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

NCT01347866 | Terminated Phase 1 Results

• 2 other identifiers: B12710022011-001671-39
• Study Type: interventional
• Target: 105
• Locations: 4 countries
• Sites: 18

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.

Conditions

Advanced Cancer

Keywords

Advanced metastatic cancer (solid tumors); PI3K; mTOR; MEK

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Dose-Limiting Toxicities (DLTs) in First Cycle (28 Days)

  DLT was defined as any of the following hematologic or non-hematologic events which were attributable to the combination study drug and occurring in the first 28-day cycle: 1) Grade 4 neutropenia lasting greater than (\>)7 days; 2) Febrile neutropenia (defined as neutropenia greater than or equal to \[≥\]Grade 3 and a body temperature ≥38.5°C); 3) Grade ≥3 neutropenic infection; 4) Grade 3 thrombocytopenia with bleeding; 5) Grade 4 thrombocytopenia; 6) Grade ≥3 toxicities; 7) Persistent, intolerable toxicities which resulted in failure to deliver at least 75% of doses during the first cycle; 8) Persistent, intolerable toxicities which resulted in delay of start of Cycle 2 by more than 2 weeks of scheduled day; 9) Persistent Grade 3 QTc prolongation (QTc \>500 msec) after correction of any reversible causes.

  Baseline up to 28 days

Secondary Outcomes (44)

• Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Baseline up to End of Treatment (EOT) (within 28 days after last treatment administration)

• Number of Participants With Treatment-Emergent AEs (TEAEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 4.0) Grade

  Baseline up to End of Treatment (EOT) (within 28 days after last treatment administration)

• Number of Participants With Laboratory Test Abnormalities (Hematology)

  Baseline, Days 1, 15, and 23 of Cycle 1, Days 1 and 15 of Cycle 2, Day 1 of Cycle 3 and subsequent cycles, up to End of Treatment (within 28 days of last treatment administration)

• Number of Participants With Laboratory Test Abnormalities (Coagulation)

  Baseline, Days 1 and 15 of Cycle 1, Days 1 and 15 of Cycle 2, Day 1 of Cycle 3 and subsequent cycles, up to End of Treatment (within 28 days of last treatment administration)

• Number of Participants With Laboratory Test Abnormalities (Chemistry)

  Baseline, Days 1, 15, and 23 of Cycle 1, Days 1 and 15 of Cycle 2, Day 1 of Cycle 3 and subsequent cycles, up to End of Treatment (within 28 days of last treatment administration)

Study Arms (2)

Arm D: PF-05212384 + PD-0325901

EXPERIMENTAL

Drug: PF-05212384; Drug: PD-0325901

Arm C: PF-05212384 + irinotecan

EXPERIMENTAL

Drug: PF-05212384; Drug: irinotecan

Interventions

PF-05212384 DRUG

PF-05212384 intravenous infusion weekly starting at 110 mg.

Arm D: PF-05212384 + PD-0325901

PD-0325901 DRUG

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

Arm D: PF-05212384 + PD-0325901

irinotecan DRUG

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

Arm C: PF-05212384 + irinotecan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Pfizer: lead

Study Sites (18)

Ronald Reagan UCLA Medical Center

Los Angeles, California, 90095-6984, United States

Location

Ronald Reagan UCLA Medical Center

Los Angeles, California, 90095, United States

Location

UCLA Medical Center

Los Angeles, California, 90095, United States

Location

UCLA Oncology Center

Los Angeles, California, 90095, United States

Location

Santa Monica - UCLA Medical Center and Orthopaedic Hospital

Santa Monica, California, 90404, United States

Location

UCLA Santa Monica Hematology Oncology

Santa Monica, California, 90404, United States

Location

Anschutz Cancer Pavilion

Aurora, Colorado, 80045, United States

Location

University of Colorado Denver (CTRC)

Aurora, Colorado, 80045, United States

Location

University of Colorado Hospital Anschutz Inpatient Pavilion

Aurora, Colorado, 80045, United States

Location

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Medical University of South Carolina, Hollings Cancer Center

Charleston, South Carolina, 29425, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

MUSC, Investigational Drug Services

Charleston, South Carolina, 29425, United States

Location

MUSC Health East Cooper

Mt. Pleasant, South Carolina, 29464, United States

Location

MUSC Specialty Care-North

North Charleston, South Carolina, 29406, United States

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Ospedale San Raffaele

Milan, 20132, Italy

Location

Hospital General Vall d'Hebron

Barcelona, 08035, Spain

Location

Related Links

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

MeSH Terms

Interventions

gedatolisib; mirdametinib; Irinotecan

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds

Limitations and Caveats

This study was terminated prematurely for strategic reasons based on an internal portfolio prioritization.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2011
• First Posted: May 4, 2011
• Study Start: October 1, 2011
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: October 29, 2018
• Results First Posted: October 29, 2018

Record last verified: 2018-02

Locations

IT (1); CA (1); ES (1); US (15)