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

NCT ID: NCT01347866

Last Updated: 2018-10-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 105 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-10-31
• Study Completion Date: 2015-12-31

Brief Summary

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.

Detailed Description

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.

Conditions

Advanced Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Arm D: PF-05212384 + PD-0325901

Group Type: EXPERIMENTAL

PF-05212384

Intervention Type: DRUG

PF-05212384 intravenous infusion weekly starting at 110 mg.

PD-0325901

Intervention Type: DRUG

PD-0325901 Oral twice daily (BID) dosing 2 mg BID 3 weeks on 1 week off

Arm C: PF-05212384 + irinotecan

Group Type: EXPERIMENTAL

PF-05212384

Intervention Type: DRUG

PF-05212384 intravenous infusion weekly starting at 95 mg.

irinotecan

Intervention Type: DRUG

Irinotecan by intravenous infusion at 180 mg/m2 every two weeks (Q x 2 week)

Interventions

PF-05212384

PF-05212384 intravenous infusion weekly starting at 110 mg.

Intervention Type: DRUG

PD-0325901

PD-0325901 Oral twice daily (BID) dosing 2 mg BID 3 weeks on 1 week off

Intervention Type: DRUG

PF-05212384

PF-05212384 intravenous infusion weekly starting at 95 mg.

Intervention Type: DRUG

irinotecan

Irinotecan by intravenous infusion at 180 mg/m2 every two weeks (Q x 2 week)

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pfizer CT.gov Call Center

Role: STUDY_DIRECTOR

Pfizer

Locations

Ronald Reagan UCLA Medical Center

Los Angeles, California, United States

Ronald Reagan UCLA Medical Center

Los Angeles, California, United States

UCLA Medical Center

Los Angeles, California, United States

UCLA Oncology Center

Los Angeles, California, United States

Santa Monica - UCLA Medical Center and Orthopaedic Hospital

Santa Monica, California, United States

UCLA Santa Monica Hematology Oncology

Santa Monica, California, United States

Anschutz Cancer Pavilion

Aurora, Colorado, United States

University of Colorado Denver (CTRC)

Aurora, Colorado, United States

University of Colorado Hospital Anschutz Inpatient Pavilion

Aurora, Colorado, United States

University of Colorado Hospital

Aurora, Colorado, United States

Medical University of South Carolina, Hollings Cancer Center

Charleston, South Carolina, United States

Medical University of South Carolina

Charleston, South Carolina, United States

MUSC, Investigational Drug Services

Charleston, South Carolina, United States

MUSC Health East Cooper

Mt. Pleasant, South Carolina, United States

MUSC Specialty Care-North

North Charleston, South Carolina, United States

Princess Margaret Hospital

Toronto, Ontario, Canada

Ospedale San Raffaele

Milan, , Italy

Hospital General Vall d'Hebron

Barcelona, , Spain

Countries

United States; Canada; Italy; Spain

Related Links

https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B1271002&StudyName=Clinical%20Study%20Of%20PI3K/mTOR%20Inhibitors%20In%20Combination%20With%20An%20Oral%20%20MEK%20Inhibitor%20Or%20Irinotecan%20In%20Patients%20With%20Advanced%20Cancer

To obtain contact information for a study center near you, click here.

Other Identifiers

2011-001671-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

B1271002

Identifier Type: -

Identifier Source: org_study_id