Oncology Research Program

Highlights of the NCCN Oncology Research ProgramThe NCCN Oncology Research Program (ORP) strives to improve the quality of life for patients and reduce cancer-related deaths by advancing cancer therapies through research. Since the program's establishment in 1999, the NCCN ORP has brought millions of dollars in research grants to investigators at NCCN Member Institutions. Research grants are provided to NCCN through collaborations with pharmaceutical and biotechnology companies; these grants are in turn used to support scientifically meritorious cancer research efforts.NCCN ORP studies typically explore new avenues of clinical investigation and seek answers to important cancer-related questions. All studies are approved and funded through a scientific peer-review process and are overseen by the ORP.Several NCCN-sponsored studies funded through the grant mechanism are highlighted below.A Phase I/II Trial of Temsirolimus Plus Neratinib for Patients With Metastatic HER2-Amplified or Triple Negative Breast CancerPrincipal Investigator: Sarat Chandarlapaty, MD, PhDCondition: Breast cancerInstitution: Memorial Sloan-Kettering Cancer CenterThis is an open-label, single arm, dose-escalation phase I/II study to determine the maximum tolerated dose (MTD) of temsirolimus with daily neratinib and to determine the safety and efficacy of this combination for patients with advanced breast carcinoma. Patients with trastuzumab-refractory HER2-amplified disease or triple-negative disease will be enrolled in both phases. In the phase I portion (now completed), both types of patients were enrolled; in the phase II portion, each type of patient will be enrolled and studied in separate cohorts.A treatment cycle consists of 28 days on the following...

Highlights of the NCCN Oncology Research Program

The NCCN Oncology Research Program (ORP) strives to improve the quality of life for patients and reduce cancer-related deaths by advancing cancer therapies through research. Since the program's establishment in 1999, the NCCN ORP has brought millions of dollars in research grants to investigators at NCCN Member Institutions. Research grants are provided to NCCN through collaborations with pharmaceutical and biotechnology companies; these grants are in turn used to support scientifically meritorious cancer research efforts.

NCCN ORP studies typically explore new avenues of clinical investigation and seek answers to important cancer-related questions. All studies are approved and funded through a scientific peer-review process and are overseen by the ORP.

Several NCCN-sponsored studies funded through the grant mechanism are highlighted below.

A Phase I/II Trial of Temsirolimus Plus Neratinib for Patients With Metastatic HER2-Amplified or Triple Negative Breast Cancer

Principal Investigator: Sarat Chandarlapaty, MD, PhD

Condition: Breast cancer

Institution: Memorial Sloan-Kettering Cancer Center

This is an open-label, single arm, dose-escalation phase I/II study to determine the maximum tolerated dose (MTD) of temsirolimus with daily neratinib and to determine the safety and efficacy of this combination for patients with advanced breast carcinoma. Patients with trastuzumab-refractory HER2-amplified disease or triple-negative disease will be enrolled in both phases. In the phase I portion (now completed), both types of patients were enrolled; in the phase II portion, each type of patient will be enrolled and studied in separate cohorts.

A treatment cycle consists of 28 days on the following schedule:

  • Neratinib orally once daily with food, preferably in the morning
  • Weekly temsirolimus given intravenously on days 1, 8, 15, and 22.

Phase I was designed with a standard 3 + 3 dose escalation schedule. The MTD was determined to be 8 mg intravenously weekly in combination with daily neratinib.

Phase II includes 2 cohorts: patients with HER2-amplified and those with triple-negative breast cancer. Each cohort has a Simon 2-stage design to determine the efficacy of temsirolimus administered in combination with neratinib. Both pathologic subtypes of patients will be studied separately, though accrual will be simultaneous. Response (RECIST criteria) will be assessed every 8 weeks (every 2 cycles) after the start of therapy.

Primary Outcome Measures:

  • Determine the MTD of weekly intravenous temsirolimus administered in combination with a fixed dose of daily oral neratinib therapy (phase I)
  • Estimate the efficacy (overall response rate = complete response and partial response) by RECIST criteria of combination temsirolimus and neratinib at the established MTD for both patients with HER2-amplified trastuzumab-refractory and those with triple-negative disease (phase II)

Secondary Outcome Measures:

  • Determine the safety and tolerability of combination temsirolimus and neratinib
  • Estimate secondary efficacy end points of this combination, including progression-free survival and duration of response
  • Determine expression level of HER2 and p95-HER2 in metastatic tissue samples and correlate this with response to combination temsirolimus and neratinib in HER2-amplified tumors
  • Assess abnormalities in PI3K-PTEN-AKT-mTOR pathway through analysis of expression of PTEN and upstream molecular targets IGF1-R, EGFR, and HER3, and mutational activation of PI3K in the metastatic tumor samples
  • Determine if the addition of neratinib affects the exposure and half-life of temsirolimus and its active metabolite, sirolimus

Contact: Sarat Chandarlapaty, MD, PhD • 212-639-5449

ClinicalTrials.gov Identifier: NCT01111825

Phase I Trial of Intraperitoneal Nab-Paclitaxel (Abraxane) in the Treatment of Advanced Malignancies Primarily Confined to the Peritoneal Cavity

Principal Investigator: Mihaela Cristea, MD

Condition: Ovarian cancer, peritoneal cavity cancer

Institution: City of Hope Comprehensive Cancer Center

Patients receive intraperitoneal paclitaxel albumin-stabilized nanoparticle formulation on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Plasma and peritoneal fluid samples are collected on cycle 1, day 1 for pharmacokinetic analysis by liquid chromatography and mass spectrometry. Patients are followed up for 4 weeks after completion.

Primary Objectives:

  • Determine the MTD of nab-paclitaxel (Abraxane) as a single agent administered intraperitoneally via an intraperitoneal catheter

Secondary Objectives:

  • Evaluate the pharmacokinetics of nab-paclitaxel in the plasma and peritoneum when administered directly into the peritoneal cavity
  • Determine the potential pharmacokinetic advantage (favorable ratio of nab-paclitaxel concentration in the peritoneal cavity vs. plasma) for nab-paclitaxel administered intraperitoneally
  • Determine the progression of peripheral neuropathy in patients treated with intraperitoneal chemotherapy through pretreatment and sequential evaluation of the Neuropathic Pain Syndrome Inventory and Serial Nerve Conduction Studies

Contact: Clinical Trials Office - City of Hope Medical Center • 800-826-4673 • becomingapatient@coh.org

ClinicalTrials.gov Identifier: NCT00825201

The goal of the Highlights of the NCCN Oncology Research Program (ORP) is to provide readers with more information on the ORP, including studies currently accruing patients.

For more information on specific trials, including patient selection criteria, please use the contact information listed with each study.

For more information on the NCCN ORP, including a complete detailing of the clinical studies currently underway at NCCN Member Institutions, please access the NCCN ORP pages at http://www.nccn.org/clinical_trials/clinicians.asp.

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