Rectal AdenocarcinomaPhase 2GCC 1314NCT02319304
Pelvic Radiotherapy With Concurrent Neoadjuvant FOLFOX for Patients With Newly Diagnosed Rectal Adenocarcinoma
A Phase 2 study testing FOLFOX {5-fluorouracil (5-FU), leucovorin, and oxaliplatin} and Low dose fractionated radiation therapy (LDFRT) in people with Rectal Adenocarcinoma, run by University of Maryland, Baltimore at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rectal Adenocarcinoma
- What is being tested?
- FOLFOX {5-fluorouracil (5-FU), leucovorin, and oxaliplatin} and Low dose fractionated radiation therapy (LDFRT)
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2015to 5 Oct 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥ 18 years old at diagnosis.
- ECOG Performance Status 0, 1, or 2.
- Biopsy-proven diagnosis of rectal adenocarcinoma.
- Radiographically measurable or clinically evaluable disease by CT scan of chest/abdomen/pelvis with and without contrast ≤ 28 days prior to registration.
- Clinical AJCC 7th edition stage T2N1M0, T3N0M0 or T3N1M0 based on physical examination, CT scan chest/abdomen/pelvis, and pelvic MRI or endorectal ultrasound.
- Preoperative proctoscopy confirming tumor extent as no less than 5 cm and no greater than 12 cm from the anal verge.
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- Evaluation by a surgical oncologist, radiation oncologist, and medical oncologist ≤ 28 days prior to registration.
- Confirmation by a surgeon that the patient is able to undergo a low anterior resection with total mesorectal excision ≤ 28 days prior to registration.
- In the absence of a being treated on a clinical trial, the patient would be recommended to receive neoadjuvant chemoradiation followed by curative intent surgery.
- The following laboratory values obtained ≤ 28 days prior to registration:
- Absolute neutrophil count (ANC) ≥ 1500/mm3.
- Platelet count ≥ 100,000/mm3.
- Hemoglobin > 8.0 g/dL. May transfuse to meet eligibility.
- Total bilirubin ≤ 1.5 x upper limit of normal (ULN).
- SGOT (AST) ≤ 3 x ULN.
- SGPT (ALT) ≤ 3 x ULN.
- Creatinine ≤ 1.5 x ULN.
- Negative pregnancy test (B-HCG) within 7 days prior to registration for women of childbearing potential.
- Did the patient provide study-specific informed consent prior to study entry?
- Willingness to return to the enrolling medical site for all study assessments.
Who cannot join
- Clinical T4 tumor.
- Primary surgeon indicates the need for an abdominal perineal resection (APR) at baseline.
- Previous pelvic RT.
- Autoimmune disease such as scleroderma, lupus, or inflammatory bowel disease.
- Tumor < 3 mm from the mesorectal fascia as seen on MRI or endorectal ultrasound.
- Tumor-induced symptomatic bowel obstruction.
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- Chemotherapy (including hormonal therapy) within the past 5 years from date of registration.
- Other invasive malignancies within past 5 years from date of registration.
- Pregnant or nursing women.
- Men or women of childbearing potential who are unwilling to employ adequate contraception.
- Other co-morbid conditions that, based on the judgment of the physicians obtaining informed consent, would make the patient inappropriate for this study.
- Any conditions that would preclude a patient from completing all study assessments.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II Trial of Low Dose Whole Pelvic Radiotherapy With Concurrent Neoadjuvant FOLFOX for Patients With Newly Diagnosed T3N0M0, T2N1M0, or T3N1M0 Rectal Adenocarcinoma
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.
Read the detailed description
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).
- Conditions
- Rectal Adenocarcinoma
- Being tested
- FOLFOX {5-fluorouracil (5-FU), leucovorin, and oxaliplatin}, Low dose fractionated radiation therapy (LDFRT)
- Keywords
- Pelvic Radiotherapy, Rectal Adenocarcinoma
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FOLFOX {5-fluorouracil (5-FU), leucovorin, and oxaliplatin}Drug
see arm description
Low dose fractionated radiation therapy (LDFRT)Radiation
see arm description
| Study group | Role | What they receive |
|---|---|---|
| Pelvic Radiotherapy With Concurrent Neoadjuvant FOLFOX | Other | 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 Receives: Drug: FOLFOX {5-fluorouracil (5-FU), leucovorin, and oxaliplatin}; Radiation: Low dose fractionated radiation therapy (LDFRT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary Outcome Measure (Overall Survival Rate)
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%.
Measured: 1 year
Secondary outcomes (1)
Secondary Outcome Measure (Number of Adverse Events)
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.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2014 (estimated)
- Study startMar 2015
- Primary completion5 Oct 2018
- Study completion5 Oct 2018
Why it stopped: Slow accrual, PI left instituion
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Rectal AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by University of Maryland, BaltimoreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Maryland, Baltimore
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Department of Radiation Oncology, University of Maryland, Baltimore
- Investigators
- Shahed Badiyan, MD, Principal investigator, UMMC MSGCC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02319304
- Sponsor's protocol ID
- HP-00060641
- Acronym
- GCC 1314
- Status last verified
- Oct 2021
- First submitted
- 10 Dec 2014
- Last updated
- 4 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Low Dose Whole Pelvic Radiotherapy With Concurrent Neoadjuvant FOLFOX for Patients With Newly Diagnosed T3N0M0, T2N1M0, or T3N1M0 Rectal Adenocarcinoma
- ClinicalTrials.gov ID
- NCT02319304
- Acronym / sponsor ID
- GCC 1314 / HP-00060641
- Conditions
- Rectal Adenocarcinoma
- Keywords
- Pelvic Radiotherapy, Rectal Adenocarcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow accrual, PI left instituion
- Enrolment
- 3 participants (actual)
- Lead sponsor
- University of Maryland, BaltimoreUniversity, hospital or other
- Study start
- Mar 2015
- Primary completion
- 5 Oct 2018 (actual)
- Study completion
- 5 Oct 2018 (actual)
- First posted
- 18 Dec 2014 (estimated)
- Results
- Posted 4 Nov 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pelvic Radiotherapy With Concurrent Neoadjuvant FOLFOX | Other | Drug: FOLFOX {5-fluorouracil (5-FU), leucovorin, and oxaliplatin}, Radiation: Low dose fractionated radiation therapy (LDFRT)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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- ≥ 18 years old at diagnosis.
- ECOG Performance Status 0, 1, or 2.
- Biopsy-proven diagnosis of rectal adenocarcinoma.
- Radiographically measurable or clinically evaluable disease by CT scan of chest/abdomen/pelvis with and without contrast ≤ 28 days prior to registration.
- Clinical AJCC 7th edition stage T2N1M0, T3N0M0 or T3N1M0 based on physical examination, CT scan chest/abdomen/pelvis, and pelvic MRI or endorectal ultrasound.
Key exclusion criteria (12 listed)
- Clinical T4 tumor.
- Primary surgeon indicates the need for an abdominal perineal resection (APR) at baseline.
- Previous pelvic RT.
- Autoimmune disease such as scleroderma, lupus, or inflammatory bowel disease.
- Tumor < 3 mm from the mesorectal fascia as seen on MRI or endorectal ultrasound.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FOLFOX {5-fluorouracil (5-FU), leucovorin, and oxaliplatin}see arm description | Drug | Pelvic Radiotherapy With Concurrent Neoadjuvant FOLFOX |
| Low dose fractionated radiation therapy (LDFRT)see arm description | Radiation | Pelvic Radiotherapy With Concurrent Neoadjuvant FOLFOX |
Primary outcome
Primary Outcome Measure (Overall Survival Rate)
Time frame: 1 year
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%.
1 secondary outcome
Secondary Outcome Measure (Number of Adverse Events)
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shahed Badiyan, MD principal investigator
UMMC MSGCC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing FOLFOX {5-fluorouracil (5-FU), leucovorin, and oxaliplatin} and Low dose fractionated radiation therapy (LDFRT) in people with Rectal Adenocarcinoma, run by University of Maryland, Baltimore at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 4 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary Outcome Measure (Overall Survival Rate) (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2021.