Symptoms and General Pathology

All Conditions

Neoplasms

Rare Diseases

Recurrence

Glioblastoma

Glioma

Astrocytoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Anaplastic Astrocytoma

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Temozolomide

Antineoplastic Agents, Alkylating

Alkylating Agents

All patients will receive temozolomide (150 to 200 mg per square meter for 5 days during each 28 day cycle) for a total of 1 year or until the time of disease progression.

All patients will receive 0.5 Gy of radiation therapy twice daily. This study will include a safety run-in component. If \> 33% of patients in the initial cohort of 6 experience grade 3 or greater hematologic toxicity according to the NCI Common Toxicity Criteria version 4, then a dose reduction will occur following the schedule listed below. Otherwise, following a 1 month waiting period after the first cycle of adjuvant LDFRT plus temozolomide for the first cohort of patients, the phase 2 study will open for full accrual. Patients will receive radiation with the first six 28-day cycles of temozolomide.

All patients will receive 0.5 Gy of radiation therapy twice daily. This study will include a safety run-in component. If \> 33% of patients in the initial cohort of 6 experience grade 3 or greater hematologic toxicity according to the NCI Common Toxicity Criteria version 4, then a dose reduction will occur following the schedule listed below.

Low Dose Fractionated Radiation Therapy (LDFRT)

All patients will receive temozolomide (150 to 200 mg per square meter for 5 days during each 28 day cycle) for a total of 1 year or until the time of disease progression.

Kristin Redmond, M.D.

To evaluate the safety and effectiveness of low dose rate radiation therapy plus temozolomide. This will be in patients with High Grade Glioma (to only include Anaplastic Astrocytoma or Glioblastoma Multiforme) who have previously been treated with surgery followed by radiation surgical resection followed by adjuvant radiation therapy plus temozolomide.

In vitro and in vivo studies have suggested that low dose fractionated radiation therapy (LDFRT) may be used to potentiate full dose chemotherapy, decreasing the development of resistance found with standard doses of radiation and chemotherapy. This is a nonrandomized, open label, single institution phase II trial with a safety run-in to evaluate the safety and efficacy of LDFRT plus temozolomide in patients with High Grade Glioma (to only include Anaplastic Astrocytoma or Glioblastoma Multiforme) previously treated with surgical resection followed by adjuvant radiation therapy plus temozolomide. The primary objective of the phase II study is to estimate response rate in patients treated with twice daily fractions of low dose radiation plus temozolomide chemotherapy.

Low Dose Radiation Therapy for Glioblastoma Multiforme

A Phase II Trial of Low Dose Fractionated Radiation Therapy as a Chemo-Potentiator of Salvage Temozolomide for Recurrent Anaplastic Astrocytoma and Glioblastoma Multiforme

To estimate the response rate to salvage temozolomide plus LDFRT.

Overall survival rate is calculated as the median number of months that patients were alive for the cohort

Progression free survival rate is calculated as the median number of months for the cohort until patient's disease worsened/progressed

The number of patients with grade 3+ hematologic toxicities.

The number of patients with reported grade 3+ neurologic toxicities

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Other (Not Including Serious) Adverse Events data was not collected.

All patients will receive temozolomide (150 to 200 mg per square meter for 5 days during each 28 day cycle) for a total of 1 year or until the time of disease progression.

All patients will receive 0.5 Gy of radiation therapy twice daily. This study will include a safety run-in component. If \> 33% of patients in the initial cohort of 6 experience grade 3 or greater hematologic toxicity according to the NCI Common Toxicity Criteria version 4, then a dose reduction will occur following the schedule listed below. Otherwise, following a 1 month waiting period after the first cycle of adjuvant LDFRT plus temozolomide for the first cohort of patients, the phase 2 study will open for full accrual. Patients will receive radiation with the first six 28-day cycles of temozolomide.

Low Dose Fractionated Radiation Therapy (LDFRT): All patients will receive 0.5 Gy of radiation therapy twice daily. This study will include a safety run-in component. If \> 33% of patients in the initial cohort of 6 experience grade 3 or greater hematologic toxicity according to the NCI Common Toxicity Criteria version 4, then a dose reduction will occur following the schedule listed below.

Temozolomide: All patients will receive temozolomide (150 to 200 mg per square meter for 5 days during each 28 day cycle) for a total of 1 year or until the time of disease progression.

Temozolomide With Low Dose Fractionated Radiation Therapy

Age, Continuous

Sex: Female, Male

white

black

other

Race/Ethnicity, Customized

United States

Region of Enrollment

met baseline criteria per protocol

Kristin Redmond, MD

Response Rate

Overall Survival Rate

Progression Free Survival Rate

Number of Patients With Hematologic Toxicities

Number of Patients With Neurologic Toxicity

Overall Study

Digestive System Diseases

Adenocarcinoma

Rectal Neoplasms

Carcinoma

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Rectal Diseases

Micronutrients

Hematinics

Vitamins

Leucovorin

Fluorouracil

Oxaliplatin

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Antidotes

Protective Agents

Folic Acid

Vitamin B Complex

Trace Elements

Folate

Vitamin B9

Part I:

FOLFOX: combination of drugs administered in a specific sequence as prescribed below.

* Oxaliplatin: 85 mg/m2 intravenously (IV) over 2 hours
* Leucovorin: 200 mg/m2 IV bolus over 2 hours
* 5-FU: 400 mg/m2 IV bolus over 5-15 minutes, then 2,400 mg/m2 continuous IV infusion over 46-48 hours

Part II:

Low dose fractionated radiation therapy (LDFRT) Intensity-modulated, bone marrow sparing, whole pelvic radiation therapy 40 cGy fractions twice per day delivered at least 4-6 hours apart on the first 2 days of each chemotherapy cycle for a total of 6 cycles

FOLFOX {5-fluorouracil (5-FU), leucovorin, and oxaliplatin}

Low dose fractionated radiation therapy (LDFRT)

Shahed Badiyan, MD

The purpose of this study is to assess the effects, both good and bad, of adding very low dose fractionated radiation therapy (LDFRT) to the pelvis, with FOLFOX chemotherapy prior to surgery. Standard pelvic radiation therapy given once a day (Monday through Friday) over approximately 5.5 weeks is not given in this study. You will receive 6 cycles of FOLFOX (each cycle is 2 weeks) and you will also get an LDFRT to your pelvis given twice a day on the first two days of each cycle.

The current standard of care for treatment of locally advanced rectal cancer consists of neoadjuvant whole pelvic RT with radiosensitizing single-agent 5-FU followed by surgery and adjuvant full dose chemotherapy (typically FOLFOX). For all clinical T3, T4, and/or lymph node positive rectal cancer patients the standard neoadjuvant radiation dose per fraction is 180 cGy delivered on consecutive weekdays over 5.5 weeks for a total of 5040 cGy. A potentially paradigm-changing approach is currently being investigated in a phase II/III trial in which neoadjuvant RT is omitting in favor of using full dose FOLFOX chemotherapy based on provocative data published from Memorial Sloan Kettering Cancer Center. We hypothesize that whole pelvic LDFRT using 40 cGy fractions for a total of 960 cGy can be safely added concurrently to neoadjuvant full dose FOLFOX as an alternative to standard neoadjuvant 5-FU chemoradiation. We further hypothesize that using LDFRT as a chemopotentiatior will significantly increase the pCR rate as reported by the Memorial Sloan Kettering pilot study of 27%. Lastly, due to the significantly lower radiation dose per fraction and lower total radiation dose we expect that this novel strategy will not cause higher rates of severe toxicity compared to neoadjuvant FOLFOX alone.

Specifically, this phase II trial intends to determine whether 6 cycles of neoadjuvant FOLFOX with concurrent LDFRT followed by comprehensive restaging and TME achieves favorable outcomes for patients with T3N0M0, T3N1M0, or T2N1M0 rectal cancer. As mentioned above, the current standard of care for all locally advanced rectal cancer patients includes radiosensitizing 5-FU and concurrent whole pelvic RT to 5040 Gy in 180 Gy once daily fractions. Per the proposed protocol, T3N0M0, T3N1M0, or T2N1M0 rectal cancer patients who are eligible to undergo a low anterior resection would receive whole pelvic RT to 960 cGy in 40 cGy fractions delivered twice daily on days 1-2 of each cycle of FOLFOX chemotherapy for a total of 6 cycles.

Eligible study subjects include adults who are candidates for curative intent sphincter-sparing surgery and who lack high-risk features, particularly tumor encroaching upon the mesorectal fascia (within 3 mm) as determined by pre-treatment endoscopic ultrasound (EUS) and/or magnetic resonance imaging (MRI) or distal rectal tumors (\<5 cm from the anal verge).

Pelvic Radiotherapy With Concurrent Neoadjuvant FOLFOX for Patients With Newly Diagnosed Rectal Adenocarcinoma

Phase II Trial of Low Dose Whole Pelvic Radiotherapy With Concurrent Neoadjuvant FOLFOX for Patients With Newly Diagnosed T3N0M0, T2N1M0, or T3N1M0 Rectal Adenocarcinoma

Overall survival rate of patients who receive a neoadjuvant full dose FOLFOX plus the addition of concurrent LDFRT result in a pCR response rate of at least 35%.

Number of adverse events caused from the administration of neoadjuvant concurrent LDFRT-FOLFOX while maintaining a high rate of pelvic R0 resection compared to standard preoperative chemoradiation and total mesorectal excision surgery.

University of Maryland, Baltimore

Principal Investigator

Part I:

FOLFOX: combination of drugs administered in a specific sequence as prescribed below.

* Oxaliplatin: 85 mg/m2 intravenously (IV) over 2 hours
* Leucovorin: 200 mg/m2 IV bolus over 2 hours
* 5-FU: 400 mg/m2 IV bolus over 5-15 minutes, then 2,400 mg/m2 continuous IV infusion over 46-48 hours

Part II:

Low dose fractionated radiation therapy (LDFRT) Intensity-modulated, bone marrow sparing, whole pelvic radiation therapy 40 cGy fractions twice per day delivered at least 4-6 hours apart on the first 2 days of each chemotherapy cycle for a total of 6 cycles

FOLFOX {5-fluorouracil (5-FU), leucovorin, and oxaliplatin}: see arm description

Low dose fractionated radiation therapy (LDFRT): see arm description

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Low Dose Radiation Therapy for Glioblastoma Multiforme	NCT01466686	High Grade Glio...	Low Dose Fracti... Temozolomide	18 Years - 100 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Low Dose Radiation Therapy for Glioblastoma Multiforme	NCT01466686	High Grade Glio...	Low Dose Fracti... Temozolomide	18 Years - 100 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Pelvic Radiotherapy With Concurrent Neoadjuvant FOLFOX for Patients With Newly Diagnosed Rectal Adenocarcinoma	NCT02319304	Rectal Adenocar...	FOLFOX {5-fluor... Low dose fracti...	18 Years -	University of Maryland, Baltimore
Pelvic Radiotherapy With Concurrent Neoadjuvant FOLFOX for Patients With Newly Diagnosed Rectal Adenocarcinoma	NCT02319304	Rectal Adenocar...	FOLFOX {5-fluor... Low dose fracti...	18 Years -	University of Maryland, Baltimore
Pelvic Radiotherapy With Concurrent Neoadjuvant FOLFOX for Patients With Newly Diagnosed Rectal Adenocarcinoma	NCT02319304	Rectal Adenocar...	FOLFOX {5-fluor... Low dose fracti...	18 Years -	University of Maryland, Baltimore
Pelvic Radiotherapy With Concurrent Neoadjuvant FOLFOX for Patients With Newly Diagnosed Rectal Adenocarcinoma	NCT02319304	Rectal Adenocar...	FOLFOX {5-fluor... Low dose fracti...	18 Years -	University of Maryland, Baltimore

Spots Global Cancer Trial Database for low dose fractionated radiation therapy (ldfrt)