Rectal CancerPhase 1/2NCT02010567
Neoadjuvant Chemoradiotherapy With CRLX-101 and Capecitabine for Rectal Cancer
A Phase 1/2 study testing CRLX101, Capecitabine and Radiotherapy in people with Rectal Cancer, run by UNC Lineberger Comprehensive Cancer Center at 6 sites in United States.
Trial summary
This trial will enroll patients with locally advanced rectal cancer (resectable and non-resectable).The phase Ib dose escalation portion of trial is designed to determine the maximum tolerated dose (MTD) of CRLX101 when combined with standard neoadjuvant therapies capecitabine (Cape) and radiation therapy (XRT). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rectal Cancer
- What is being tested?
- CRLX101, Capecitabine and Radiotherapy
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 6 sitesUnited States
- Study dates
- Dec 2013to 25 Jun 2019
- Phase
- Phase 1/2
- 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
- Eastern Cooperative Oncology Group (ECOG) performance score ≤ 2
- Phase Ib and II: surgical candidates, with moderate to high-risk pathologically-confirmed rectal cancer (Tumor (T) and Nodal (N) stage cT3-4N0 or cT1-4N+); clinical staging by endoscopic ultrasound (EUS) or magnetic resonance imaging (MRI) is permitted.
- Phase Ib only:
- Patients with metastatic rectal cancer are allowed if their primary site meets other eligibility criteria and chemoradiotherapy is recommended as initial therapy for symptom palliation by the multidisciplinary treating team
- Patients with locally advanced unresectable rectal cancer are allow provided:
- There is no evidence of recto-vaginal, recto-vesicular, recto-intestinal fistulization
Show all 13Show fewer
- Standard dose and schedule chemoradiotherapy is recommended as initial therapy by the multidisciplinary treating team
- Age ≥18 years old
- Women of childbearing potential (WOCBP) must have negative pregnancy test within 7 days prior to D1 of treatment
- Recommendation to undergo concurrent chemoradiation, as determined by the treating physician
- Ability to swallow oral medications
- As determined by the enrolling physician or protocol designee, ability of the patient to understand and comply with study procedures for the entire length of the study
- Informed consent reviewed and signed
Who cannot join
- Patients meeting any of the following exclusion criteria will not be able to participate in this study:
- Grade 2 or higher diarrhea at baseline unless deemed by the investigator to be caused by laxatives prescribed for symptomatic partial obstruction (e.g. MiraLAX®)
- Not deemed a candidate for concurrent chemoradiation for medical reasons, such as uncontrolled infection (including HIV), uncontrolled diabetes mellitus or cardiac disease which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient.
- Specific laboratory exclusion values, including:
- Hemoglobin < 10.0 g/dL for males and ≤ 9.0 g/dL for females (transfusion allowed to achieve or maintain levels)
- Absolute neutrophil count (ANC) < 1,500/mm3
Show all 20Show fewer
- Platelet count < 100,000/mm3
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 2.5 times upper level of normal (ULN)
- Alkaline phosphatase > 2.5 times ULN
- Total bilirubin > 1.5 times ULN
- Creatinine clearance < 50 mL/min
- International normalized ratio (INR) >2
- Known dihydropyrimidine dehydrogenase (DPD) deficiency
- History of Gilbert's syndrome
- Those who require therapeutic anticoagulation with coumarin-derivative anticoagulants
- Unable to provide informed consent
- Receiving any other concurrent cytotoxic, biologic agent(s) or investigational agent
- Patients with a "currently active" second malignancy other than non-melanoma skin cancers, non-invasive bladder cancer, "low risk" adenocarcinoma of the prostate and carcinoma in situ of the cervix. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for ≥ 2 years.
- Previous pelvic radiation therapy
- Prior treatment with a topoisomerase I inhibitor (i.e. irinotecan, topotecan)
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
University of North Carolina
Chapel Hill, North Carolina, 27599
Rocky Mountain Cancer Center
Denver, Colorado, 80218
Indiana University Simon Cancer Center
Indianapolis, Indiana, 46202
Rex Cancer Center at Rex Hospital
Raleigh, North Carolina, 27607
Swedish Cancer Institute
Seattle, Washington, 98104
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, 27157
About this study
Official title: Phase Ib/II Study of Neoadjuvant Chemoradiotherapy With CRLX-101 and Capecitabine for Locally Advanced Rectal Cancer
This trial will enroll patients with locally advanced rectal cancer (resectable and non-resectable).The phase Ib dose escalation portion of trial is designed to determine the maximum tolerated dose (MTD) of CRLX101 when combined with standard neoadjuvant therapies capecitabine (Cape) and radiation therapy (XRT). CRLX101 is a nanopharmaceutical (NP) formulation of camptothecin. These results will determine the recommended phase II dose (RP2D) for CRLX101 in this setting. The phase II portion of the trial is designed to evaluate the efficacy and safety of CRLX101 at the RP2D, when combined with capecitabine and radiation therapy prior to surgery.
Read the detailed description
This is an open label, single-arm, multi-center, Phase Ib/II study designed to evaluate CRLX101, which is a NP formulation of camptothecin, dosed in combination with capecitabine and radiation therapy in patients with advanced rectal carcinoma.
The purpose of the Phase Ib portion of this study is to identify the MTD of CRLX101 when added to standard neoadjuvant chemo-radiotherapy. The MTD will be based on the rate of dose-limiting toxicity (DLT) in Phase Ib, and will be assessed via NCI's CTCAE v4.0 toxicity criteria. The MTD will be assigned as the RP2D in this trial.
If CRLX101 can be safely administered in combination with capecitabine and radiation at doses >/= 9 mg/m^2 IV in the Phase Ib study, then the trial will proceed to Phase II. Patients in the Phase Ib study will be included in the Phase II outcome analyses when applicable. The phase II study is designed to evaluate the efficacy of this regimen by assessing the rate of pathological complete response (pCR) while monitoring safety and tolerability.
We anticipate accrual of up to 25 patients per year for the Phase II study, with a slightly faster accrual of 2-3 patients per month for Phase Ib given the broader inclusion criteria.
During Phase Ib, we will evaluate the safety and determine the MTD/RP2D of CRLX101 + capecitabine (Cape) and radiation therapy (XRT) in patients with rectal cancer using the traditional 3+3 dose escalation design. Adverse events (AEs) will be evaluated via the CTCAE version 4.0. Patients in Phase Ib will also be followed for pathological response if they have resectable disease.
If CRLX101 can be safely administered in combination with capecitabine and radiation at doses >/=9 mg/m^2 IV in the Phase Ib study, then the trial will proceed to Phase II with a primary objective of estimating the rate of pCR. Non-metastatic patients with resectable disease and treated at the MTD/RP2D in Phase Ib will be included in the Phase II study population.
In Phase II, CRLX101 will be administered at the RP2D in combination with capecitabine and radiation in patients with locally advanced rectal cancer for a total of 5-6 weeks, depending on the total radiation dose. A total of 3 doses of CRLX101 will be administered every other week. Surgery will take place at least 6 weeks after the completion of chemoradiotherapy.
For our non-metastatic Phase I patients and our Phase II population, postoperative adjuvant therapy is indicated regardless of whether a pCR is achieved or not. While there are a number of regimens used in the adjuvant setting, national guidelines do not specify one of these regimens over the other. Given the consistent application of adjuvant therapies in this population, we also plan to follow Phase II patients for both disease free survival (DFS) and overall survival (OS).
- Conditions
- Rectal Cancer
- Being tested
- CRLX101, Capecitabine, Radiotherapy, Surgery
- Keywords
- rectal cancer, colorectal cancer, locally advanced rectal cancer, locally advanced rectal cancer (resectable), locally advanced rectal cancer (non-resectable), chemoradiotherapy, nanopharmaceutical, CLRX101, camptothecin, capecitabine
- Medical subject headings
- Rectal Neoplasms, Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CRLX101Drug
CRLX101 is an experimental nanoparticle formulation of the anticancer agent camptothecin manufactured by Cerulean Pharma Inc..
CapecitabineDrug
Also called Xeloda
Capecitabine is an oral fluoropyrimidine pro-drug, metabolically converted to 5-fluorouracil after administration. It is indicated as adjuvant treatment in patients with stage III colorectal cancer (Dukes' C colon cancer), and as first-line treatment of metastatic colorectal cancer.
RadiotherapyRadiation
Also called Intensity Modulated Radiation Therapy, IMRT
This protocol allows physician discretion as to the use of Intensity Modulated Radiation Therapy (IMRT) or 3D conformal planning techniques.
Radiation begins on Day1 of neoadjuvant chemotherapy and continues for 28 (if <T4) or 30 (T4 disease) consecutive weekdays. Patient will receive 1.8 Gy daily fractions of radiotherapy without a break except for weekends and holidays.
Dose is to be prescribed to an isodose surface that encompasses the planning target volume (PTV) and that satisfies the dose uniformity guidelines below. The minimum dose to PTV 1 and PTV 2 shall be no less than 95% of the protocol specified dose for that volume.
SurgeryProcedure or surgery
Also called Resection, Surgical resection
Surgery will take place at least 6 weeks post completion of chemoradiotherapy in patients with resectable disease; tissue from surgical resection will be preserved for correlative studies in those patients who do not achieve a pCR.
| Study group | Role | What they receive |
|---|---|---|
| CLRX101 MTD/RP2D | Experimental | During Phase Ib, we will evaluate the safety and determine the MTD/RP2D of CRLX101 + capecitabine (Cape) and radiation therapy (XRT) in patients with rectal cancer using the traditional 3+3 dose escalation design. Adverse events (AEs) will be evaluated via the CTCAE version 4.0. Patients in Phase Ib will also be followed for pathological response if they have resectable disease. Receives: Drug: CRLX101; Drug: Capecitabine; Radiation: Radiotherapy |
| Chemoradiotherapy + Surgery | Experimental | In Phase II, CRLX101 will be administered at the RP2D in combination with capecitabine and radiation in patients with locally advanced rectal cancer for a total of 5-6 weeks, depending on the total radiation dose. A total of 3 doses of CRLX101 will be administered every other week. Surgery will take place at least 6 weeks after the completion of chemoradiotherapy. Receives: Drug: CRLX101; Drug: Capecitabine; Radiation: Radiotherapy; Procedure: Surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of CRLX101 When Added to Standard Neoadjuvant Chemoradiotherapy Consisting of Capecitabine + Radiotherapy in Locally Advanced Rectal Cancer
The MTD is the highest dose of CRLX101 at which ≤1 out of 6 patients had a dose limiting toxicity (DLT) using CTCAE v4.0 toxicity criteria. DLTs include Grade (G) >3 neutropenia for ≥7 days; G 3 or 4 neutropenia with fever; G 4 anemia not related to cancer-associated bleeding; G 4 thrombocytopenia or G 3 with clinically significant bleeding; G ≥3 nausea or vomiting >48 hours despite anti-emetics; G 2 cystitis not resolved within 14 days; second G 2 cystitis; G 3 or 4 cystitis; diarrhea requiring dose reduction; Any other non-hematologic toxicity G ≥3 requiring a dose reduction (G ≥3 infusion-related reactions were not a DLT unless they recur despite slowing down the infusion); Other CRLX101 related treatment emergent adverse effect (TEAE) that requires patient withdrawal prior to completing all doses; Radiotherapy interruption due to TEAEs ≥5 days; or Dose interruption or reduction of capecitabine due to TEAE that results in <50% of the scheduled capecitabine dose for entire course
Measured: 12 weeks
Pathological Complete Response (pCR) Rate
Primary Objective Phase II: Pathological response will be made based on microscopic assessment of the surgical specimen at the primary treatment site. A pCR must include no gross or microscopic tumor identified anywhere within the surgical specimen. This must include:No evidence of malignant cells in the primary tumor specimen and No lymph nodes that contain tumor.
Measured: 12 weeks
Secondary outcomes (6)
Pathological Response Rate
Pathologic response will be made based on microscopic assessment of the surgical specimen at the primary treatment site, including regional nodes and any peritumoral satellite nodules in the specimen, and categorized as outlined below as per the American Joint Committee on Cancer (AJCC) Cancer Staging Manual 7th edition.Determination of pathological response will be reported by the local pathologist.
- Pathologic Complete Response (pCR): No gross or microscopic tumor identified anywhere within the surgical specimen. This must include: No evidence of malignant cells in the primary tumor specimen and No lymph nodes that contain tumor.
- Moderate response: Single cells or small groups of cancer cells
- Minimal response: Residual cancer outgrown by fibrosis
- Poor response:Minimal or no tumor kill; extensive residual cancer
Measured: 12 weeks
Number of Participants With Grade 3 or Higher, Treatment-related Toxicities
Toxicity profile of CRLX101 when combined with capecitabine + radiotherapy to treat patients with locally advanced rectal cancer. Phase Ib and Phase II - Safety is the reported adverse event (AE) profile characterized by NCI CTCAE v4.0. The profile was limited to grade 3 or higher, treatment related AEs.
Measured: 12 weeks
Disease-free Survival (DFS) Rate
Phase II only - DFS will be defined as the time from surgical resection until disease recurrence or death as a result of any cause, reported as the count of participants still alive without recurrence at the end of study follow-up.
Measured: An average of 2.6 years (full range 2.1 to 3.1 years)
Overall Survival (OS) Rate
Phase II only - OS is defined as the time from surgical resection until death reported as the count of participants still alive at the end of study follow-up.
Measured: an average of 2.6 years (full range 2.1 to 3.1 years)
Disease-free Survival (DFS) Rate Based on Pathological Complete Response (pCR).
Phase II only - a comparison of DFS for patients who achieve pCR and those who do not. DFS will be defined as the time from surgical resection until disease recurrence or death as a result of any cause, reported as the count of participants still alive without recurrence at the end of study follow-up.
Measured: an average of 2.6 years (full range 2.1 to 3.1 years)
Overall Survival (OS) Based on Pathological Complete Response (pCR).
Phase II only - a comparison of OS for patients who achieve pCR and those who do not. OS is defined as the time from surgical resection until death reported as the count of participants still alive at the end of study follow-up.
Measured: an average of 2.6 years (full range 2.1 to 3.1 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2013 (estimated)
- Study startDec 2013
- Primary completion16 Sep 2016
- Study completion25 Jun 2019
Why it stopped: The study was halted prematurely at the funding partner's request.
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.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Rectal CancerStudies of the same condition, open and under way.
- More trials run by UNC Lineberger Comprehensive Cancer CenterThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- UNC Lineberger Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Cerulean Pharma Inc.
- Responsible party
- Sponsor
- Investigators
- Andrew Wang, MD, Principal investigator, UNC Lineberger Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02010567
- Sponsor's protocol ID
- LCCC 1315
- Status last verified
- Oct 2020
- First submitted
- 9 Dec 2013
- Last updated
- 3 Nov 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Sanoff HK, Moon DH, Moore DT, Boles J, Bui C, Blackstock W, O'Neil BH, Subramaniam S, McRee AJ, Carlson C, Lee MS, Tepper JE, Wang AZ. Phase I/II trial of nano-camptothecin CRLX101 with capecitabine and radiotherapy as neoadjuvant treatment for locally advanced rectal cancer. Nanomedicine. 2019 Jun;18:189-195. doi: 10.1016/j.nano.2019.02.021. Epub 2019 Mar 8.
PubMed 30858085Tian X, Nguyen M, Foote HP, Caster JM, Roche KC, Peters CG, Wu P, Jayaraman L, Garmey EG, Tepper JE, Eliasof S, Wang AZ. CRLX101, a Nanoparticle-Drug Conjugate Containing Camptothecin, Improves Rectal Cancer Chemoradiotherapy by Inhibiting DNA Repair and HIF1alpha. Cancer Res. 2017 Jan 1;77(1):112-122. doi: 10.1158/0008-5472.CAN-15-2951. Epub 2016 Oct 26.
PubMed 27784746
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ib/II Study of Neoadjuvant Chemoradiotherapy With CRLX-101 and Capecitabine for Locally Advanced Rectal Cancer
- ClinicalTrials.gov ID
- NCT02010567
- Acronym / sponsor ID
- LCCC 1315
- Conditions
- Rectal Cancer
- Keywords
- rectal cancer, colorectal cancer, locally advanced rectal cancer, locally advanced rectal cancer (resectable), locally advanced rectal cancer (non-resectable), chemoradiotherapy, nanopharmaceutical, CLRX101
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was halted prematurely at the funding partner's request.
- Enrolment
- 32 participants (actual)
- Lead sponsor
- UNC Lineberger Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- Cerulean Pharma Inc.
- Study start
- Dec 2013
- Primary completion
- 16 Sep 2016 (actual)
- Study completion
- 25 Jun 2019 (actual)
- First posted
- 12 Dec 2013 (estimated)
- Results
- Posted 14 Nov 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This trial will enroll patients with locally advanced rectal cancer (resectable and non-resectable).The phase Ib dose escalation portion of trial is designed to determine the maximum tolerated dose (MTD) of CRLX101 when combined with standard neoadjuvant therapies capecitabine (Cape) and radiation therapy (XRT). CRLX101 is a nanopharmaceutical (NP) formulation of camptothecin. These results will determine the recommended phase II dose (RP2D) for CRLX101 in this setting. The phase II portion of the trial is designed to evaluate the efficacy and safety of CRLX101 at the RP2D, when combined with capecitabine and radiation therapy prior to surgery.
Detailed description
This is an open label, single-arm, multi-center, Phase Ib/II study designed to evaluate CRLX101, which is a NP formulation of camptothecin, dosed in combination with capecitabine and radiation therapy in patients with advanced rectal carcinoma.
The purpose of the Phase Ib portion of this study is to identify the MTD of CRLX101 when added to standard neoadjuvant chemo-radiotherapy. The MTD will be based on the rate of dose-limiting toxicity (DLT) in Phase Ib, and will be assessed via NCI's CTCAE v4.0 toxicity criteria. The MTD will be assigned as the RP2D in this trial.
If CRLX101 can be safely administered in combination with capecitabine and radiation at doses >/= 9 mg/m^2 IV in the Phase Ib study, then the trial will proceed to Phase II. Patients in the Phase Ib study will be included in the Phase II outcome analyses when applicable. The phase II study is designed to evaluate the efficacy of this regimen by assessing the rate of pathological complete response (pCR) while monitoring safety and tolerability.
We anticipate accrual of up to 25 patients per year for the Phase II study, with a slightly faster accrual of 2-3 patients per month for Phase Ib given the broader inclusion criteria.
During Phase Ib, we will evaluate the safety and determine the MTD/RP2D of CRLX101 + capecitabine (Cape) and radiation therapy (XRT) in patients with rectal cancer using the traditional 3+3 dose escalation design. Adverse events (AEs) will be evaluated via the CTCAE version 4.0. Patients in Phase Ib will also be followed for pathological response if they have resectable disease.
If CRLX101 can be safely administered in combination with capecitabine and radiation at doses >/=9 mg/m^2 IV in the Phase Ib study, then the trial will proceed to Phase II with a primary objective of estimating the rate of pCR. Non-metastatic patients with resectable disease and treated at the MTD/RP2D in Phase Ib will be included in the Phase II study population.
In Phase II, CRLX101 will be administered at the RP2D in combination with capecitabine and radiation in patients with locally advanced rectal cancer for a total of 5-6 weeks, depending on the total radiation dose. A total of 3 doses of CRLX101 will be administered every other week. Surgery will take place at least 6 weeks after the completion of chemoradiotherapy.
For our non-metastatic Phase I patients and our Phase II population, postoperative adjuvant therapy is indicated regardless of whether a pCR is achieved or not. While there are a number of regimens used in the adjuvant setting, national guidelines do not specify one of these regimens over the other. Given the consistent application of adjuvant therapies in this population, we also plan to follow Phase II patients for both disease free survival (DFS) and overall survival (OS).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CLRX101 MTD/RP2D | Experimental | Drug: CRLX101, Drug: Capecitabine, Radiation: RadiotherapyDuring Phase Ib, we will evaluate the safety and determine the MTD/RP2D of CRLX101 + capecitabine (Cape) and radiation therapy (XRT) in patients with rectal cancer using the traditional 3+3 dose escalation design. Adverse events (AEs) will be evaluated via the CTCAE version 4.0. Patients in Phase Ib will also be followed for pathological response if they have resectable disease. |
| Chemoradiotherapy + Surgery | Experimental | Drug: CRLX101, Drug: Capecitabine, Radiation: Radiotherapy, Procedure: SurgeryIn Phase II, CRLX101 will be administered at the RP2D in combination with capecitabine and radiation in patients with locally advanced rectal cancer for a total of 5-6 weeks, depending on the total radiation dose. A total of 3 doses of CRLX101 will be administered every other week. Surgery will take place at least 6 weeks after the completion of chemoradiotherapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Eastern Cooperative Oncology Group (ECOG) performance score ≤ 2
- Phase Ib and II: surgical candidates, with moderate to high-risk pathologically-confirmed rectal cancer (Tumor (T) and Nodal (N) stage cT3-4N0 or cT1-4N+); clinical staging by endoscopic ultrasound (EUS) or magnetic resonance imaging (MRI) is permitted.
- Age ≥18 years old
- Women of childbearing potential (WOCBP) must have negative pregnancy test within 7 days prior to D1 of treatment
- Recommendation to undergo concurrent chemoradiation, as determined by the treating physician
Key exclusion criteria (20 listed)
- Patients meeting any of the following exclusion criteria will not be able to participate in this study:
- Grade 2 or higher diarrhea at baseline unless deemed by the investigator to be caused by laxatives prescribed for symptomatic partial obstruction (e.g. MiraLAX®)
- Not deemed a candidate for concurrent chemoradiation for medical reasons, such as uncontrolled infection (including HIV), uncontrolled diabetes mellitus or cardiac disease which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient.
- Specific laboratory exclusion values, including:
- Known dihydropyrimidine dehydrogenase (DPD) deficiency
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 |
|---|---|---|
| CRLX101CRLX101 is an experimental nanoparticle formulation of the anticancer agent camptothecin manufactured by Cerulean Pharma Inc.. | Drug | CLRX101 MTD/RP2D, Chemoradiotherapy + Surgery |
| CapecitabineAlso: XelodaCapecitabine is an oral fluoropyrimidine pro-drug, metabolically converted to 5-fluorouracil after administration. It is indicated as adjuvant treatment in patients with stage III colorectal cancer (Dukes' C colon cancer), and as first-line treatment of metastatic colorectal cancer. | Drug | CLRX101 MTD/RP2D, Chemoradiotherapy + Surgery |
| RadiotherapyAlso: Intensity Modulated Radiation Therapy, IMRTThis protocol allows physician discretion as to the use of Intensity Modulated Radiation Therapy (IMRT) or 3D conformal planning techniques. Radiation begins on Day1 of neoadjuvant chemotherapy and continues for 28 (if <T4) or 30 (T4 disease) consecutive weekdays. Patient will receive 1.8 Gy daily fractions of radiotherapy without a break except for weekends and holidays. Dose is to be prescribed to an isodose surface that encompasses the planning target volume (PTV) and that satisfies the dose uniformity guidelines below. The minimum dose to PTV 1 and PTV 2 shall be no less than 95% of the protocol specified dose for that volume. | Radiation | CLRX101 MTD/RP2D, Chemoradiotherapy + Surgery |
| SurgeryAlso: Resection, Surgical resectionSurgery will take place at least 6 weeks post completion of chemoradiotherapy in patients with resectable disease; tissue from surgical resection will be preserved for correlative studies in those patients who do not achieve a pCR. | Procedure or surgery | Chemoradiotherapy + Surgery |
Primary outcome
Maximum Tolerated Dose (MTD) of CRLX101 When Added to Standard Neoadjuvant Chemoradiotherapy Consisting of Capecitabine + Radiotherapy in Locally Advanced Rectal Cancer
Time frame: 12 weeks
The MTD is the highest dose of CRLX101 at which ≤1 out of 6 patients had a dose limiting toxicity (DLT) using CTCAE v4.0 toxicity criteria. DLTs include Grade (G) >3 neutropenia for ≥7 days; G 3 or 4 neutropenia with fever; G 4 anemia not related to cancer-associated bleeding; G 4 thrombocytopenia or G 3 with clinically significant bleeding; G ≥3 nausea or vomiting >48 hours despite anti-emetics; G 2 cystitis not resolved within 14 days; second G 2 cystitis; G 3 or 4 cystitis; diarrhea requiring dose reduction; Any other non-hematologic toxicity G ≥3 requiring a dose reduction (G ≥3 infusion-related reactions were not a DLT unless they recur despite slowing down the infusion); Other CRLX101 related treatment emergent adverse effect (TEAE) that requires patient withdrawal prior to completing all doses; Radiotherapy interruption due to TEAEs ≥5 days; or Dose interruption or reduction of capecitabine due to TEAE that results in <50% of the scheduled capecitabine dose for entire course
Pathological Complete Response (pCR) Rate
Time frame: 12 weeks
Primary Objective Phase II: Pathological response will be made based on microscopic assessment of the surgical specimen at the primary treatment site. A pCR must include no gross or microscopic tumor identified anywhere within the surgical specimen. This must include:No evidence of malignant cells in the primary tumor specimen and No lymph nodes that contain tumor.
6 secondary outcomes
Pathological Response Rate
Time frame: 12 weeks
Number of Participants With Grade 3 or Higher, Treatment-related Toxicities
Time frame: 12 weeks
Disease-free Survival (DFS) Rate
Time frame: An average of 2.6 years (full range 2.1 to 3.1 years)
Overall Survival (OS) Rate
Time frame: an average of 2.6 years (full range 2.1 to 3.1 years)
Disease-free Survival (DFS) Rate Based on Pathological Complete Response (pCR).
Time frame: an average of 2.6 years (full range 2.1 to 3.1 years)
Overall Survival (OS) Based on Pathological Complete Response (pCR).
Time frame: an average of 2.6 years (full range 2.1 to 3.1 years)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30858085Sanoff HK, Moon DH, Moore DT, Boles J, Bui C, Blackstock W, O'Neil BH, Subramaniam S, McRee AJ, Carlson C, Lee MS, Tepper JE, Wang AZ. Phase I/II trial of nano-camptothecin CRLX101 with capecitabine and radiotherapy as neoadjuvant treatment for locally advanced rectal cancer. Nanomedicine. 2019 Jun;18:189-195. doi: 10.1016/j.nano.2019.02.021. Epub 2019 Mar 8.
- Derived from this study: PubMed 27784746Tian X, Nguyen M, Foote HP, Caster JM, Roche KC, Peters CG, Wu P, Jayaraman L, Garmey EG, Tepper JE, Eliasof S, Wang AZ. CRLX101, a Nanoparticle-Drug Conjugate Containing Camptothecin, Improves Rectal Cancer Chemoradiotherapy by Inhibiting DNA Repair and HIF1alpha. Cancer Res. 2017 Jan 1;77(1):112-122. doi: 10.1158/0008-5472.CAN-15-2951. Epub 2016 Oct 26.
- Lineberger Comprehensive Cancer Center websiteLink provided by the sponsor.
Related trials for Rectal Cancer
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingObservational study
Pre- and On-treatment Multi-omics Profiling of Locally Advanced Rectal Cancer
Rectal Neoplasms
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 2
Tislelizumab in People With Colorectal Cancer
Colorectal Cancer
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.
Andrew Wang, MD principal investigator
UNC Lineberger Comprehensive Cancer Center
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing CRLX101, Capecitabine and Radiotherapy in people with Rectal Cancer, run by UNC Lineberger Comprehensive Cancer Center at 6 sites 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 13 inclusion and 20 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 3 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 14 Nov 2017). 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?
Maximum Tolerated Dose (MTD) of CRLX101 When Added to Standard Neoadjuvant Chemoradiotherapy Consisting of Capecitabine + Radiotherapy in Locally Advanced Rectal Cancer (time frame: 12 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02010567, which also lists 2 linked publications.
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 3 Nov 2020.