Clinical trial NCT05806931: Sequential TAS-OX Alternating With TAS-IRI Plus Bevacizumab for Late-Line Metastatic Colorectal Cancer
Official title: Sequential Combined TAS-102 and Oxaliplatin Alternating With TAS-102 and Irinotecan (Sequential TASOXIRI) With Bevacizumab for Late-Line Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Colon Cancer
Rectal Cancer
Keywords: Sequential Combined TAS-102
Oxaliplatin
Irinotecan
Late-Line Metastatic Colorectal Cancer
Bevacizumab
Lead sponsor: Rutgers, The State University of New Jersey
Sponsor class: OTHER
First posted: 2023-04-10
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is to evaluate the disease control rate and time to progression of the sequential combination of oxaliplatin with an alternative anti-metabolite Trifluridine/tipiracil hydrochloride mixture, TAS-102,(TAS-OX) as well as irinotecan in combination with TAS-102 oxaliplatin(TAS-OX) + Bevacizumab in late-line metastatic colorectal cancer (mCRC)

Detailed description: This phase II trial will evaluate efficacy of TAS-OX alternating with TAS-IRI (sequential TASOXIRI) with Bevacizumab, in the treatment of mCRC. Participants will be treated with the study drugs until radiological evidence of disease progression or until treatment discontinuation secondary to adverse events.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed stage IV colon cancer (AJCC 7th edition) that has progressed after standard therapy that included 5-FU, irinotecan, oxaliplatin and appropriate antibody therapy. Antibody therapy with bevacizumab and an anti-EGFR antibody, if RAS wild type, should have been given unless medical reasons have precluded their use. Participants who could not tolerate standard agents because of unacceptable, but reversible toxicity necessitating their discontinuation will be allowed to participate.
* Participants who had received adjuvant chemotherapy and had recurrence during or within six months of completion of the adjuvant chemotherapy will be allowed to count the adjuvant therapy as one chemotherapy regimen for advanced disease.
* Progression of disease must be documented on the most recent scan.
* Presence of measurable disease
* RAS mutation and MMR status must be determined (or tissue availability for testing if not already determined).
* Age 18 years or older.
* ECOG performance status 0-1.
* Life expectancy of at least three months.
* Participants with adequate organ function:

  1. Absolute neutrophil count (ANC) \> 1.5 x 109/L
  2. Hemoglobin \> 9 g/dL
  3. Platelets (PLT) \> 70 x 109/L
  4. AST/ALT \< 5 x ULN
  5. Albumin within normal limits for institution
* Women who are nursing and discontinue nursing prior to enrollment in the program.
* Ability to take oral medication (i.e., no feeding tube).
* Participant able and willing to comply with study procedures as per protocol.
* Participant able to understand and willing to sign and date the written voluntary informed consent form (ICF) at screening visit prior to any protocol-specific procedures.

Exclusion Criteria:

* Participants who have previously received TAS-102.
* Grade 3 or higher peripheral neuropathy (functional impairment).
* Inability to tolerate irinotecan previously (due to uncontrolled diarrhea)
* There are no specific exclusions for bevacizumab. Bevacizumab should be given unless there are specific contraindications per the treating investigator, which should be stated. If UPC is \>1.0 (as above) hold bevacizumab until proteinuria resolves and then start bevacizumab.
* Symptomatic CNS metastases requiring treatment.
* Other active malignancy within the last three years (except for non-melanoma skin cancer or a non-invasive/in situ cancer).
* Pregnancy or breast feeding.
* Current therapy with other investigational agents.
* Active infection with body temperature \> 38°C due to infection.
* Major surgery within prior four weeks (the surgical incision should be fully healed prior to drug administration).
* Any anticancer therapy within prior two weeks of first dose of study drug.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to TAS-102.
* Current therapy with other investigational agents or participation in another clinical study or any investigational agent received within prior four weeks.
* Grade 3 or higher hypersensitivity reaction to oxaliplatin or irinotecan, or grade 1-2 hypersensitivity reaction to oxaliplatin not controlled with pre-medication.
* Has unresolved toxicity of greater than or equal to Common Terminology Criteria for Adverse (CTCAE) Grade 2 attributed to any prior therapies (excluding anemia, alopecia, skin pigmentation, and platinum-induced neurotoxicity).

Primary outcomes:
measure: Disease control rate (DCR):
timeFrame: From baseline until the date of first documented progression of disease, as assessed up to 100 months
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, on average up to 100 months
measure: Overall Survival (OS)
timeFrame: From date of randomization until the date of death up to 100 months
measure: Overall Response Rate (ORR)
timeFrame: From the date of randomization and measured through the course of study treatment, assessed up to 100 months
measure: Duration of Response
timeFrame: From the date of response until the date of first documented disease progression or death, assessed up to 100 months
Other outcomes:
Locations:
city: Elizabeth
country: United States
facility: Trinitas Hospital and Comprehensive Cancer Center
state: New Jersey
city: Jersey City
country: United States
facility: RWJBarnabas Health Jersey City Medical Center
state: New Jersey
city: Lakewood
country: United States
facility: RWJBarnabas Health - Monmouth Medical Center Southern Campus
state: New Jersey
city: Livingston
country: United States
facility: Cooperman Barnabas Medical Center (Saint Barnabas Medical Center)
state: New Jersey
city: Long Branch
country: United States
facility: RWJBarnabas Health - Monmouth Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: New Brunswick
country: United States
facility: RWJBarnabas Health - Robert Wood Johnson University Hospital
state: New Jersey
city: Somerset
country: United States
facility: RWJBarnabas Health - Robert Wood Johnson University Hospital
state: New Jersey
city: Toms River
country: United States
facility: RWJBarnabas Health - Community Medical Center
state: New Jersey
Study officials:
affiliation: Cancer Institute of New Jersey Rutgers
name: Howard S. Hochster, MD
role: PRINCIPAL_INVESTIGATOR
References: