SOLICITATION NOTICE
A -- A Prospective Randomized Trial of Carbon Ion versus Conventional Radiation Therapy for Locally Advanced Unresectable Pancreatic Cancer - Broad Agency Announcement
- Notice Date
- 4/17/2015
- Notice Type
- Combined Synopsis/Solicitation
- NAICS
- 541712
— Research and Development in the Physical, Engineering, and Life Sciences (except Biotechnology)
- Contracting Office
- Department of Health and Human Services, National Institutes of Health, National Cancer Institute, Office of Acquisitions, 9609 Medical Center Drive, Room 1E128, Rockville, Maryland, 20852, United States
- ZIP Code
- 20852
- Solicitation Number
- BAA-N01CM51007-51
- Archive Date
- 6/2/2015
- Point of Contact
- Corwin Stephens, Phone: 240-276-5362, MaryAnne Golling, Phone: 240-276-6981
- E-Mail Address
-
corwin.stephens@nih.gov, gollingm@mail.nih.gov
(corwin.stephens@nih.gov, gollingm@mail.nih.gov)
- Small Business Set-Aside
- N/A
- Description
- Broad Agency Announcement for A Prospective Randomized Phase 3 Trial of Carbon Ion versus Conventional Radiation Therapy for Locally, Advanced, Unresectable Pancreatic Cancer I. INTRODUCTION The Radiation Research Program (RRP) is responsible for the National Cancer Institute's (NCI) clinically-related extramural radiation research program. As part of ongoing efforts to stimulate research in radiotherapy and radiation biology, the RRP supports basic, translational, and clinical research in the Division of Cancer Treatment and Diagnosis (DCTD) by: -Providing expertise to investigators and potential grantees who perform cutting-edge research with radiation and other forms of energy -Helping to lead the radiotherapy research community in establishing priorities for the future direction of radiation research, including interagency cooperation and collaboration -Developing and promoting collaborative efforts among extramural investigators for both preclinical and clinical investigations -Creating unique models and capabilities to help and mentor medically underserved communities in the United States and worldwide to access cancer clinical trials -Evaluating the effectiveness of radiation research being conducted by NCI grantees -Advising the NCI-funded clinical trials groups and the Cancer Therapy Evaluation Program (CTEP) regarding scientific priorities and quality assurance in clinical studies with radiotherapy -Through the Molecular Radiation Therapeutics Branch, providing guidance to extramural investigators, collaborating with DCTD experts and working with colleagues in the Frederick National Laboratory for Cancer Research to develop novel combined modality therapy. -Serving as the NCI's liaison and advisor on the mitigation of radiation injury to normal tissue and the development of biomarkers for radiation injury in programs addressing radiological and nuclear terrorism in the National Institute of Allergy and Infectious Diseases (NIAID) and the Office of the Assistant Secretary for Preparedness and Response within the Department of Health and Human Services. II. BACKGROUND Radiotherapy is an important part of the treatment of unresectable pancreatic cancer. Although older trials were inconsistent, a recent ECOG Phase 3 trial showed a survival advantage to the combination of radiotherapy and gemcitabine over gemcitabine alone (Loehrer 2011). The study was closed early because of slow accrual; however, in the 74 patients enrolled, median survival improved from 9.2 to 11.1 months (p=0.017). These results, together with the recent recognition that uncontrolled local growth is the cause of death in 30% of patients (Iacobuzio-Donahue et al., 2009) lend support to the notion that survival may be improved in some patients with unresectable pancreatic cancer through intensification of local therapy. Previous attempts to escalate the radiation dose to pancreatic tumors, with or without chemotherapy, have been limited by severe toxicity. Intensity Modulated Radiation Therapy (IMRT) can reduce the radiation dose to Organs-At-Risk and simultaneously allow an increase in target dose in this patient population (Spalding 2007). IMRT was used in a phase I/II trial (Ben-Josef 2012) at the University of Michigan to escalate the dose from 50 to 60 Gy in 25 fractions delivered concurrently with full-dose gemcitabine (1000 mg/m2 weekly on weeks 1, 2, 4, and 5 of radiotherapy). Dose-limiting toxicity was defined as Grade 3 gastrointestinal toxicity, neutropenic fever/infection, or substantial deterioration (to Zubrod ≥3) of performance status, occurring between day 1 and 126. The trial accrued 50 patients and established that high-dose radiotherapy (55 Gy in 25 fractions) can be delivered safely with concurrent full-dose gemcitabine, with the use of IMRT. The rate of severe toxicity (24%) observed at this dose compares favorably with toxicities reported with other contemporaneous regimens. There were also encouraging signals of efficacy. The median and 2-year survival in this trial (14.8 months and 30%, respectively) are significantly better than historical controls (11.2 months and 13%, respectively) (Murphy et al 2007). These results also compare favorably to other contemporary phase II and III trials in this patient population, with either 5-FU based- or gemcitabine-based platform. High-dose radiotherapy also improved the 2-year local control from 38% (historical controls, Murphy et al 2007) to 59%. Most importantly, 12 of 50 patients (24%) receiving high-dose radiotherapy were able to undergo resection with good outcomes; 10 patients (83%) had R0 resection and 5 patients (42%) had a major pathological response. The median survival in these patients was 32 months. Particle radiation therapy offers advantageous physical dose distribution (protons and heavy-ion particles) and biological characteristics (heavy-ion particles) as compared to photon radiotherapy. Such charged-particle beams have the physical advantage in that they stop at a depth defined by their energy and thereby spare normal tissues from unwanted radiation. And, while there is still a pressing need for more extensive clinical trials to determine appropriate and optimal use of particle therapy, a considerable body of experimental and treatment-based evidence indicates that particle beams might be as or more effective in treating cancer as the most sophisticated photon-based therapies while definitely reducing the normal tissue irradiated. Because of the physical stopping of protons and other heavy-ion particles at well-defined depth in the tissue, particle beam treatments may target tumors from a single or just a few directions which can be chosen to avoid the most sensitive tissues/organs. Due to the limited volume of tissue irradiated and concomitant reduced risk for the development of radiation-associated site effects, patients with lung cancer and cancers of the head and neck, brain, base of skull, eye, pancreas, and prostate stand to benefit from the advantages of particle beam therapy. In addition to advantageous physical characteristics, heavier-ion particle (most commonly carbon ions) beams produce unique biological effects in tissues. First, radiobiological experiments show that hypoxic tumor cells - the most radiation resistant and aggressive tumor cells - are killed more efficiently with heavy-ion beams than with photons or protons. Second, such particle beams provide a unique advantage of higher biological effectiveness, resulting in more damage to the irradiated tissue per unit of radiation dose delivered to the target volume (at the Bragg pick) as compared to that inflicted in traversed normal tissues. Therefore, radiation resistant tumors, hypoxic tumors could be efficiently eradicated by carbon ion beams without significant collateral damage to normal tissues. Recently, NIRS (Japan) reported that after carbon ion radiotherapy plus chemotherapy of locally advanced pancreatic cancer the 2-year survival rate was 54% (personal communication). Those data were reviewed during visits to NIRS by investigators from the Mayo Clinic and the GI committee of NRG and found to be credible. These data indicate that CIRT can be delivered safely and results in encouraging local control rates and OS. Furthermore, it strongly suggests that survival can be extended in some patients with unresectable pancreatic cancer through improvement in local control and prevention or delay of local complications, which lead to death. III. TECHNICAL OBJECTIVES The overall objective of this BAA is to conduct a definitive randomized phase 3 clinical trial of carbon ion radiotherapy (CIRT) vs. 3D conformal radiation therapy (3D-CRT) for unresectable pancreatic cancer. The clinically relevant outcomes of this trial shall also be indirectly compared to those of parallel trial, RTOG1201, carried out by NRG Oncology (http://www.nrgoncology.org/), a member organization of the NCI Clinical Trials Network (NCTN, http://www.cancer.gov/clinicaltrials/nctn). The Contractor shall provide essential clinical trials infrastructure and laboratory support to carry out and assess the outcome of randomized clinical trial according to the specific research protocol, to be developed by the Contractor. The Contractor shall have the capacity to perform studies using both CIRT and 3D-CRT. The goals of the program are: 1. To conduct a randomized clinical trial necessary to assess the value of CIRT for unresectable pancreatic cancer as directly compared to 3D-CRT. 2. To enable indirect comparison of this trial outcome to the outcome of the IMRT vs. 3D-CRT trial carried out by NRG Oncology (RTOG1201). To meet the objectives of this acquisition, the contractor shall: 1. Set up the infrastructure, with the appropriate number and mix of clinical, laboratory, and support personnel, to conduct a definitive randomized clinical trial comparing 3D-CRT and CIRT as described in the Protocol. 2. Establish collaboration and maintain very close communication throughout with NRG Oncology in order to ensure comparability of the control (3D-RT arm of the CIRT trial with RTOG1201) and to enable indirect comparisons between the two investigational radiation treatment modalities being studied: IMRT and CIRT. 3. Recruit patients for the clinical trial to assess the potential of CIRT, according to the protocol. 4. Follow each subject until death or for a minimum of 2 years. 5. Conduct studies in compliance with Good Clinical Practice (GCP) guidelines and other regulatory requirements governing the safe conduct of research involving human subjects. 6. Obtain and process biospecimens as described in the protocol. Guidelines to be followed can be found at: http://biospecimens.cancer.gov/bestpractices/2011-NCIBestPractices.pdf NOTE: Organizations responding to this BAA must have documented expertise in clinical research and clinical research in the patient population proposed or in the type of study proposed, and demonstrated knowledge of applicable regulatory guidelines.
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