Capecitabine Plus Concomitant Radiation Therapy Followed by Durvalumab as Preoperative Treatment in Rectal Cancer

NCT04083365 | Unknown Phase 2

• 1 other identifier: PANDORA
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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. 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

Outcome Measures

Primary Outcomes (1)

• 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.

  36 months

Secondary Outcomes (2)

• The clinical complete remission rate (cCR) after durvalumab treatment

  36 months

• Disease-free survival (DSF)

  60 months

Study Arms (1)

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

Drug: Capecitabine; Drug: Radiotherapy; Drug: Durvalumab

Interventions

Capecitabine DRUG

chemoradiation therapy with 825 mg/m2 twice daily capecitabine every day for 5 weeks

CAPECITABINE + concomitant RT + Durvalumab

Radiotherapy DRUG

5040 cGy radiotherapy for 5 days per week for 5 weeks

CAPECITABINE + concomitant RT + Durvalumab

Durvalumab DRUG

One week after the end of CT/RT patients will be treated with 1500 mg IV Q4W durvalumab for 3 administrations

CAPECITABINE + concomitant RT + Durvalumab

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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).

You may not qualify if:

• 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
• 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:

Sponsors & Collaborators

• AUSL Romagna Rimini: lead
• AstraZeneca: collaborator
• Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS: collaborator

Study Sites (1)

Ospedale Degli Infermi Uo Oncologia

Faenza, 48018, Italy

RECRUITING

Related Publications (1)

• 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.

  PMID: 37774508 DERIVED

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Capecitabine; Radiotherapy; durvalumab

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Therapeutics

Central Study Contacts

STEFANO TAMBERI

CONTACT

0546601193; stefano.tamberi@auslromagna.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2019
• First Posted: September 10, 2019
• Study Start: January 1, 2020
• Primary Completion: November 30, 2022
• Study Completion: August 31, 2025
• Last Updated: May 31, 2023

Record last verified: 2023-05

Locations

IT (1)