Neoplasms

Digestive System Diseases

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Antineoplastic Agents

All Drugs and Chemicals

Oxaliplatin

Fluorouracil

Irinotecan

Capecitabine

Folfirinox

Antimetabolites

Topoisomerase I Inhibitors

Enzyme Inhibitors

All participants will receive the FOLFIRINOX regimen, followed by capecitabine and short course radiation therapy.

FOLFIRINOX

Short Course Radiation

1-4 weeks after completion of capecitabine therapy

Surgery

Theodore S Hong, M.D.

This research study is a Phase II clinical trial. Phase II clinical trials test the effectiveness of a therapy to learn whether the therapy works in treating a specific cancer. "Investigational" means that the therapy is still being studied and that research doctors are trying to find out more about it-such as the safest dose to use, the side effects it may cause, and if therapy is effective for treating different types of cancer. Proton beam radiation therapy is an FDA (U.S. Food and Drug Administration) approved radiation delivery system.

Proton beam radiation therapy is known to spare surrounding normal tissues from radiation as it delivers less radiation beyond the area of the target tissues. This may reduce side effects that patients would normally experience with standard (photon) radiation therapy, which tends to include more normal tissue along with tumor target tissue.

Researchers in the laboratory have discovered that there are pathways inside the cells that can lead to growth and survival of the tumor. The chemotherapy drugs FOLFIRINOX and capecitabine are targeted towards blocking the pathways that allow cancer cells to divide, and may result in the tumor shrinking in size.

In this research study, the investigators are looking to determine if proton beam radiation in combination with FOLFIRINOX and capecitabine is effective in controlling the growth of your cancer.

For weeks 1-8, you will only be receiving FOLFIRINOX via IV infusion. The treatment plan will begin with four cycles (8 weeks) of FOLFIRINOX. Each cycle is 14 days long. You will receive FOLFIRINOX therapy on days 1, 2 and 3 of each of the four cycles. The FOLFIRINOX treatment is broken up into three different drugs. 5-FU will be administered over two hours on day one of each cycle, and then continuously with a pump for days 2 and 3. Oxaliplatin will be delivered by intravenous (infusion) over 120 minutes. Irinotecan will be given by IV for 90 minutes. All parts of this treatment will be received as an outpatient.

If after 4 cycles of FOLFIRINOX therapy, your tumor has not spread, you will receive a further 4 cycles of FOLFIRINOX. If after 8 total cycles of FOLFIRINOX your cancer is clearly resectable, you will proceed to phase 2 of treatment with capecitabine and radiation therapy.

You will take tablets of capecitabine by mouth for a total of 10 days (Monday through Friday) during the two weeks after your FOLFIRINOX treatment.

You will be given a drug diary for capecitabine which contains instructions on how to take the drug.

Short course radiation: You will receive proton radiation treatment for five days (Monday through Friday) after your FOLFIRINOX treatment, during the time of your capecitabine treatment, or photon radiation for ten days (Monday through Friday for two weeks). You will also be assessed at least once during this treatment course for any side effects you may be experiencing.

You will receive study radiation treatment as an outpatient at the Francis H. Burr Proton Center or the Clark Center for Radiation Oncology at the Massachusetts General Hospital Surgery is expected to occur approximately one to four weeks after completion of capecitabine therapy.

After your surgery, you may receive additional chemotherapy at the discretion of your treating physician and be followed as per standard of care.

FOLFIRINOX + RT for Pancreatic Cancer

Phase II Study of Preoperative FOLFIRINOX Followed by Accelerated Short Course Radiation Therapy for Borderline-Resectable Pancreatic Cancer

The rate of R0 resection of patients with borderline-resectable adenocarcinoma of the head of the pancreas, along with borderline-resectable and resectable adenocarcinoma of the body and tail of the pancreas. R0 resection means that following surgery, no cancer cells are seen microscopically at the resection margin.

The median progression free survival as measured from the start of treatment until the time of disease progression or death, whichever occurs first. Disease status was evaluated using RECIST (Response Evaluation Criteria in Solid Tumors). Disease progression is defined as having at least a 20% increase in the sum of the longest diameter (LD) of target lesion, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Median overall survival, as measured from the start of treatment until the time of death.

Frequency of grade 3 or greater adverse events deemed related to FOLFIRINOX+short course radiation therapy. Adverse events were assessed using Common Terminology Criteria for Adverse Events (CTCAE 4).

The number of participants with surgery related any grade adverse events following pancreaticoduodenectomy or distal pancreatectomy after receiving preoperative FOLFIRINOX and preoperative short course radiation therapy. Adverse events were assessed using Common Terminology Criteria for Adverse Events (CTCAE 4).

The number of participants that died within 30 days after undergoing pancreaticoduodenectomy or distal pancreatectomy.

To determine the rate of pathologic down-staging among participants that underwent pancreaticoduodenectomy or distal pancreatectomy. The pathologic downstaging rate is the proportion of patients with the primary tumor and nodes downstaged based on final pathology of the surgical specimen.

The number of participants that achieved local control. Local control was evaluated using RECIST (Response Evaluation Criteria in Solid Tumors). Local Failure is defined as progression of the primary tumor, or to the reappearance of tumor at the primary site.

To correlate mutational analysis biomarkers (SNaPSHOT assay) with response to treatment

Patient-reported outcomes: We will use descriptive statistics to describe Quality of Life (QOL) (EORTC QLQ-C30), symptom burden (ESAS-r) and mood (HADS) for the entire study cohort.

Summary of the number of hospitalizations, intensive care unit (ICU) stays, emergency department (ED) stays, and palliative care use for the study population.

National Cancer Institute (NCI)

Massachusetts General Hospital

Principal Investigator

Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment

All participants will receive the FOLFIRINOX regimen, followed by capecitabine and short course radiation therapy.

FOLFIRINOX: Up to Eight-14 day cycles

Capecitabine: Orally, for 10 days

Short Course Radiation: Five or ten days

Surgery: 1-4 weeks after completion of capecitabine therapy

FOLFIRINOX + Radiation

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

United States

Region of Enrollment

<35 U/ml (Normal)

≥35 U/ml (elevated)

CA19-9 Level

CEA Level

Head

Body

Tail

Pancreatic Tumor Site

Tumor Size

Vessel Involvement

Dr. Theodore Hong

The overall study population

All participants will receive the FOLFIRINOX regimen, followed by capecitabine and short course radiation therapy.

FOLFIRINOX: Up to Eight-14 day cycles

Capecitabine: Orally, for 10 days

Short Course Radiation: Five or ten days

Surgery: 1-4 weeks after completion of capecitabine therapy

All Eligible - FOLFIRINOX + Radiation

The participants that were resected.

All participants will receive the FOLFIRINOX regimen, followed by capecitabine and short course radiation therapy.

FOLFIRINOX: Up to Eight-14 day cycles

Capecitabine: Orally, for 10 days

Short Course Radiation: Five or ten days

Surgery: 1-4 weeks after completion of capecitabine therapy

Resected Participants - FOLFIRINOX + Radiation

Rate of R0 Resection

Median Progression-Free Survival

Median Overall Survival

Diarrhea

Neutropenia

Febrile neutropenia

Lymphopenia

Thrombocytopenia

Anemia

Elevated alkaline phosphatase

Elevated bilirubin

Elevated AST/ALT

Peripheral neuropathy

Abdominal pain

Constipation

Preoperative Toxicity of Grade 3 or Worse Related to FOLFIRINOX and Chemoradiation

The Proportion of Participants With Surgery Related Adverse Events

The number of participants that underwent surgery

30 Day Post-operative Mortality Rate

Rate of Pathologic Downstaging

The first 5 participants treated who only received 4 cycles of FOLFIRINOX instead of 8 were not included in the analysis of local control.

Local Control Rates

Correlation of Mutational Analysis Biomarkers

Quality of Life, Symptom Burden, and Mood

Utilization of Health Services (Emergency Room, Hospital and Intensive Care Unit)

Overall Study

Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Intestinal Diseases

Rectal Diseases

Antibodies

Antibodies, Monoclonal

Niraparib

Dostarlimab

Immunoglobulins

Poly(ADP-ribose) Polymerase Inhibitors

niraparib, 100 mg orally once daily for up to 12 weeks dostarlimab, 500 mg infused (IV) once every 3 weeks for up to 12 weeks radiation therapy, 5 Gray (Gy) per day for 5 consecutive days

niraparib, 200 mg orally once daily for up to 12 weeks dostarlimab, 500 mg infused (IV) once every 3 weeks for up to 12 weeks radiation therapy, 5 Gray (Gy) per day for 5 consecutive days

Niraparib is a drug FDA-approved for use in maintenance treatment of adults with advanced ovarian cancer, fallopian tube cancer, or primary peritoneal cancer.

Dostarlimab, sold under the brand name Jemperli, is a monoclonal antibody medication used for the treatment of endometrial cancer.

Participants will be treated with intensity modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) to minimize mean dose to femoral, pelvic, and lumbar bone marrow. The entire mesorectum will be treated to a total dose of 25 Gy.

Short course radiation

Joseph M. Caster, M.D., Ph.D.

Saima Sharif, M.D.

Sandy Vollstedt, RN, BSN, OCN

Heather Brown, RN, BAN, OCN

Joseph M Caster, MD, PhD

Saima Sharif, MD

Joseph Cullen, MD, FACS

This clinical trial is designed to determine the maximum tolerated dose of niraparib when combined with dostarlimab and hypofractionated radiation for locally advanced rectal cancer. Once this is determined, this dose will be tested to identify what impact it has on the tumor as well as patient reported outcome measures.

Standard of care therapy for resectable locally advanced rectal cancer includes pelvic radiation (short or long course), chemotherapy, and (if indicated) surgery.

In this study, participants will:

* Take niraparib by mouth once daily for up to 12 weeks.
* Receive radiation therapy once daily for five days (Monday through Friday).
* Receive intravenous (IV) dostarlimab once every three weeks for up to 12 weeks.
* Provide feedback about how they feel and their quality of life. This is done through short surveys as well as discussing with the study team.
* Undergo a sigmoidoscopy (i.e. scope of the tumor) and biopsy about halfway through treatment
* Provide tumor tissue and blood samples for analysis

A Safety Study Adding Niraparib and Dostarlimab to Radiation Therapy for Rectal Cancers

A Phase 1b/2 Trial of Preoperative Niraparib, Dostarlimab, and Hypofractionated Radiotherapy for the Treatment of Locally-advanced Rectal Cancers.

Data will be released publicly as per participant consent and IRB approval. Individual researchers should contact the research team for data sharing.

The recommended dose will be determined by incidence of dose limiting toxicities.

Clinical evaluation of the tumor by both flexible sigmoidoscopy and pelvic MRI

Time from treatment day 1 to death from any cause

Time (measured in days) to documented disease progression in imaging as described by the RECIST criteria.

Time (measured in days) to documented disease progression outside of the pelvis or death from any cause.

Time (measured in days) to disease progression within the pelvis or death from any cause.

Time (measured in days) to receipt of permanent ostomy or death from any cause.

Objective response rate, measured using the standardized RECIST criteria, is a reflection of complete tumor response and partial tumor response. The

Absence of viable tumor in the primary tumor bed and all regional nodes in patients recommended to undergo surgical resection regardless of response to neoadjuvant therapy.

Organ perservation defined as day 1 therapy to receipt of rectal resection for any reason

GlaxoSmithKline

Joseph Caster, Ph.D., M.D.

Assistant Professor

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Micronutrients

Leucovorin

Immunomodulating Agents

1. Week 1: D1-5: radiotherapy 25 Gy in 5 fractions
2. mFOLFOX-6: Oxaliplatin 85 mg/m2 in a 2-hour infusion Leucovorin 400 mg/m² over 2 hours Bolus fluorouracil 400 mg/m² followed by a 48-hour infusion of fluorouracil 2,400 mg/m² + COMPOUND 2055269 10 mg/kg every 2 weeks (first administration at D15, for a total of 6 cycles)
3. Week 16 or 17 (2 to 3 weeks after last cycle of chemotherapy + COMPOUND 2055269): Total Mesorectal Excision

COMPOUND 2055269 to be given every 2 weeks with chemotherapy for 6 cycles

COMPOUND 2055269

Radiotherapy 25 Gy to be given on Days 1-5

Radiation Therapy

mFOLFOX

Surgery to be done 2-3 weeks after last cycle of chemotherapy and COMPOUND 2055269

Total Mesorectal Excision

Ali I Shamseddine, M.D.

The purpose of this study is to show that the addition of COMPOUND 2055269, an immunotherapeutic drug, to Folfox chemotherapy will improve the pathologic complete response rate in patients with locally advanced rectal cancer.

The purpose of this study is to show that the addition of COMPOUND 2055269, an immunotherapeutic drug, to Folfox chemotherapy will improve the pathologic complete response rate in patients with locally advanced rectal cancer.

COMPOUND 2055269 has demonstrated meaningful clinical activity across various tumor types and treatment settings. No clinical trial is conducted over COMPOUND 2055269 in locally-advanced rectal adenocarcinoma.

Short-course Radiation Followed by mFOLFOX-6 Plus COMPOUND 2055269 for Locally-advanced Rectal Adenocarcinoma

Will be done via pathologic assessment on the surgical specimen

1) Progression free survival is measured by imaging and serial tumor markers during follow up visits

2) PD-L1 \& T cell infiltration is measured by a pathology assessment on day 10 and after surgery

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
FOLFIRINOX + RT for Pancreatic Cancer	NCT01591733	Pancreatic Canc...	FOLFIRINOX Capecitabine Short Course Ra... Surgery	18 Years -	Massachusetts General Hospital
A Safety Study Adding Niraparib and Dostarlimab to Radiation Therapy for Rectal Cancers	NCT04926324	Rectal Neoplasm... Rectal Neoplasm...	Niraparib Dostarlimab Short course ra...	18 Years -	University of Iowa
FOLFIRINOX + RT for Pancreatic Cancer	NCT01591733	Pancreatic Canc...	FOLFIRINOX Capecitabine Short Course Ra... Surgery	18 Years -	Massachusetts General Hospital
Short-course Radiation Followed by mFOLFOX-6 Plus COMPOUND 2055269 for Locally-advanced Rectal Adenocarcinoma	NCT03503630	Locally Advance...	COMPOUND 205526... Radiation Thera... mFOLFOX Total Mesorecta...	18 Years -	American University of Beirut Medical Center
Short-course Radiation Followed by mFOLFOX-6 Plus COMPOUND 2055269 for Locally-advanced Rectal Adenocarcinoma	NCT03503630	Locally Advance...	COMPOUND 205526... Radiation Thera... mFOLFOX Total Mesorecta...	18 Years -	American University of Beirut Medical Center

Spots Global Cancer Trial Database for short course radiation