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Previously Treated Metastatic Colorectal CancerPhase 1/2NCT01896856

Phase I/II Study of SGI-110 With Irinotecan Versus Regorafenib or TAS-102 in Metastatic Colorectal Cancer

A Phase 1/2 study testing SGI-110 Dose Escalation, Regorafenib and TAS-102 in people with Previously Treated Metastatic Colorectal Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 4 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a phase I/II study of the combination of Guadecitabine (SGI-110) and previously treated metastatic colorectal cancer patients. This study will be conducted in two components. First, patients will be enrolled in a phase I study of SGI-110 combined with irinotecan in a standard 3+3 design. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
SGI-110 Dose Escalation, Regorafenib and TAS-102
Could I receive a placebo?
No, everyone receives an active treatment
How many people
118 participants
Where
4 sitesin 2 countries
Study dates
23 Oct 2013to 26 Aug 2019
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 or cytologically confirmed adenocarcinoma of the colon or rectum
  • Phase I only: patients with biopsiable disease amenable to having two research biopsies.
  • Have measurable disease
  • Phase II only: progressed while receiving irinotecan therapy in the metastatic setting. There are no limitations on number of prior therapies in the metastatic setting.
  • Life expectancy of greater than 12 weeks.
  • Eastern Cooperative Oncology Group (ECOG) performance status <1
  • Normal organ and marrow function as defined by study-specified laboratory tests
  • Must use adequate contraception through the study and for 3 months after last dose of study drug.

Who cannot join

  • Chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) of first dose of study drug or who have not recovered from treatment-related adverse events
  • Receiving any other investigational agents
  • Participants with known brain metastases
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to irinotecan, decitabine or SGI-110.
  • Received prior therapy with any hypomethylating agents.
  • 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.
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  • Pregnant or nursing women
  • History of a different malignancy are ineligible with exceptions (disease-free for at least 5 years with low risk for recurrence, cervical cancer in situ, definitively treated early stage prostate cancer, definitively treated breast ductal or lobular carcinoma in situ, and basal cell or squamous cell carcinoma of the skin).
  • HIV-positive individuals on combination antiretroviral therapy
  • Phase II only: previous treatment with regorafenib and TAS-102. If patients have previously received either regorafenib OR TAS-102, they must be able to receive the alternate regimen if randomized to standard of care (Arm B).
  • Hospitalization for an acute medical issue within 4 weeks prior to screening visit
  • Symptomatic bowel obstruction within 6 months prior to enrollment, Patients who undergo surgical correction of obstructing lesion will be eligible within 6 months.

Trial locations and contacts

4 sites in 2 countries.

4 sites in 2 countries

United States3 sites

  • Sidney Kimmel Comprehensive Cancer Center

    Baltimore, Maryland, 21231

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

Netherlands1 site

  • VU Medisch Centrum

    Amsterdam, 1081 HV

Other trials in Netherlands

About this study

Official title: A Phase I Study of SGI-110 Combined With Irinotecan Followed by a Randomized Phase II Study of SGI-110 Combined With Irinotecan Versus Regorafenib or TAS-102 in Previously Treated Metastatic Colorectal Cancer Patients

This is a phase I/II study of the combination of Guadecitabine (SGI-110) and previously treated metastatic colorectal cancer patients. This study will be conducted in two components. First, patients will be enrolled in a phase I study of SGI-110 combined with irinotecan in a standard 3+3 design. After the maximum tolerated dose (MTD) is determined, patients will subsequently be enrolled in a 2:1 randomized phase II study of SGI-110 and irinotecan versus the standard of care regorafenib or Lonsurf (TAS-102).

Being tested
SGI-110 Dose Escalation, Regorafenib, TAS-102, SGI-110, Irinotecan
Keywords
SGI-110, irinotecan, regorafenib, methylation, colorectal, metastatic, TAS-102, lonsurf
Medical subject headings
Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SGI-110 Dose EscalationDrug

    Also called Guadecitabine

    • Dose level 1 (DL1): 45 mg/m^2 administered as a subcutaneous injection
    • Dose level 1G (DL1G): 45 mg/m^2 administered as a subcutaneous injection + growth factor support
    • Dose level -1 (DL-1): 30 mg/m^2 administered as a subcutaneous injection
    • Dose level -1G (DL-1G): 30 mg/m^2 administered as a subcutaneous injection + growth factor support

  • RegorafenibDrug

    Also called Stivarga

    160 mg taken orally

  • TAS-102Drug

    Also called Lonsurf, trifluridine and tipiracil

    35 mg/m^2 taken orally

  • SGI-110Drug

    Also called Guadecitabine

    45 mg/m^2 administered as a subcutaneous injection

  • IrinotecanDrug

    Also called Camptosar

    125 mg/m^2 administered IV

Study groups in NCT01896856
Study groupRoleWhat they receive
Phase 1: Dose EscalationExperimentalSubjects receive SGI-110 on days 1-5 and irinotecan on days 8 and 15 of each 28-day cycle. Various doses of SGI-110 are tested to determine the maximum tolerated dose in combination with irinotecan.
Receives: Drug: SGI-110 Dose Escalation
Phase 2: Arm A SGI-110 + irinotecanExperimentalSubjects receive SGI-110 on days 1-5 and irinotecan on days 8 and 15 of each 28-day cycle. Growth factor support (filgrastim and peg-filgrastim) is given during cycle 1 with option to give additional growth factor support at subsequent cycles per clinician judgement.
Receives: Drug: SGI-110; Drug: Irinotecan
Phase 2: Arm B regorafenib or TAS-102Active comparatorSubjects received either regorafenib or TAS-102 based on physician and patient preference. Subjects that had received one of these standard of care drugs (regorafenib or TAS-102) prior to enrollment received the other on study. Regorafenib taken daily from days 1-21 of each 28-day cycle or TAS-102 taken twice daily on days 1-5 and 8-12 of each 28-day cycle. Subjects who had disease progression on Arm B were given the option to receive Arm A study drugs after a 14 day wash-out period.
Receives: Drug: Regorafenib; Drug: TAS-102; Drug: SGI-110; Drug: Irinotecan

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants Experiencing a Dose Limiting Toxicity

    Number of participants experiencing a Dose Limiting Toxicity (DLT) in each dose level. DLT is defined as any of the following study drug-related toxicities occurring during the first cycle of study drug on study:

    1. grade 4 thrombocytopenia lasting >7days
    2. any grade 3-4 febrile neutropenia
    3. grade 3 or higher non-hematologic toxicity unless it could be managed by supportive treatment
    4. any other clinically significant adverse event which would place subjects at undue safety risk, or results in discontinuation of treatment.

    Measured: 28 days

  2. Progression Free Survival (PFS)

    Progression Free Survival is the time (in months) from start of treatment to progression, clinical deterioration attributed to disease, or death.

    Measured: Up to 12 months

Secondary outcomes (2)

  1. Overall Survival

    Overall Survival is defined as the time (in months) between the start of treatment and death.

    Measured: Up to 3 years

  2. Objective Response Rate

    Objective Response Rate (ORR) is defined as the number of subjects achieving a Complete Response (CR) or Partial Response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. CR = disappearance of all target lesions, PR = at least 30% decrease in the sum of diameters of target lesions.

    Measured: Assessed until disease progression, up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Jul 2013 (estimated)
  2. Study start23 Oct 2013
  3. Primary completion26 Aug 2019
  4. Study completion26 Aug 2019

Resources

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
Randomised
Intervention model
Parallel groups
Model description
In Phase 2, Arm B patients who have disease progression will be given the option to receive Arm A study drugs.
Masking
None (open label)
Enrolment
118 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01896856
Sponsor's protocol ID
J1369
Other IDs
NA_00085870
Status last verified
Aug 2020
First submitted
8 Jul 2013
Last updated
6 Oct 2020
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Lee V, Parkinson R, Zahurak M, Cope L, Cercek A, Verheul H, Gootjes E, Lenz HJ, Iqbal S, Jones P, Baylin S, Rami V, Ahuja N, El Khoueiry A, Azad NS. A phase II study of guadecitabine combined with irinotecan vs regorafenib or TAS-102 in irinotecan-refractory metastatic colorectal cancer patients. Int J Cancer. 2024 May 15;154(10):1794-1801. doi: 10.1002/ijc.34845. Epub 2024 Feb 5.

    PubMed 38312102

  • Sharma A, Vatapalli R, Abdelfatah E, Wyatt McMahon K, Kerner Z, A Guzzetta A, Singh J, Zahnow C, B Baylin S, Yerram S, Hu Y, Azad N, Ahuja N. Hypomethylating agents synergize with irinotecan to improve response to chemotherapy in colorectal cancer cells. PLoS One. 2017 Apr 26;12(4):e0176139. doi: 10.1371/journal.pone.0176139. eCollection 2017.

    PubMed 28445481

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing SGI-110 Dose Escalation, Regorafenib and TAS-102 in people with Previously Treated Metastatic Colorectal Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 4 sites in 2 countries.

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 8 inclusion and 12 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 6 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States, Netherlands. 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 14 Sep 2020). 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?

Number of Participants Experiencing a Dose Limiting Toxicity (time frame: 28 days). The study lists 2 primary outcomes in all. 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 NCT01896856, which also lists 2 linked publications.

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 6 Oct 2020.

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