RECTAL CANCERPhase 2PANDORANCT04083365
Capecitabine Plus Concomitant Radiation Therapy Followed by Durvalumab as Preoperative Treatment in Rectal Cancer
A Phase 2 study testing Capecitabine, Radiotherapy and Durvalumab in people with RECTAL CANCER, run by AUSL Romagna Rimini at 1 site in Italy.
Trial summary
This is a prospective phase II, open label, single arm, multi-centre study to evaluate activity of an innovative sequence on capecitabine plus concomitant radiation therapy followed by durvalumab in patients with operable rectal cancer. The enrollment period will be of 12 months. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- RECTAL CANCER
- What is being tested?
- Capecitabine, Radiotherapy and Durvalumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteItaly
- Study dates
- 1 Jan 2020to 31 Aug 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and Data Privacy Directive obtained from the patient/legal representative prior to performing any protocol- related procedures, including screening evaluations.
- Age > 18 years at time of study entry.
- Eastern Cooperative Oncology Group (ECOG) 0 or 1.
- Histological diagnosis of adenocarcinoma of rectum.
- Clinical stage 2-3 rectal adenocarcinoma, cT3/4N0/M0 or Tx N1-2/M0, assessed by thorax abdomen pelvis with contrast Computed tomography (CT) scan, pelvi Magnetic resonance imaging (MRI) scan, pancolonscopy.
- Able to swallow oral medication.
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- Body weight >30kg.
- Adequate normal organ and marrow function as defined below:
- Haemoglobin ≥9.0 g/dL - Absolute neutrophil count (ANC) > 1500 per mm3
- Platelet count >100.000 per mm3
- Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of haemolysis or hepatic pathology), who will be allowed only in consultation with their physician.
- AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal
- Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976).
- Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre- menopausal patients. Women of childbaring potential or male patients with a female partner of childbearing potential must agree to use at least 1 highly effective method of contraception from the time of screening throughout the total duration of the drug treatment and the drug washout period (90 days after the last dose of durvalumab monotherapy) as detailed in section 7.1. Women will be considered post-menopausal if they have been amenorrhoeic for 12 months without an alternative medical cause. The following age-specific requirements apply:
- Women <50 years of age would be considered post-menopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post- menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
- Women ≥50 years of age would be considered post-menopausal if they have been amenorrhoeic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
- Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up. 11. Must have a life expectancy of at least 12 weeks.
Who cannot join
- Previous treatment for local advanced rectum cancer.
- Concurrent enrolment in another clinical study unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study. 3. Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab.
- History of hypersensitivity to fluorouracil.
- Known Dihydropyrimidine dehydrogenase (DPD) deficiency.
- History of another primary malignancy except for:
- Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of study drug and of low potential risk for recurrence
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- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease - Adequately treated carcinoma in situ without evidence of disease e.g., cervical cancer in situ
- Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. The following are exceptions to this criterion:
- Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
- Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
- Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
- Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
- Major surgical procedure within 28 days prior to the first dose of treatment.
- History of allogenic organ transplantation.
- Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
- Patients with vitiligo or alopecia
- Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement - Any chronic skin condition that does not require systemic therapy
- Patients without active disease in the last 5 years may be included but only after consultation with the study physician
- Patients with celiac disease controlled by diet alone
- Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
- History of leptomeningeal carcinomatosis.
- History of active primary immunodeficiency.
- Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
- Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP.
- Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ highly effective birth control from screening to 90 days after the last dose of durvalumab monotherapy.
- Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
- Judgment by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements.
- Patients unable to follow the Protocol procedures and to sign the informed consent. In the case of patients' incapable of giving informed consent, it must be provided and signed by guardians or legal representative. Patients incapable must also sign the agreement to the extent that they are able to do so.
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Ospedale Degli Infermi Uo Oncologia
Faenza, 48018
STEFANO TAMBERI
stefano.tamberi@auslromagna.it
About this study
Official title: A Phase II Study of Capecitabine Plus Concomitant Radiotion Therapy Followed by Durvalumab (MEDI4736) as Preoperative Treatment in Rectal Cancer.
This is a prospective phase II, open label, single arm, multi-centre study to evaluate activity of an innovative sequence on capecitabine plus concomitant radiation therapy followed by durvalumab in patients with operable rectal cancer. The enrollment period will be of 12 months. Eligible patients will be initiated to a standard concomitant chemoradiation therapy for 5 weeks. One week after the end of CT/RT patients will be treated with durvalumab for 3 administrations. Patient will undergo surgery after 10-12 weeks from the end of CT/RT and the surgical piece will be analyzed. After surgery patients will be followed up for 5 years, according to clinical practice.
- Conditions
- RECTAL CANCER
- Being tested
- Capecitabine, Radiotherapy, Durvalumab
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CapecitabineDrug
chemoradiation therapy with 825 mg/m2 twice daily capecitabine every day for 5 weeks
RadiotherapyDrug
5040 cGy radiotherapy for 5 days per week for 5 weeks
DurvalumabDrug
One week after the end of CT/RT patients will be treated with 1500 mg IV Q4W durvalumab for 3 administrations
| Study group | Role | What they receive |
|---|---|---|
| CAPECITABINE + concomitant RT + Durvalumab | Experimental | After careful staging, patients will be initiated to a standard concomitant chemoradiation therapy with 825 mg/m2 twice daily capecitabine every day for 5 weeks and 5040 cGy radiotherapy for 5 days per week for 5 weeks. At the end of treatment patients will undergo a lesion biopsy. One week after the end of CT/RT patients will be treated with 1500 mg IV Q4W durvalumab for 3 administrations. From week 9 to 10 after neoadjuvant therapy will be performed re-staging with CT and MRI scan. Surgery will be performed at week 10-12 from the end of CT/RT and the surgical piece will be analyzed Receives: Drug: Capecitabine; Drug: Radiotherapy; Drug: Durvalumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathological complete response (pCR) rate after durvalumab treatment
The primary end point will be assessed by means of the proportion of patients having complete pathological response pCR after durvalumab treatment. Corresponding two-sided 95% confidence intervals (CIs) will be computed.
Measured: 36 months
Secondary outcomes (2)
The clinical complete remission rate (cCR) after durvalumab treatment
The secondary endpoints are the clinical complete remission rate (cCR) after durvalumab treatment, before surgery. The secondary end point will be assessed by means of the proportion of patients having complete remission rate (cCR) after durvalumab treatment. Corresponding two-sided 95% confidence intervals (CIs) will be computed.
Measured: 36 months
Disease-free survival (DSF)
The disease-free survival will be evaluated during a follow up of 5 years. . DFS will be estimated by using Kaplan-Meier approach
Measured: 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2019
- Study start1 Jan 2020
- Primary completion30 Nov 2022
- Study completion31 Aug 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AUSL Romagna Rimini
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca, Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04083365
- Sponsor's protocol ID
- PANDORA
- Acronym
- PANDORA
- Status last verified
- May 2023
- First submitted
- 30 Aug 2019
- Last updated
- 31 May 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Grassi E, Zingaretti C, Petracci E, Corbelli J, Papiani G, Banchelli I, Valli I, Frassineti GL, Passardi A, Di Bartolomeo M, Pietrantonio F, Gelsomino F, Carandina I, Banzi M, Martella L, Bonetti AV, Boccaccino A, Molinari C, Marisi G, Ugolini G, Nanni O, Tamberi S. Phase II study of capecitabine-based concomitant chemoradiation followed by durvalumab as a neoadjuvant strategy in locally advanced rectal cancer: the PANDORA trial. ESMO Open. 2023 Oct;8(5):101824. doi: 10.1016/j.esmoop.2023.101824. Epub 2023 Sep 27.
PubMed 37774508
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Capecitabine Plus Concomitant Radiotion Therapy Followed by Durvalumab (MEDI4736) as Preoperative Treatment in Rectal Cancer.
- ClinicalTrials.gov ID
- NCT04083365
- Acronym / sponsor ID
- PANDORA / PANDORA
- Conditions
- RECTAL CANCER
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- AUSL Romagna RiminiUniversity, hospital or other
- Collaborators
- AstraZeneca, Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS
- Study start
- 1 Jan 2020 (actual)
- Primary completion
- 30 Nov 2022 (actual)
- Study completion
- 31 Aug 2025 (estimated)
- First posted
- 10 Sep 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a prospective phase II, open label, single arm, multi-centre study to evaluate activity of an innovative sequence on capecitabine plus concomitant radiation therapy followed by durvalumab in patients with operable rectal cancer. The enrollment period will be of 12 months. Eligible patients will be initiated to a standard concomitant chemoradiation therapy for 5 weeks. One week after the end of CT/RT patients will be treated with durvalumab for 3 administrations. Patient will undergo surgery after 10-12 weeks from the end of CT/RT and the surgical piece will be analyzed. After surgery patients will be followed up for 5 years, according to clinical practice.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CAPECITABINE + concomitant RT + Durvalumab | Experimental | Drug: Capecitabine, Drug: Radiotherapy, Drug: DurvalumabAfter careful staging, patients will be initiated to a standard concomitant chemoradiation therapy with 825 mg/m2 twice daily capecitabine every day for 5 weeks and 5040 cGy radiotherapy for 5 days per week for 5 weeks. At the end of treatment patients will undergo a lesion biopsy. One week after the end of CT/RT patients will be treated with 1500 mg IV Q4W durvalumab for 3 administrations. From week 9 to 10 after neoadjuvant therapy will be performed re-staging with CT and MRI scan. Surgery will be performed at week 10-12 from the end of CT/RT and the surgical piece will be analyzed |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and Data Privacy Directive obtained from the patient/legal representative prior to performing any protocol- related procedures, including screening evaluations.
- Age > 18 years at time of study entry.
- Eastern Cooperative Oncology Group (ECOG) 0 or 1.
- Histological diagnosis of adenocarcinoma of rectum.
- Clinical stage 2-3 rectal adenocarcinoma, cT3/4N0/M0 or Tx N1-2/M0, assessed by thorax abdomen pelvis with contrast Computed tomography (CT) scan, pelvi Magnetic resonance imaging (MRI) scan, pancolonscopy.
Key exclusion criteria (28 listed)
- Previous treatment for local advanced rectum cancer.
- Concurrent enrolment in another clinical study unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study. 3. Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab.
- History of hypersensitivity to fluorouracil.
- Known Dihydropyrimidine dehydrogenase (DPD) deficiency.
- History of another primary malignancy except for:
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 |
|---|---|---|
| Capecitabinechemoradiation therapy with 825 mg/m2 twice daily capecitabine every day for 5 weeks | Drug | CAPECITABINE + concomitant RT + Durvalumab |
| Radiotherapy5040 cGy radiotherapy for 5 days per week for 5 weeks | Drug | CAPECITABINE + concomitant RT + Durvalumab |
| DurvalumabOne week after the end of CT/RT patients will be treated with 1500 mg IV Q4W durvalumab for 3 administrations | Drug | CAPECITABINE + concomitant RT + Durvalumab |
Primary outcome
Pathological complete response (pCR) rate after durvalumab treatment
Time frame: 36 months
The primary end point will be assessed by means of the proportion of patients having complete pathological response pCR after durvalumab treatment. Corresponding two-sided 95% confidence intervals (CIs) will be computed.
2 secondary outcomes
The clinical complete remission rate (cCR) after durvalumab treatment
Time frame: 36 months
Disease-free survival (DSF)
Time frame: 60 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 May 2023.
- Derived from this study: PubMed 37774508Grassi E, Zingaretti C, Petracci E, Corbelli J, Papiani G, Banchelli I, Valli I, Frassineti GL, Passardi A, Di Bartolomeo M, Pietrantonio F, Gelsomino F, Carandina I, Banzi M, Martella L, Bonetti AV, Boccaccino A, Molinari C, Marisi G, Ugolini G, Nanni O, Tamberi S. Phase II study of capecitabine-based concomitant chemoradiation followed by durvalumab as a neoadjuvant strategy in locally advanced rectal cancer: the PANDORA trial. ESMO Open. 2023 Oct;8(5):101824. doi: 10.1016/j.esmoop.2023.101824. Epub 2023 Sep 27.
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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.
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 Capecitabine, Radiotherapy and Durvalumab in people with RECTAL CANCER, run by AUSL Romagna Rimini at 1 site in Italy.
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 17 inclusion and 28 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: status not confirmed, as of the sponsor's last update on 31 May 2023. 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 Italy. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact STEFANO TAMBERI (0546601193, stefano.tamberi@auslromagna.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathological complete response (pCR) rate after durvalumab treatment (time frame: 36 months). 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 NCT04083365, which also lists 1 linked publication.
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 31 May 2023.