Clinical trial NCT01204099: Study of PX-866 and Docetaxel in Solid Tumors
Official title: Phase 1/2 Study of PX-866 and Docetaxel in Patients With Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Non Small Cell Lung Cancer (NSCLC)
Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Keywords: PX-866
Non small cell lung cancer
solid tumors
Squamous cell cancer of the head and neck
docetaxel
NSCLC
taxotere
SCCHN
PI-3K
PI3 kinase
PI3K
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
First posted: 2010-09-17
Enrollment: 223
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Phase 1: To determine the maximally tolerated dose (MTD) or recommended dose (RD) and any potential efficacy of PX-866 in combination with docetaxel in patients with solid tumors.

Phase 2: To determine the antitumor activity and safety of PX-866 in combination with docetaxel versus docetaxel alone in patients with NSCLC or SCCHN.

Detailed description: This is a Phase 1/2 open-label study. In the Phase 1 part of the study, PX-866 was given in combination with docetaxel to patients with incurable locally advanced, recurrent or metastatic cancer.

Phase 2 of the study is an open-label, randomized evaluation of the antitumor activity and safety of PX-866, administered at the MTD/RD identified in Phase 1 (8mg daily), in combination with docetaxel versus docetaxel alone in patients with locally advanced, recurrent, or metastatic NSCLC (Group 1) or patients with locally advanced, recurrent, or metastatic SCCHN (Group 2).

Group 1 (patients with locally advanced, recurrent, or metastatic NSCLC) is now closed to enrollment.

All treatments will be administered on a 21-day cycle. Docetaxel 75 mg/m2 will be administered IV on Day 1 of each 21-day cycle. PX-866 will be administered orally or via PEG tube (if applicable) once per day on Days 1 to 21 of all treatment cycles in patients randomized to the treatment arm containing PX-866.

Patients will be evaluated for progression approximately every 6 weeks. Patients with stable disease (SD) or better, per investigator assessment, will receive repeat cycles of treatment on a 21-day schedule until disease progression, unacceptable toxicity or withdrawal of consent.

Eligibility criteria: Inclusion Criteria:

* At least 18 years at time of consent
* Agrees to use a medically accepted form of contraception from the time of consent to completion of all follow up study visits
* If female of child bearing potential, negative pregnancy test (not required for post menopausal females)
* Signed an informed consent document that has been approved by an institutional review board or independent ethics committee (IRB/IEC)
* Has either locally advanced, recurrent, or metastatic NSCLC for which they have received at least 1 and no more than 2 prior systemic treatment regimens that may include up to 1 platinum based chemotherapy regimen and/or an epidermal growth factor receptor (EGFR) inhibitor OR locally advanced, recurrent or metastatic SCCHN for which they have received at least one and no more than two prior systemic treatment regimens.
* Measurable disease per Response Evaluation Criteria In Solid Tumors
* Eastern Cooperative Oncology Group (ECOG) 0 or 1
* In the opinion of the clinical investigator, life expectancy \>3 months
* Adequate hematologic function as defined by:

  * Hemoglobin ≥ 9 g/dL
  * Absolute neutrophil count (ANC) ≥1500 cells/µL
  * Platelets ≥100,000/µL
* Adequate hepatic function as defined by the following:

  * Bilirubin ≤ ULN
  * Aspartate aminotransaminase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤1.5 x upper limit of normal (ULN)
* Creatinine level ≤1.5 x ULN

Exclusion Criteria:

* Has medical, social, or psychosocial factors that, in the opinion of the investigator, could impact safety or compliance with study procedures
* Is breastfeeding
* Treatment with any systemic chemotherapy, epidermal growth factor receptor (EGFR) inhibitor, radiation or experimental agent within 4 weeks of study drug dosing. Washout period following palliative radiation should be discussed with the study medical monitor
* Previous treatment with docetaxel except for patients in Phase 2 who received a docetaxel containing regimen as part of adjuvant or neoadjuvant therapy which was completed at least 6 months prior to study drug dosing
* Previous treatment with a phosphatidylinositol 3 kinase (PI 3K) inhibitor
* Known human immunodeficiency virus (HIV)
* Known or suspected clinically active brain metastases. Previously treated and stable brain metastases are allowable. Stable brain metastases are defined as no change on CT scan or MRI for minimum of two months AND no change in steroid dose for a minimum of four weeks, unless change due to intercurrent infection or other acute event
* Grade \>2 peripheral neuropathy, as defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.02
* Any other significant medical or psychiatric condition that in the opinion of the investigator renders the patient inadequate for participation
* History of severe hypersensitivity reactions to docetaxel or to other drugs formulated with polysorbate

Primary outcomes:
measure: Progression Free Survival
timeFrame: 42 days
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: 42 days
measure: Incidence and severity of adverse events
timeFrame: 42 days
measure: Overall survival
timeFrame: 42 days
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Escondido
country: United States
facility: Southwest Cancer Care
state: California
city: Pleasant Hill
country: United States
facility: Bay Area Cancer Research Group, LLC
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Denver
country: United States
facility: Eastern Colorado Health Care System - Denver VA
state: Colorado
city: Holiday
country: United States
facility: Cancer Center of Pasco-Pinellas
state: Florida
city: Wichita
country: United States
facility: Cancer Center of Kansas
state: Kansas
city: Baltimore
country: United States
facility: John Hopkins University
state: Maryland
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Albuquerque
country: United States
facility: New Mexico Cancer Care Alliance
state: New Mexico
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Latham
country: United States
facility: New York Oncology, Hematology
state: New York
city: New York
country: United States
facility: Beth Israel Hospital
state: New York
city: New York
country: United States
facility: New York University Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Tualatin
country: United States
facility: Northwest Cancer Specialists
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Austin
country: United States
facility: Texas Oncology - South Austin
state: Texas
city: Dallas
country: United States
facility: Mary Crowley Cancer Center
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Baylor Charles A. Sammons Cancer Center
state: Texas
city: Christiansburg
country: United States
facility: Oncology and Hematology Associates of SW Virginia, DBA Blue Ridge Cancer Care
state: Virginia
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Newport News
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Kennewick
country: United States
facility: Columbia Basin Hematology & Oncology
state: Washington
city: Spokane
country: United States
facility: Medical Oncology Associates
state: Washington
city: Yakima
country: United States
facility: Yakima Valley Memorial Hospital/North Star Lodge
state: Washington
city: Winnipeg
country: Canada
facility: Cancer Care Manitoba
state: Manitoba
city: London
country: Canada
facility: London Regional Cancer Program
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Sherbrooke
country: Canada
facility: CHUS Hopital Fleurimont
state: Quebec
Study officials:
References: