

Secondary Outcomes (2)

• Progression-free survival, overall survival and Toxicity profile

  31 months

• Exploratory Objectives: Assess biomarkers of Pemetrexed, IGF-1R and immunogenicity of MK-0646.

  31 months

Study Arms (2)

Arm A Pemetrexed Cisplatin

ACTIVE COMPARATOR

Arm A: Pemetrexed, cisplatin: pemetrexed and cisplatin chemotherapy at standard doses given IV every 21 days. Patients will be treated for a maximum of 6 cycles.

Drug: Arm A: Pemetrexed Cisplatin

Arm B Permetrexed, Cisplatin, MK-0646

EXPERIMENTAL

Pemetrexed and cisplatin chemotherapy at standard doses given IV every 21 days in combination with MK-0646 given IV, 10 mg/Kg, Days 1, 8 and 15 weekly

Drug: Arm B Pemetrexed, Cisplatin and MK-0646

Interventions

Arm A: Pemetrexed Cisplatin DRUG

Pemetrexed: 500mg/m2 IV on day 1 and Cisplatin: 75 mg/m2 IV on day 1 every 21 days x 6 cycles.

Also known as: MK-0646

Arm A Pemetrexed Cisplatin

Arm B Pemetrexed, Cisplatin and MK-0646 DRUG

Pemetrexed 500 mg/m2 IV on Day 1 and Cisplatin 75 mg/m2 IV on Day 1 every 21 days for 6 cycles in combination with MK-0646 will be given IV, 10 mg/KG, Days 1, 8 and 15 weekly.

Also known as: MK-0646

Arm B Permetrexed, Cisplatin, MK-0646

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• histologically or cytologically proven newly diagnosed Stage IlIB or Stage IV advanced primary non-small cell bronchogenic lung cancer (non-squamous cell to include bronchoalveolar, adenocarcinoma, large cell carcinoma, or unspecified).
• clinically significant pleural effusion must have a thoracentesis.
• Patients with brain metastases are eligible provided they have completed brain radiation, neurologically stable, off dexamethasone for at least 1 week prior to registration. Patients with asymptomatic brain metastatic disease are eligible if they do not require radiation and are neurologically stable without dexamethasone.
• measurable disease documented by CT, MRI, X-ray or physical exam. Measurable disease must be assessed within 28 days prior to registration. Pleural effusions, ascites and laboratory parameters are not acceptable as the only evidence of disease. Non-measurable disease must be assessed within 28 days prior to registration. All disease must be assessed and documented.
• Prior radiation is permitted; at least one week must have elapsed since the completion of prior radiation therapy and must have recovered from all associated toxicities at time of registration. Measurable or non-measurable disease must be outside the previous radiation field or a new lesion must be present.
• At least 4 weeks have elapsed since surgery (thoracic or other major surgeries) and patients have recovered from all associated toxicities at the time of registration. Measurable disease must be present outside the area of surgical resection. There must be no anticipation of need for major surgical procedures during protocol treatment.
• Age ≥ 18 years old.
• ECOG performance status of 0-1.
• adequate bone marrow function defined by platelet count at least 100,000/mm3, hemoglobin ≥ 9g/dl, leukocyte count at least 3,000/mm OR absolute neutrophil count at least 1,500/mm3.
• adequate hepatic function documented by serum bilirubin ≤ 1.5x upper normal limit, AST or ALT, and alkaline phosphatase all ≤ 3 x IULN within 28 days prior to registration. (Except in presence of known hepatic metastasis, wherein AST or ALT may be up to 5 X upper normal limit.)
• serum creatinine ≤ institutional upper limit of normal (IULN) AND calculated or measured creatinine clearance ≥ 50 ml/mm using the Cockcroft Gault Formula. These tests must have been performed within 28 days prior to registration.
• ability to give informed consent.
• Able to provide consent for gene expression profiling, histopathology, and/or immunohistochemical assays
• Women of childbearing potential must have negative serum pregnancy test.
• Patients taking NSAIDs must agree to interrupt NSAIDS 2 days before (5 days for long-acting NSAIDs), the day of, and 2 days following administration of pemetrexed.

You may not qualify if:

• Prior systemic chemotherapy or biologic therapy for non-small cell lung cancer. If neoadjuvant therapy or adjuvant therapy was given, patient must be at least 1 year out from the last chemotherapy and fully recovered from all toxicities.
• Cardiovascular: uncontrolled congestive heart failure, high blood pressure, unstable angina, or myocardial infarction within the prior year,serious cardiac arrhythmias requiring medication.
• Serious uncontrolled active infection, acute hepatitis or known HIV.
• Prior history of severe allergy (grade 3 or 4) to human monoclonal antibody.
• Concurrent use of human growth hormone or growth hormone inhibitors.
• Uncontrolled diabetes mellitus defined as a Hemoglobin A1C≥ 7.
• An other active malignancy in the past 2 years.
• Pregnant or nursing women are not eligible to participate in this trial due to the potential teratogenic or abortifacient effects of the study drug on the fetus or nursing infant. Persons of reproductive potential must have agreed to use two methods of effective contraception prior to, during, and for 4 weeks after study therapy.

Sponsors & Collaborators

• University of Kansas: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (4)

Hutchinson Clinic, PA

Hutchinson, Kansas, 67502, United States

Location

Kansas University Cancer Center

Kansas City, Kansas, 66160, United States

Location

Stormont Vail Healthcare

Topeka, Kansas, 66606, United States

Location

VA Medical Center

Kansas City, Missouri, 64128, United States

Location

Related Publications (1)

• Huang CH, Williamson SK, Neupane P, Taylor SA, Allen A, Smart NJ, Uypeckcuat AM, Spencer S, Wick J, Smith H, Van Veldhuizen PJ, Kelly K. Impact Study: MK-0646 (Dalotuzumab), Insulin Growth Factor 1 Receptor Antibody Combined with Pemetrexed and Cisplatin in Stage IV Metastatic Non-squamous Lung Cancer. Front Oncol. 2016 Jan 13;5:301. doi: 10.3389/fonc.2015.00301. eCollection 2015.

  PMID: 26793618 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Pleural Effusion; Insulin-Like Growth Factor I, Resistance To

Interventions

dalotuzumab; Cisplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Pleural Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Chao H Huang, MD, FACP

  University of Kansas Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2008
• First Posted: November 27, 2008
• Study Start: June 1, 2009
• Primary Completion: February 1, 2011
• Study Completion: July 1, 2014
• Last Updated: November 7, 2014

Record last verified: 2013-12

Locations

US (4)