CAPEcitabine eXtension of Adjuvant Therapy for Pancreatic Adenocarcinoma: (CAPE-X)

NCT06110598 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: CASE3223
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

• This study is being done to find out if extending adjuvant chemotherapy for patients by giving additional chemotherapy can lengthen the amount of time before their cancer comes back. The additional chemotherapy is called capecitabine.
• Capecitabine is an oral drug (taken by mouth). It is approved by the US Food and Drug Administration (FDA) for adjuvant treatment of adults with pancreatic cancer and also for the treatment of other types of cancer

Conditions

Pancreas Cancer; Pancreas Adenocarcinoma

Keywords

pancreas

Outcome Measures

Primary Outcomes (1)

• Relapse-free survival (RFS)

  Relapse-free survival (RFS), defined as the time from randomization to first documentation of disease relapse or death, defined as radiographic evidence of local or distant primary tumor relapse, whichever occurs first; participants alive without relapse will be censored at the date of last disease assessment.

  Assessed every 3 months from the date of randomization until the first documentation of disease relapse or death, up to 24 months, and then every 6 months after the initial 24 months up to 4 years

Secondary Outcomes (1)

• Overall survival (OS)

  Assessed every 3 months from the date of randomization until the first documentation of disease relapse or death, up to 24 months, and then every 6 months after the initial 24 months up to 4 years

Study Arms (2)

Arm A: Extended adjuvant therapy with capecitabine

EXPERIMENTAL

* Participants randomized to Arm A will take capecitabine (1000mg by mouth twice a day, 3-week cycle \[2 weeks on therapy, 1 week off\]) for up to 18 cycles, or until progression or intolerance to therapy develops. * Participants who remain without disease recurrence at completion of 18 cycles of therapy who wish to continue therapy may do so at the discretion of their treating medical oncologist. Participants will be followed at standard 12-week intervals, where they will undergo routine cross-sectional imaging and labs.

Drug: Capecitabine

Arm B: Active surveillance

NO INTERVENTION

* Participants randomized to Arm B will undergo active surveillance, with no active treatment for the duration of their participation in the study. * Participants in Arm B will undergo re-staging every 12 weeks (+/- 7 days), consisting of cross-sectional imaging (CT or PET-CT) and labs (CBC, chemistry panel, CA19-9 and blood draw for ctDNA). In addition to re-staging every 12 weeks, participants may be seen by their medical or surgical oncologist as clinically indicated. Participants who experience disease relapse may transition to palliative systemic therapy or best supportive care at the discretion of their treating medical oncologist.

Interventions

Capecitabine DRUG

Capecitabine is an oral prodrug that is enzymatically converted to 5-fluorouracil (5-FU) in vivo. Both normal and tumor cells metabolize 5-FU to 5-fluoro-2'-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP). These metabolites cause cell injury by two different mechanisms. First, FdUMP and the folate cofactor, N5-10-methylenetetrahydrofolate, bind to thymidylate synthase (TS) to form a covalently bound ternary complex. This binding inhibits the formation of thymidylate from 2'-deoxyuridylate. Thymidylate is the necessary precursor of thymidine triphosphate, which is essential for the synthesis of DNA, so that a deficiency of this compound can inhibit cell division. Second, nuclear transcriptional enzymes can mistakenly incorporate FUTP in place of uridine triphosphate (UTP) during the synthesis of RNA. This metabolic error can interfere with RNA processing and protein synthesis.

Also known as: Xeloda®

Arm A: Extended adjuvant therapy with capecitabine

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have histologically or cytologically confirmed pancreatic adenocarcinoma.
• Participants must have undergone curative-intent surgical resection and received at least 4 months of multi-agent cytotoxic chemotherapy, regardless of treatment sequence or chemotherapy backbone.
• Participants must be within 12 weeks of completion of standard perioperative therapy (defined as resection, multi-agent systemic chemotherapy, + radiotherapy, regardless of treatment sequence).
• Participants must have absence of or unknown BRCA1, BRCA2, or PALB2 germline or somatic mutational status.
• Participants must have no evidence of recurrent disease.
• Age \>18 years because no high-quality dosing or adverse event data are currently available on the use of capecitabine in in participants ≤18 years of age. Additionally, pancreatic adenocarcinoma is exceedingly rare in participants \<18 years of age. Therefore, children are excluded from this study.
• ECOG(Eastern Cooperative Oncology Group) Performance status \< 2.
• Participants must have normal organ and marrow function as defined below:
• Hemoglobin ≥ 10.0 g/dl
• Leukocytes ≥ 3,000/mcL
• Absolute neutrophil count ≥ 1,500/mcL
• Platelet count ≥ 100,000/mcL
• Total bilirubin within normal institutional limits
• AST(Aspartate aminotransferase) (SGOT) ≤ 2.5 X institutional upper limit of normal
• ALT (SGPT) ≤ 2.5 X institutional upper limit of normal

You may not qualify if:

• Prior treatment toxicities resolved to ≤ Grade 3 according to NCI CTCAE Version 5.0 (list exceptions, e.g. alopecia, neuropathy, fatigue, etc).
• Participants receiving any other investigational agents or participating in clinical trials that use OS or PFS(progression-free survival) as their primary or secondary endpoints would prohibit participation in the current study. Patients enrolled or previously enrolled in non-therapeutic trials, or trials with only correlative endpoints are allowed.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to capecitabine or 5-fluorouracil.
• Participants with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Participants with known low or absent dihydropyimidine dehydrogenase (DPD)activity
• Women who are pregnant or breastfeeding are excluded from this study because capecitabine is a category D agent with the potential for teratogenic or abortifacient effects. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with capecitabine, breastfeeding should be discontinued if the mother is treated with capecitabine.
• Participants who are known to be HIV-positive on combination antiviral therapy are ineligible because of the potential for pharmacokinetic interaction with capecitabine. In addition, these participants are at increased risk of lethal infections when treated with marrow suppressive therapy.

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead

Study Sites (1)

University Hospitals Cleveland Medical Center, Seidman Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106-5065, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Capecitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System 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

Study Officials

• Lee M Ocuin, MD, FACS

  Case Comprehensive Cancer Center, University Hospitals, Cleveland Medical Center, Seidman Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be randomized 2:1 to the treatment arm. There will be no blinding of participants and the trial will not be placebo-controlled

Study Record Dates

• First Submitted: October 19, 2023
• First Posted: October 31, 2023
• Study Start: December 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: August 15, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Starting 9 months and ending 36 months following article publication

Locations

US (1)