Clinical Trial: -02341066 and PF-00299804 for Advanced Non-Small Cell Lung Cancer

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: A Phase 1, Open-Label, Dose Escalation Study to Evaluate Safety, Pharmacokinetics and Pharmacodynamics of Combined Oral C-Met/ALK Inhibitor (PF-02341066) and Pan-Her Inhibitor (PF-0299804) in Patients

Brief Summary:

Background:

- PF-02341066 and PF-00299804 are drugs that specifically target certain proteins that may be more active in cancer cells than normal cells, in particular in non-small cell lung cancer. Both drugs seem to be able to stop the growth of or kill cancer cells. Researchers want to combine them to see if they are a safe and effective treatment for advanced non-small cell lung cancer.

Objectives:

- To test the safety and effectiveness of PF-02341066 and PF-00299804 for advanced non-small cell lung cancer.

Eligibility:

- Individuals at least 18 years of age with advanced non-small cell lung cancer that has not responded to standard treatments.

Design:

  • Participants will be screened with a medical history and physical exam. They will also have blood and urine tests, and imaging studies. Heart and lung function tests and an eye exam may also be given.
  • The first cycle of treatment will be 28 days. Every cycle after the first will be 21 days. Participants may have up to 17 cycles of treatment.
  • Participants will take both study drugs as tablets. Twelve hours after the first dose, participants will take only the PF-02341066. This dose schedule will remain the same throughout the study.
  • Participants will be monitored with frequent blood and urine tests and imaging studies. Tumor biopsies will be taken as needed. Those in the study will keep a diary to record any symptoms or side effects of taking the study drugs.

  • Detailed Summary:

    BACKGROUND:

    • Approximately 85% of lung cancer is defined histologically as NSCLC and the majority of patients present with inoperable locally advanced (Stage IIIB) or metastatic (Stage IV) disease for which no curative treatment is available.
    • Patients with disease progression on or after first-line treatment with platinum-based doublets may be candidates for second-line treatment.
    • Recent evidence strongly implicates EGFR activating somatic mutations as a mechanism of tumorigenesis and a determinant of sensitivity to EGFR TKIs in NSCLC.
    • Despite the dramatic initial response to gefitinib and erlotinib, about 50% of NSCLC tumors develop resistance due to secondary activating mutations in EGFR itself, including the EGFR T790M gatekeeper mutation, and more than 20% of acquired resistance is due to an increase in mesenchymal-epithelial transition factor (c-Met) signaling.
    • There is evidence from a limited number of tumors from patients with acquired resistance to EGFR-TKIs that both T790M and cMET resistance mechanisms can occur in the same patient at different metastatic sites and even in different fractions of the same lesion.
    • Tumors with acquired resistance to erlotinib and gefitinib might be vulnerable to a combination of PF-00299804 a second generation EGFR TKI which is also an inhibitor of T790M mutation, and PF-02341066 which is an inhibitor of c- Met/Hepatocyte Growth Factor Receptor (HGFR).

    OBJECTIVES:

    - To define the recommended Phase 2 dose (RP2D) of combined PF-02341066 plus

    PF-00299804 in patients with advance
    Sponsor: National Cancer Institute (NCI)

    Current Primary Outcome: Overall safety profile of combined PF 02341066 plus PF 00299804 including adverse events (AE), as defined and graded by the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], and first cycle Dose Limiting Tox... [ Time Frame: 18 months ]

    Original Primary Outcome: Overall safety profile of combined PF-0234 1066 plus PF-00299804 including adverse events.

    Current Secondary Outcome:

    • Plasma concentrations and pharmacokinetic (PK) parameters of PF 02341066 and PF 00299804 including AUCtau, Cmax, Ctrough, Tmax, and CLss/F [ Time Frame: 18 months ]
    • Clinical activity of combined PF 02341066 plus PF 00299804 including objective response (OR) and stable disease (SD) as defined by RECIST version 1.1, duration of response (DR) and progression free survival (PFS). [ Time Frame: 18 months ]
    • Biomarkers in tumor and blood that are potentially predictive for drug activity: for example, KRAS mutations, EGFR mutations (eg, T790M), EGFR and HER2 amplifications, c Met amplification and mutations, ALK, PTEN and PIK3A status in tumor biopsi... [ Time Frame: 12 months ]
    • Pharmacodynamic biomarkers in tumor biopsies (e.g., phospho c Met, c Met, EGFR, phospho EGFR) and in blood (e.g., HGF and s Met) that are modulated following drug exposure. [ Time Frame: 12 months ]


    Original Secondary Outcome: PK parameters of PF-02341066 and PF-00299804. Clinical activity of said combined drugs including objective response. Tumor and blood biomarkers that are potentially predictive of drug activity or modulated following drug exposure.

    Information By: National Institutes of Health Clinical Center (CC)

    Dates:
    Date Received: September 24, 2011
    Date Started: September 1, 2011
    Date Completion:
    Last Updated: May 12, 2017
    Last Verified: February 26, 2015