You are here

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

Last updated on March 22, 2018

FOR MORE INFORMATION
Study Location
Ronald Reagan UCLA Medical Center
Los Angeles, California, 90095-6984 United States
Contact
1-800-718-1021
Eligibility criteria
Condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Advanced Cancer
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18+ years
Inclusion criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- 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, ovarian cancer which has progressed on
prior platinum containing regimen or KRAS mutated non small cell lung cancer which has
progressed on one prior regimen.

- 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:

a. 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.

- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) must be 0 or 1

- Adequate Bone Marrow, Renal, Cardiac, and Liver Function

Exclusion criteria
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details

- -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

NCT01347866
Pfizer
Terminated
Clinical Study Of PI3K/mTOR Inhibitors In Combination With An Oral MEK Inhibitor Or Irinotecan In Patients With Advanced Cancer

NEED INFO?

Questions about a trial? Call or email to reach a Pfizer Clinical Trial Contact Center

Pfizer Clinical Trials Contact Center

1-800-718-1021

[email protected]

call now

Try a new search

Search for Clinical Trials by condition, keyword or trial number. Share your location or enter your zip code, city, or country to find studies near you.
Clinical Study Of PI3K/mTOR Inhibitors In Combination With An Oral MEK Inhibitor Or Irinotecan In Patients With Advanced Cancer
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
After the fourth 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 or pancreatic cancer for the PF-05212384 plus irinotecan arm and in patients with ovarian cancer or KRAS mutated non small cell lung cancer for the combination of PF-05212384 plus PD-0325901.
The study was prematurely discontinued as a result of an internal portfolio review on April 1, 2015. The decision to terminate was not due to any safety or efficacy data.
Interventional
Phase 1
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Advanced Cancer
  • 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
  • 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)
  • Experimental: Arm D: PF-05212384 + PD-0325901
    Interventions:
    • Drug: PF-05212384
    • Drug: PD-0325901
  • Experimental: Arm C: PF-05212384 + irinotecan
    Interventions:
    • Drug: PF-05212384
    • Drug: irinotecan
Not Provided


*   Includes publications given by the data provider as well as publications
identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
105
December 2015
December 2015   (Final data collection date for primary outcome measure)

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, ovarian cancer which has progressed on prior platinum containing regimen or KRAS mutated non small cell lung cancer which has progressed on one prior regimen.
  • 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:

    a. 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.

  • 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
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Canada,   Italy,   Spain,   United States
 
 
NCT01347866
B1271002
2011-001671-39 ( EudraCT Number )
No
Not Provided
Not Provided
Pfizer
Pfizer
Not Provided
Study Director: Pfizer CT.gov Call Center Pfizer
Pfizer
January 2016

ICMJE     Data element required by the

International Committee of Medical Journal Editors
and the
World Health Organization ICTRP

FOR MORE INFORMATION

Contact a representative by phone, email, or visiting thte study website. To get updates and notications about this trail, sign up using the form below.

BY PHONE

Pfizer Clinical Trials Contact Center

1-800-718-1021

BY EMAIL

Contact

[email protected]



Call Now