Clinical Study Of PI3K/mTOR Inhibitors In Combination With An Oral MEK Inhibitor Or Irinotecan In Patients With Advanced Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Pfizer
Information provided by (Responsible Party):
Pfizer Identifier:
First received: May 2, 2011
Last updated: September 8, 2014
Last verified: September 2014

After the second protocol amendment two study arms are evaluated in this clinical protocol: PD-0325901 (oral MEK inhibitor) plus PF-05212384 (intravenous PI3K/mTOR inhibitor) and PF-05212384 plus irinotecan. The study will assess safety, pharmacokinetics and pharmacodynamics of these combinations in patients with advanced cancer. Once the maximum tolerated doses are identified, further assessment of these combinations will be done in patients with previously treated metastatic colorectal cancer or pancreatic cancer for the PF-05212384 plus irinotecan arm and in patients with KRAS mutated colorectal cancer for the combination of PF-05212384 plus PD-0325901.

Condition Intervention Phase
Advanced Cancer
Drug: PF-05212384
Drug: PD-0325901
Drug: irinotecan
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: A Multi-Arm Phase 1 Dose Escalation Study Of The Safety, Pharmacokinetics, And Pharmacodynamics Of The Dual PI3K/mTOR Inhibitors PF-04691502 And PF-05212384 In Combination With Experimental Or Approved Anticancer Agents In Patients With Advanced Cancer

Resource links provided by NLM:

Further study details as provided by Pfizer:

Primary Outcome Measures:
  • First cycle Dose Limiting Toxicities (DLTs) [ Time Frame: up to 28 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Adverse Events as characterized by type, frequency, severity (as graded by NCI CTCAE v.4.0), timing , seriousness and relationship to study therapy [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
  • Area under the plasma concentration versus time curve (AUC) of PF-04691502, PF-05212384 and PD-0325901 [ Time Frame: 0, 1, 2, 8 and 24 hours post dose ] [ Designated as safety issue: No ]
  • Objective Tumor Response Rate (ORR) [ Time Frame: 15 months ] [ Designated as safety issue: No ]
  • Expression and/or phosphorylation in biopsied tumor tissue of PI3K pathway proteins and markers of cell cycle and survival [ Time Frame: at baseline and at 2 weeks ] [ Designated as safety issue: No ]
  • Gene and/or protein expression in biopsied tumor tissue relating to PI3K and/or MAPK pathway signaling [ Time Frame: at baseline ] [ Designated as safety issue: No ]

Estimated Enrollment: 120
Study Start Date: October 2011
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm D: PF-05212384 + PD-0325901 Drug: PF-05212384
PF-05212384 intravenous infusion weekly starting at 110 mg.
Drug: PD-0325901
PD-0325901 Oral twice daily (BID) dosing 2 mg BID 3 weeks on 1 week off
Experimental: Arm C: PF-05212384 + irinotecan Drug: PF-05212384
PF-05212384 intravenous infusion weekly starting at 95 mg.
Drug: irinotecan
Irinotecan by intravenous infusion at 180 mg/m2 every two weeks (Q x 2 week)


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histological or cytological diagnosis of advanced/metastatic solid tumor for which there is no currently clinically effective treatment.
  • All tumor types for patients enrolled in Stage 1 of Arm C.
  • For patients enrolled in Stage 2 of Arm C, advanced colorectal cancer (both KRAS mutated and KRAS wild type), which has progressed on irinotecan-based regimens, and pancreatic ductal adenocarcinoma after progression on first line treatment for metastatic/advanced disease.
  • For patients enrolled in Stage 1 of Arm D, tumors with KRAS or BRAF mutation (archived or fresh biopsy). Patients with tumors harboring other mutations that activate the MAPK pathway may be enrolled upon agreement with the Sponsor.
  • For patients enrolled in Stage 2 of Arm D, advanced colorectal cancer KRAS mutated (archived or fresh biopsy), which has progressed on irinotecan-based regimens.
  • Patients with colorectal cancer enrolled to both Arms must:

    1. have received at least 6 weeks of irinotecan-based therapy (either as single agent or in combination with cytotoxic drugs or in combination with targeted therapies) as the last prior treatment
    2. have progressed on or within 1 month of completing this irinotecan-based regimen
  • All patients must provide an archived or fresh tumor sample.
  • For a subset of patients fresh tumor biopsies are mandatory:

    1. All patients with CRC enrolled to Stage 2 of Arm C must provide a fresh tumor biopsy at baseline. A subset of patients (10 or more) with at least 5 evaluable patients with CRC KRAS wild type must also provide tumor biopsy during treatment.
    2. Paired fresh tumor biopsies at baseline and an on treatment biopsy are also mandatory for 10 patients enrolled to Stage 2 of Arm D.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) must be 0 or 1
  • Adequate Bone Marrow, Renal, Cardiac, and Liver Function

Exclusion Criteria:

  • -Patients with known active brain metastases
  • -Chemotherapy, radiotherapy (other than palliative radiotherapy to lesions that will not be followed for tumor assessment on this study, ie, non target lesions), biological or investigational agents within 4 weeks of the start of the study treatment (6 weeks for mitomycin C or nitrosoureas).
  • -Any surgery (not including minor procedures such as lymph node biopsy, needle biopsy, and/or placement of port-a-cath) within 4 weeks of start of the study treatment; or not fully recovered from any side effects of previous procedures.
  • -In Arm D only: Patients with glaucoma, intraocular pressure > 21 mmHg, history of retinal vein occlusions, ocular ischemia or any other clinically significant abnormality in the ophthalmologic exam which would make the patient inappropriate for entry into this study
  • -For patients enrolling in Stage 2 prior therapy with an agent that is known or proposed to be active by action on PI3K and/or mTOR.
  • -Prior high dose chemotherapy requiring hematopoietic stem cell transplantation within 12 months of study treatment start.
  • -Known impaired pulmonary function or demonstrated to be impaired by Pulmonary Function Test (PFT) for patients who present with clinical suggestion of impairment.
  • -Uncontrolled or significant cardiovascular disease
  • -Current use or anticipated need for food or drugs that are known potent CYP3A4 inhibitors
  • - Current or anticipated need for food or drugs that are known potent CYP3A4 inducers
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01347866

Contact: Pfizer Call Center 1-800-718-1021

United States, California
Pfizer Investigational Site Recruiting
Los Angeles, California, United States, 90095
Pfizer Investigational Site Recruiting
Los Angeles, California, United States, 90095-6984
Pfizer Investigational Site Recruiting
Santa Monica, California, United States, 90404
United States, Colorado
Pfizer Investigational Site Recruiting
Aurora, Colorado, United States, 80045
United States, South Carolina
Pfizer Investigational Site Recruiting
Charleston, South Carolina, United States, 29425
Canada, Ontario
Pfizer Investigational Site Recruiting
Toronto, Ontario, Canada, M5G 2M9
Pfizer Investigational Site Recruiting
Milano, Italy, 20132
Pfizer Investigational Site Recruiting
Barcelona, Spain, 08035
Sponsors and Collaborators
Study Director: Pfizer Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer Identifier: NCT01347866     History of Changes
Other Study ID Numbers: B1271002
Study First Received: May 2, 2011
Last Updated: September 8, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Advanced metastatic cancer (solid tumors)

Additional relevant MeSH terms:
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses
Topoisomerase I Inhibitors
Topoisomerase Inhibitors processed this record on October 22, 2014