Rectal CancerPhase 1NCT02550743
BrUOG 302:BYL719, Capecitabine and Radiation for Rectal Cancer: A Brown University Oncology Research Group Study
A Phase 1 study testing BYL719, Capecitabine and Radiation in people with Rectal Cancer, run by howard safran at 1 site in United States.
Trial summary
The primary goal of this Brown University Oncology Research Group is to determine that a safe dose of BYL719 can be administered with capecitabine and radiation in patients with rectal cancer. Therefore, the threshold of success for this phase I study is to establish safety. 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?
- BYL719, Capecitabine and Radiation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Jun 2016to 16 Nov 2018
- Phase
- Phase 1
- 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
- Patients must have histologically proven adenocarcinoma of the rectum with no evidence of distant metastases.
- The tumor must be clinically Stage II (T3-4 N0) or stage III (N+). Stage of the tumor may be determined by CT scan, endorectal ultrasound or MRI. (For patients receiving chemotherapy prior to protocol chemoradiation, the initial clinical stage applies. CT/MRI/PET should be performed within 2 months of study entry to exclude disease progression.). For the MTD expansion phase only: patients who are stage IV, and in whom it is planned to administer capecitabine and radiation then have a resection of their rectal cancer, are also eligible.
- Measurable disease not required at baseline. Patient's without measurable disease may be enrolled as long as they clinically meet stage II or III criteria or for MTD expansion phase: also stage IV.
- Patients must not have received pelvic radiation for rectal cancer, or prior pelvic radiation for any other malignancy that would prevent the patient from receiving the required radiation treatments for this study. (Patients may receive neoadjuvant chemotherapy prior to study chemoradiation)
- Patients must not have an active concurrent invasive malignancy. Patients with prior malignancies, including invasive colon cancer, are eligible if they are deemed by their physician to be at low risk for recurrence. For example, patients with squamous or basal cell carcinoma of the skin, melanoma in situ, carcinoma of the cervix, or carcinoma in situ of the colon or rectum that have been effectively treated are eligible, even if these conditions were diagnosed within 3 years prior to registration.
- Patients must be > 18 years of age,
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- ECOG performance status 0-1
- Neutrophil Count >1,000/µl, platelets >100,000/µl, total bilirubin < 1.5 x< ULN ULN (except for patients with Gilbert's syndrome who may only be included if total bilirubin is < 3xULN with direct bilirubin within normal range), ALT <2.5xULN, AST < 2.5xULN, creatinine <1.5xULN, fasting plasma glucose < 140 mg/dL and HbA1c < 6.4% (both criteria have to be met), anemia > 9.0g/dL.Potassium, Calcium and Magnesium (corrected for albumin) within normal range or < grade 1 if determined not clinically significant by treating investigator. INR < 1.5
- Patient is able to swallow and retain oral medication.
- Left ventricular ejection fraction within normal >50%
- Signed informed consent and is able to comply with study and/or follow- up procedures.
- QTcF <480 msec
- Patients history of diarrhea has been review and patient has been informed of potential study drug induced diarrhea and management. This must be documented by treating MD. See section 5 for baseline assessments of patient history of diarrhea.
Who cannot join
- Patient has a known hypersensitivity to any of the excipients of BYL719 (alpelisib)
- Suspected or confirmed metastatic disease including CNS involvement. For stage IV patients: CNS involvement.
- Patient with clinically manifest diabetes mellitus, or documented steroid induced diabetes mellitus
- Patient with impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral BYL719 (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection). Patients with colostomies are allowed unless colostomy is for one of the precluded reason above.
- Patient who has not recovered to grade 1 or better (except alopecia) from related side effects of any prior antineoplastic therapy
- Patient who has had systemic therapy within 4 weeks of starting study treatment (6 weeks for nitrosoureas or mitomycin C)
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- Patient who has undergone major surgery ≤ 4 weeks prior to starting study treatment or in the investigators opinion who has not recovered from side effects of such procedure
- Patient has any of the following cardiac abnormalities: A. symptomatic Congestive heart failure i. history of documented congestive heart failure (New York Heart Association functional classification III-IV), documented cardiomyopathy ii. Left Ventricular Ejection Fraction (LVEF) <50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO) B. myocardial infarction < 6 months prior to enrollment C. unstable angina pectoris D. serious uncontrolled cardiac arrhythmia E. symptomatic pericarditis F. QTcF > 480 msec on the screening ECG (using the QTcF formula)
- Patient who is currently receiving medication with a known risk of prolonging the QT interval or inducing Torsades de Pointes (TdP) and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug treatment. To be documented and submitted to BrUOG with registration. Please refer to appendices F and G.
- Patient who has participated in a prior investigational cancer treatment study within 30 days prior to enrollment. This refers to treatment not follow-up.
- Patient is currently receiving warfarin or other coumarin derived anti-coagulant, for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed. To be documented and submitted to BrUOG with registration. Eliquis is allowed.
- Patient is currently receiving treatment with drugs known to be strong inhibitors or inducers of isoenzyme CYP3A. The patient must have discontinued strong inducers for at least one week and must have discontinued strong inhibitors before the start of treatment. Switching to a different medication prior to registration is allowed; (Refer to Section Concomitant Medication, Appendix F and G).
- Patient with known positive serology for human immunodeficiency virus (HIV)
- Patient with any other condition that would, in the Investigator's judgment, preclude patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures, e.g. infection/inflammation, intestinal obstruction, unable to swallow oral medication, social/psychological complications, chronic active hepatitis, severe hepatic impairment etc
- Patients who have other concurrent severe and/or uncontrolled medical conditions that would, in the Treating Physician's judgment, contraindicate patient participation in the individual patient program (eg. active or uncontrolled severe infection, chronic active hepatitis, immuno-compromised, acute or chronic pancreatitis, uncontrolled high blood pressure, interstitial lung disease, etc.)
- Patient has a history of non-compliance to medical regimen or inability to grant consent
- Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL). Pregnancy test not required for patients who are considered post-menopausal and not of childbearing potential as defined below.
- Women are considered post-menopausal and not of child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) at least six weeks ago.
- For women with therapy-induced amenorrhea, oophorectomy or serial measurements of FSH and/or estradiol are needed to ensure postmenopausal status.
- Patient who does not apply highly effective contraception during the study and through the duration as defined below after the final dose of study treatment:
- Sexually active males (unless surgically sterilized at least 6 months prior to screening) should use a condom during intercourse while taking drug and for 6 months after the final dose of study treatment and should not father a child in this period, but may be recommended to seek advice on conservation of sperm. The use of spermicidal foam is also highly suggested to be used with a condom as another form of protection. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid. Males should be cautioned to not donate sperm while actively receiving treatment on study.
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use highly effective contraception during the study and through 6 months after the final dose of study treatment.
- Herbal preparations/medications are not allowed throughout the study. These herbal medications include, but are not limited to: St. John's wort, Kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, Medical Marijuana and ginseng. Patients need to stop using these herbal medications 7 days prior to first dose of study drug.
- Patient must not eat or drink Seville orange (and juice), grapefruit or grapefruit juice, grapefruit hybrids, pummelos, starfruits and cranberry juice from 7 days prior to the first dose of study drug and during the entire study treatment
- Patient is currently receiving or has received systemic corticosteroids < 2 weeks prior to day 1 of study drug, or who has not fully recovered from side effects of treatment. The following uses of corticosteroids are permitted: single doses, topical applications (e.g., for rash), inhaled sprays (e.g., for obstructive airways diseases), eye drops or local injections (e.g., intra-articular).
- Patient is concurrently using other anti-cancer therapy
Trial locations and contacts
1 site in 1 country.
United States1 site
Rhode Island Hospital and The Miriam Hospital
Providence, Rhode Island, 02903
About this study
Official title: BrUOG 302:BYL719, Capecitabine and Radiation for Rectal Cancer: A Brown University Oncology Research Group Phase I Study
The primary goal of this Brown University Oncology Research Group is to determine that a safe dose of BYL719 can be administered with capecitabine and radiation in patients with rectal cancer. Therefore, the threshold of success for this phase I study is to establish safety.
- Conditions
- Rectal Cancer
- Being tested
- BYL719, Capecitabine, Radiation
- Keywords
- Stage II, Stage III, Stage IV, metastatic
- Medical subject headings
- Rectal Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BYL719Drug
CapecitabineDrug
Also called Xeloda
RadiationRadiation
| Study group | Role | What they receive |
|---|---|---|
| Dose 1 | Experimental | BYL719, capectabine and radiation Dose BYL719: 200mg/day Receives: Drug: BYL719; Drug: Capecitabine; Radiation: Radiation |
| Dose 2 | Experimental | BYL719, capectabine and radiation Dose BYL719: 250mg/day Receives: Drug: BYL719; Drug: Capecitabine; Radiation: Radiation |
| Dose 3 | Experimental | BYL719, capectabine and radiation Dose BYL719: 300mg/day Receives: Drug: BYL719; Drug: Capecitabine; Radiation: Radiation |
| Dose -1 | Experimental | BYL719, capectabine and radiation Dose BYL719: 150mg/day Receives: Drug: BYL719; Drug: Capecitabine; Radiation: Radiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose of BYL719
Measured: approximately 6 weeks
Secondary outcomes (1)
Pathologic Complete Response for Patients With Rectal Cancer
Pathologic complete response is defined as the lack of all signs of cancer in tissue samples removed during surgery or biopsy after treatment with radiation or chemotherapy.
Measured: Approximately 6-10 weeks post treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2015 (estimated)
- Study start3 Jun 2016
- Primary completion16 Nov 2018
- Study completion16 Nov 2018
Why it stopped: lack of accural
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 CancerStudies of the same condition, open and under way.
- 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- This is a phase I dose escalation study adding BYL719 to standard capecitabine and radiation.
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- howard safran
- Sponsor type
- University, hospital or other
- Collaborators
- Brown University, Lifespan, Novartis Pharmaceuticals Corporation (Financial supporter)
- Responsible party
- Sponsor-investigator, howard safran, Brown University
- Investigators
- Howard Safran, MD, Study chair, BrUOG Study Chair
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02550743
- Sponsor's protocol ID
- BrUOG 302
- Status last verified
- Mar 2021
- First submitted
- 11 Sep 2015
- Last updated
- 12 Mar 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 12 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- BrUOG 302:BYL719, Capecitabine and Radiation for Rectal Cancer: A Brown University Oncology Research Group Phase I Study
- ClinicalTrials.gov ID
- NCT02550743
- Acronym / sponsor ID
- BrUOG 302
- Conditions
- Rectal Cancer
- Keywords
- Stage II, Stage III, Stage IV, metastatic
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: lack of accural
- Enrolment
- 7 participants (actual)
- Lead sponsor
- howard safranUniversity, hospital or other
- Collaborators
- Brown University, Lifespan, Novartis Pharmaceuticals Corporation (Financial supporter)
- Study start
- 3 Jun 2016 (actual)
- Primary completion
- 16 Nov 2018 (actual)
- Study completion
- 16 Nov 2018 (actual)
- First posted
- 15 Sep 2015 (estimated)
- Results
- Posted 12 Mar 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary goal of this Brown University Oncology Research Group is to determine that a safe dose of BYL719 can be administered with capecitabine and radiation in patients with rectal cancer. Therefore, the threshold of success for this phase I study is to establish safety.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- This is a phase I dose escalation study adding BYL719 to standard capecitabine and radiation.
| Arm | Type | Receives |
|---|---|---|
| Dose 1 | Experimental | Drug: BYL719, Drug: Capecitabine, Radiation: RadiationBYL719, capectabine and radiation Dose BYL719: 200mg/day |
| Dose 2 | Experimental | Drug: BYL719, Drug: Capecitabine, Radiation: RadiationBYL719, capectabine and radiation Dose BYL719: 250mg/day |
| Dose 3 | Experimental | Drug: BYL719, Drug: Capecitabine, Radiation: RadiationBYL719, capectabine and radiation Dose BYL719: 300mg/day |
| Dose -1 | Experimental | Drug: BYL719, Drug: Capecitabine, Radiation: RadiationBYL719, capectabine and radiation Dose BYL719: 150mg/day |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Patients must have histologically proven adenocarcinoma of the rectum with no evidence of distant metastases.
- The tumor must be clinically Stage II (T3-4 N0) or stage III (N+). Stage of the tumor may be determined by CT scan, endorectal ultrasound or MRI. (For patients receiving chemotherapy prior to protocol chemoradiation, the initial clinical stage applies. CT/MRI/PET should be performed within 2 months of study entry to exclude disease progression.). For the MTD expansion phase only: patients who are stage IV, and in whom it is planned to administer capecitabine and radiation then have a resection of their rectal cancer, are also eligible.
- Measurable disease not required at baseline. Patient's without measurable disease may be enrolled as long as they clinically meet stage II or III criteria or for MTD expansion phase: also stage IV.
- Patients must not have received pelvic radiation for rectal cancer, or prior pelvic radiation for any other malignancy that would prevent the patient from receiving the required radiation treatments for this study. (Patients may receive neoadjuvant chemotherapy prior to study chemoradiation)
- Patients must not have an active concurrent invasive malignancy. Patients with prior malignancies, including invasive colon cancer, are eligible if they are deemed by their physician to be at low risk for recurrence. For example, patients with squamous or basal cell carcinoma of the skin, melanoma in situ, carcinoma of the cervix, or carcinoma in situ of the colon or rectum that have been effectively treated are eligible, even if these conditions were diagnosed within 3 years prior to registration.
Key exclusion criteria (26 listed)
- Patient has a known hypersensitivity to any of the excipients of BYL719 (alpelisib)
- Suspected or confirmed metastatic disease including CNS involvement. For stage IV patients: CNS involvement.
- Patient with clinically manifest diabetes mellitus, or documented steroid induced diabetes mellitus
- Patient with impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral BYL719 (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection). Patients with colostomies are allowed unless colostomy is for one of the precluded reason above.
- Patient who has not recovered to grade 1 or better (except alopecia) from related side effects of any prior antineoplastic therapy
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 |
|---|---|---|
| BYL719 | Drug | Dose -1, Dose 1, Dose 2, Dose 3 |
| CapecitabineAlso: Xeloda | Drug | Dose -1, Dose 1, Dose 2, Dose 3 |
| Radiation | Radiation | Dose -1, Dose 1, Dose 2, Dose 3 |
Primary outcome
Maximum Tolerated Dose of BYL719
Time frame: approximately 6 weeks
1 secondary outcome
Pathologic Complete Response for Patients With Rectal Cancer
Time frame: Approximately 6-10 weeks post treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 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.
Howard Safran, MD study chair
BrUOG Study Chair
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BYL719, Capecitabine and Radiation in people with Rectal Cancer, run by howard safran 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 13 inclusion and 26 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 12 Mar 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 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.
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 12 Mar 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?
Maximum Tolerated Dose of BYL719 (time frame: approximately 6 weeks). 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 12 Mar 2021.