Colorectal NeoplasmsPhase 1/2NCT02848079
TAS-OX for Refractory Metastatic Colon Cancer
A Phase 1/2 study testing combined TAS-102 and TAS-OX in people with Colorectal Neoplasms, run by Yale University at 1 site in United States.
Trial summary
This study will examine the safety and effectiveness of oxaliplatin in combination with TAS-102 (TAS-OX) for treatment of patients with metastatic colorectal cancer whose cancer has progressed or recurred after FOLFOX chemotherapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Neoplasms
- What is being tested?
- combined TAS-102 and TAS-OX
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Oct 2016to 2 Jun 2020
- Phase
- Phase 1/2
- 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
- Histologically confirmed stage IV colon cancer (AJCC 7th edition) that has progressed after standard therapy that included 5-FU, irinotecan and oxaliplatin. Patients who could not tolerate standard agents because of unacceptable, but reversible, toxicity necessitating their discontinuation will be allowed to participate.
- Patients who had received adjuvant chemotherapy and had recurrence during or within 6 months of completion of the adjuvant chemotherapy will be allowed to count the adjuvant therapy as one chemotherapy regimen.
- Progression of disease must be documented on the most recent scan.
- Presence of measurable disease (not required for Phase 1 portion of the trial).
- Retrovirus-associated DNA sequences (RAS) mutation and mismatch repair (MMR) status must be determined (or tissue availability for testing if not already determined)
- Age 18 years or older.
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- Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
- Life expectancy of at least 3 months.
- Patient with adequate organ function:
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- Hemoglobin ≥ 9 g/dL
- Platelets (PLT) ≥ 75 x 109/L
- Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT) ≤ 5 x Upper limit of normal (ULN)
- Total serum bilirubin of ≤1.5 mg/dL (except for Grade 1 hyperbilirubinemia due solely to a medical diagnosis of Gilbert's syndrome).
- Albumin ≥ 2.5 g/dL
- Serum creatinine ≤ 1.5 x institutional ULN (Cockcroft and Gault formula)
- Adequate contraception if applicable.
- Women who are nursing must discontinue nursing prior to enrollment in the program.
- Ability to take oral medication (i.e. no feeding tube).
- Patient able and willing to comply with study procedures as per protocol.
- Patient 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.
Who cannot join
- Patients who have previously received TAS-102.
- Grade 2 or higher peripheral neuropathy.
- Symptomatic Central nervous system (CNS) metastases requiring treatment.
- Other active malignancy within the last 3 years (except for non-melanoma skin cancer or a non-invasive/in situ cancer).
- Pregnancy or breast feeding.
- Current therapy with other investigational agents.
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- Active infection with body temperature ≥38°C due to infection.
- Major surgery within prior 4 weeks (the surgical incision should be fully healed prior to drug administration).
- Any anticancer therapy within prior 3 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 4 weeks.
- Grade 3 or higher hypersensitivity reaction to oxaliplatin, or grade 1-2 hypersensitivity reaction to oxaliplatin not controlled with pre-medication.
- Unresolved toxicity of greater than or equal to Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 attributed to any prior therapies (excluding anemia, alopecia, skin pigmentation, and platinum-induced neurotoxicity).
- Extended field radiation within prior 4 weeks of first dose of study drug or limited field radiation within prior 2 weeks of first dose of study drug.
- Psychological, familial, or sociological condition potentially hampering compliance with the study protocol and follow-up schedule.
- Involvement in the planning and/or conduct of the study.
- Previous enrollment in the present study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: TAS-102 and Oxaliplatin (TAS-OX) for Refractory Metastatic Colon Cancer
This study will examine the safety and effectiveness of oxaliplatin in combination with TAS-102 (TAS-OX) for treatment of patients with metastatic colorectal cancer whose cancer has progressed or recurred after FOLFOX chemotherapy.
Read the detailed description
TAS-102 is an oral agent, which consists of a combination of a novel antimetabolite 5-trifluorothymidine (FTD) and a thymidine phosphorylase inhibitor (TPI) that prevents degradation of FTD. It has demonstrated activity in chemorefractory metastatic colorectal cancer (mCRC) patients. In the Japanese randomized phase II trial, TAS-102 improved medial overall survival when compared to placebo (9.0 vs.6.6 months, Hazard Ratio (HR) 0.56) in patients with mCRC refractory to 5-fluorouracil (5-FU), irinotecan and oxaliplatin. Subsequently, a randomized phase III study conducted in 13 countries (RECOURSE trial) confirmed this benefit on overall survival when compared to placebo (7.1 months vs. 5.3 months, HR 0.68) in patients with refractory metastatic colorectal cancer (CRC) 5.
Oxaliplatin is a third generation platinum compound, which is active when used together with 5-FU in the treatment of mCRC (FOLFOX). FOLFOX chemotherapy, which is frequently combined with anti-angiogenic agent Bevacizumab, is widely accepted as the preferred first-line regimen in the treatment of this disease in the US. Oxaliplatin is also frequently reintroduced in more advanced settings. Reintroduction is seen after progression on maintenance therapy, after resolution of previous treatment limiting neuropathy, after disease recurrence post adjuvant treatment or post metastasectomy. In the control arm of a randomized study of FOLFOX4 or FOLFOX7 with oxaliplatin in a stop-and-go fashion in advanced colorectal cancer (OPTIMOX1 study), oxaliplatin was reintroduced in 27% of patients. Although patients derive clinical benefit when oxaliplatin is reintroduced, the response rates are not as robust as during initial exposures. Decreased efficacy may be at least in part due to prolonged exposure and resultant resistance to 5-FU, which is a backbone in maintenance and in oxaliplatin containing regimens. Hence, the investigators propose exploring the safety and efficacy of oxaliplatin in combination with an alternative anti-metabolite TAS-102 (TAS-OX).
TAS-102 has demonstrated activity in 5-FU refractory mCRC, so the investigators hypothesize that TAS-OX may serve as an alternative drug combination for patients who have progressed or recurred after FOLFOX, and who are candidates for additional oxaliplatin therapy.
This is a 2-part clinical trial with TAS-102 in combination with oxaliplatin. The first part will be a dose-finding run-in phase and will enroll 3-18 patients. The second part, the focus of this study, will be a single arm cohort , which will further evaluate the safety, as well as efficacy, of TAS-OX in the treatment of mCRC. The subjects in part 2 will be treated with the drug doses determined in Part 1 of the trial. Up to 50 patients will be enrolled in part 2. Anticipated enrollment may be as high as 68 patients. Maximum potential enrollment is listed under anticipated enrollment, below.
- Conditions
- Colorectal Neoplasms
- Being tested
- combined TAS-102 and TAS-OX
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
combined TAS-102 and TAS-OXDrug
Combination treatment with TAS-102 and oxaliplatin. TAS-102 is an oral medication; oxaliplatin (TAS-OX) is given by infusion.
| Study group | Role | What they receive |
|---|---|---|
| combined TAS-102 and oxaliplatin | Experimental | Combination treatment with TAS-102 and oxaliplatin. Combination treatment with TAS-102 and oxaliplatin. TAS-102 is an oral medication; oxaliplatin (TAS-OX) is given by infusion. In Part 1 treatments were started at level 1 doses, which were based on prior clinical experience with the medications studied. Dose escalation followed a traditional "3+3" design. The subjects in Part 2 were treated with dose level 3.
Oxaliplatin infusion was given on day 1 of each cycle. TAS-102 was taken twice daily on days 1-5 of each cycle. Receives: Drug: combined TAS-102 and TAS-OX |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate
Overall Response Rate was measured by Response Evaluation Criteria In Solid Tumor (RECIST) 1.1 criteria. Tumors were assessed with CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.".
Measured: up to 30 days following discontinuation of treatment
Secondary outcomes (2)
Progression Free Survival
Progression Free Survival was assessed according to RECIST criteria version 1.1. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Measured: from the date of start of treatment to the date of first documented progression or any cause of death assessed up to 12 months.
Overall Survival
Overall Survival was assessed by the time to death from start of study.
Measured: from the date of start of treatment to the date of any cause of death assessed up to 24 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2016 (estimated)
- Study start31 Oct 2016
- Primary completion2 Jun 2020
- Study completion2 Jun 2020
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 Colorectal NeoplasmsStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jeremy S. Kortansky, M.D., Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02848079
- Sponsor's protocol ID
- 1605017852
- Status last verified
- Jun 2021
- First submitted
- 21 Jul 2016
- Last updated
- 20 Jul 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 20 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- TAS-102 and Oxaliplatin (TAS-OX) for Refractory Metastatic Colon Cancer
- ClinicalTrials.gov ID
- NCT02848079
- Acronym / sponsor ID
- 1605017852
- Conditions
- Colorectal Neoplasms
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Study start
- 31 Oct 2016 (actual)
- Primary completion
- 2 Jun 2020 (actual)
- Study completion
- 2 Jun 2020 (actual)
- First posted
- 28 Jul 2016 (estimated)
- Results
- Posted 20 Jul 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will examine the safety and effectiveness of oxaliplatin in combination with TAS-102 (TAS-OX) for treatment of patients with metastatic colorectal cancer whose cancer has progressed or recurred after FOLFOX chemotherapy.
Detailed description
TAS-102 is an oral agent, which consists of a combination of a novel antimetabolite 5-trifluorothymidine (FTD) and a thymidine phosphorylase inhibitor (TPI) that prevents degradation of FTD. It has demonstrated activity in chemorefractory metastatic colorectal cancer (mCRC) patients. In the Japanese randomized phase II trial, TAS-102 improved medial overall survival when compared to placebo (9.0 vs.6.6 months, Hazard Ratio (HR) 0.56) in patients with mCRC refractory to 5-fluorouracil (5-FU), irinotecan and oxaliplatin. Subsequently, a randomized phase III study conducted in 13 countries (RECOURSE trial) confirmed this benefit on overall survival when compared to placebo (7.1 months vs. 5.3 months, HR 0.68) in patients with refractory metastatic colorectal cancer (CRC) 5.
Oxaliplatin is a third generation platinum compound, which is active when used together with 5-FU in the treatment of mCRC (FOLFOX). FOLFOX chemotherapy, which is frequently combined with anti-angiogenic agent Bevacizumab, is widely accepted as the preferred first-line regimen in the treatment of this disease in the US. Oxaliplatin is also frequently reintroduced in more advanced settings. Reintroduction is seen after progression on maintenance therapy, after resolution of previous treatment limiting neuropathy, after disease recurrence post adjuvant treatment or post metastasectomy. In the control arm of a randomized study of FOLFOX4 or FOLFOX7 with oxaliplatin in a stop-and-go fashion in advanced colorectal cancer (OPTIMOX1 study), oxaliplatin was reintroduced in 27% of patients. Although patients derive clinical benefit when oxaliplatin is reintroduced, the response rates are not as robust as during initial exposures. Decreased efficacy may be at least in part due to prolonged exposure and resultant resistance to 5-FU, which is a backbone in maintenance and in oxaliplatin containing regimens. Hence, the investigators propose exploring the safety and efficacy of oxaliplatin in combination with an alternative anti-metabolite TAS-102 (TAS-OX).
TAS-102 has demonstrated activity in 5-FU refractory mCRC, so the investigators hypothesize that TAS-OX may serve as an alternative drug combination for patients who have progressed or recurred after FOLFOX, and who are candidates for additional oxaliplatin therapy.
This is a 2-part clinical trial with TAS-102 in combination with oxaliplatin. The first part will be a dose-finding run-in phase and will enroll 3-18 patients. The second part, the focus of this study, will be a single arm cohort , which will further evaluate the safety, as well as efficacy, of TAS-OX in the treatment of mCRC. The subjects in part 2 will be treated with the drug doses determined in Part 1 of the trial. Up to 50 patients will be enrolled in part 2. Anticipated enrollment may be as high as 68 patients. Maximum potential enrollment is listed under anticipated enrollment, below.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| combined TAS-102 and oxaliplatin | Experimental | Drug: combined TAS-102 and TAS-OXCombination treatment with TAS-102 and oxaliplatin. Combination treatment with TAS-102 and oxaliplatin. TAS-102 is an oral medication; oxaliplatin (TAS-OX) is given by infusion. In Part 1 treatments were started at level 1 doses, which were based on prior clinical experience with the medications studied. Dose escalation followed a traditional "3+3" design. The subjects in Part 2 were treated with dose level 3. Oxaliplatin infusion was given on day 1 of each cycle. TAS-102 was taken twice daily on days 1-5 of each cycle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Histologically confirmed stage IV colon cancer (AJCC 7th edition) that has progressed after standard therapy that included 5-FU, irinotecan and oxaliplatin. Patients who could not tolerate standard agents because of unacceptable, but reversible, toxicity necessitating their discontinuation will be allowed to participate.
- Patients who had received adjuvant chemotherapy and had recurrence during or within 6 months of completion of the adjuvant chemotherapy will be allowed to count the adjuvant therapy as one chemotherapy regimen.
- Progression of disease must be documented on the most recent scan.
- Presence of measurable disease (not required for Phase 1 portion of the trial).
- Retrovirus-associated DNA sequences (RAS) mutation and mismatch repair (MMR) status must be determined (or tissue availability for testing if not already determined)
Key exclusion criteria (17 listed)
- Patients who have previously received TAS-102.
- Grade 2 or higher peripheral neuropathy.
- Symptomatic Central nervous system (CNS) metastases requiring treatment.
- Other active malignancy within the last 3 years (except for non-melanoma skin cancer or a non-invasive/in situ cancer).
- Pregnancy or breast feeding.
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 |
|---|---|---|
| combined TAS-102 and TAS-OXCombination treatment with TAS-102 and oxaliplatin. TAS-102 is an oral medication; oxaliplatin (TAS-OX) is given by infusion. | Drug | combined TAS-102 and oxaliplatin |
Primary outcome
Overall Response Rate
Time frame: up to 30 days following discontinuation of treatment
Overall Response Rate was measured by Response Evaluation Criteria In Solid Tumor (RECIST) 1.1 criteria. Tumors were assessed with CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.".
2 secondary outcomes
Progression Free Survival
Time frame: from the date of start of treatment to the date of first documented progression or any cause of death assessed up to 12 months.
Overall Survival
Time frame: from the date of start of treatment to the date of any cause of death assessed up to 24 months.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 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.
Jeremy S. Kortansky, M.D. principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing combined TAS-102 and TAS-OX in people with Colorectal Neoplasms, run by Yale University 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 21 inclusion and 17 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: finished, as of the sponsor's last update on 20 Jul 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 combined 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.
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?
Yes. Results are posted in the registry (first posted 20 Jul 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?
Overall Response Rate (time frame: up to 30 days following discontinuation of treatment). 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 20 Jul 2021.