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Malignant Neoplasms of Digestive OrgansPhase 2NCT03428126

Study of Durvalumab (MEDI4736) (Anti-PD-L1) and Trametinib (MEKi) in MSS Metastatic Colon Cancer

A Phase 2 study testing Durvalumab and Trametinib in people with Malignant Neoplasms of Digestive Organs and Colorectal Cancer, run by M.D. Anderson Cancer Center at 1 site in United States.

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

The goal of this clinical research study is to learn if durvalumab and trametinib can help to control microsatellite stable (MSS) colorectal cancer. The safety of these drugs will also be studied. This is an investigational study. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Durvalumab and Trametinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
29 participants
Where
1 siteUnited States
Study dates
21 Mar 2018to 5 May 2022
Phase
Phase 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

  • Patients must have histologically or cytologically confirmed metastatic colorectal cancer.
  • Patients must have measurable disease per RECIST v1.1 criteria.
  • Patients must have had at least prior treatment with a fluoropyrimidine and either oxaliplatin or irinotecan.
  • Age >/=18 years. Because no dosing or adverse event data are currently available on the use of this combination in patients <18 years of age, children are excluded from this study.
  • Body weight > 30kg.
  • Life expectancy of greater than 6 months.
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  • ECOG performance status 0-1 (Karnofsky >/=70%).
  • Patients must have normal organ and marrow function as defined below: - Leukocytes >/=3,000/mcL, Absolute neutrophil count >/=1,500/mcL, Hemoglobin >/=9.0g/dL, Platelets >/=75,000/mcL, Total bilirubin < 1.5 X institutional normal limits (subjects with known Gilbert syndrome are eligible with total bilirubin < 3.0 mg/dL), AST(SGOT)/ALT(SGPT) </=2.5 X institutional ULN (</= 5 if liver metastases present), Creatinine within normal institutional limits OR, Creatinine clearance > 40mL/min by Cockcroft-Gault or 24h urine collection.
  • Known MSS status by either IHC or PCR. Known or evaluable BRAF and KRAS status.
  • Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal subjects. Women will be considered post-menopausal if they have been amenorrheic 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 amenorrheic 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).
  • Inclusion #10 cont'd -- Women >/=50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately and will be removed from the study.
  • Ability to understand and the willingness to sign a written informed consent document.
  • Willingness to have 2 tumor biopsies; the first before and the second while on therapy (optional for all patients and may become mandatory in order to ensure 15 patients at MTD have paired biopsies).

Who cannot join

  • Patients who have had chemotherapy within 2 weeks prior to first dose of study drug.
  • Any unresolved toxicity NCI CTCAE Grade >/=2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria: -- Subjects with Grade >/=2 neuropathy will be evaluated on a case-by-case basis after consultation with the Principal investigator.-- Subjects with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Principal investigator.
  • Patients may not be receiving any other investigational agents.
  • Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of study medication. Note: Local surgery of isolated lesions for palliative intent is acceptable.
  • Patients with known brain metastases or leptomeningeal carcinomatosis will be excluded from this clinical trial. Patients with suspected brain metastases at screening should have an MRI (preferred) or CT each preferably with IV contrast of the brain prior to study entry.
  • Mean QT interval corrected for heart rate (QTc) >/= 470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia's Correction.
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  • History of pneumonitis or interstitial lung disease (ILD).
  • History of allogenic organ transplantation.
  • Subjects with active, known, or suspected autoimmune disease including patients with a history of inflammatory bowel disease (ulcerative colitis or Crohn's disease); patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis (e.g., Wegener's granulomatosis), and central nervous system or motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre Syndrome, myasthenia gravis, multiple sclerosis). Subjects with vitiligo, type I diabetes mellitus, Grave's disease, Hashimoto thyroiditis, psoriasis, and other mild autoimmune disease not requiring systemic treatment are permitted to enroll at the discretion of the investigator.
  • Subjects with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
  • Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Subjects, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP.
  • Prior exposure to T cell checkpoint inhibitor therapies.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirements, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
  • History of active primary immunodeficiency.
  • Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice for patients suspected of having active infection), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Subjects with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Subjects positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  • Female subjects who are pregnant or breastfeeding or male or female subjects of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of study medications.
  • Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Phase II Study of Durvalumab (MEDI4736) (Anti-PD-L1) and Trametinib (MEKi) in MSS Metastatic Colon Cancer

The goal of this clinical research study is to learn if durvalumab and trametinib can help to control microsatellite stable (MSS) colorectal cancer. The safety of these drugs will also be studied.

This is an investigational study. Durvalumab is FDA approved and commercially available for the treatment of previously treated advanced bladder cancer. Trametinib is FDA approved in combination with another drug called dabrafenib for the treatment of unresectable or metastatic melanoma with BRAF V600E or BRAF V600K.

It is investigational to use durvalumab and trametinib to treat MSS colorectal cancer.

Up to 56 participants will be enrolled in this study. All will take part at MD Anderson.

Read the detailed description

Study Drug Administration:

Each cycle is 28 days.

Participant will take trametinib tablets by mouth every day with at least 8 ounces of water. Each dose should be taken at about the same time each day, 1 hour before or 2 hours after a meal. Participant should not crush, cut, or chew the tablets. If participant misses a dose of trametinib, participant may take the tablets as soon as participant remembers but only if participant's next scheduled dose is at least 12 hours later. If participant's next scheduled dose is less than 12 hours, participant should wait and take participant's next dose as scheduled.

Participant will take trametinib alone for the first 7 days of the study and then participant will begin receiving it in combination with durvalumab.

Every 4 weeks, participant will receive durvalumab by vein over about 60 minutes.

Length of Treatment:

Participant will be able to receive the study drugs for as long as the doctor thinks it is in participant's best interest. Participant no longer will take the study drugs if intolerable side effects occur or if the study doctor decides that the drugs are no longer working.

It is expected that participation in this study may last about 12 months.

Participation in this study will be over after follow-up.

Study Visits:

On Day 1 of Weeks 0, 2, 4, 6, 12, and then every 4 weeks after that (Weeks 16, 20, 24, and so on):

  • Participant will have a physical exam.
  • Blood (about 6 tablespoons) will be drawn for routine tests, immune system testing, and biomarker testing.
  • If participant had a biopsy at screening, participant will have another biopsy during Week 4 to check the status of the disease and for biomarker testing. Depending on when participant joins the study, this biopsy may be optional.

On Day 1 of Week 8:

  • Participant will have a physical exam.
  • Blood (about 6 tablespoons) will be drawn for routine tests, immune system testing, and biomarker testing.
  • Participant will have a CT scan.

On Day 1 of Week 16 and then every 8 weeks after that (Weeks 24, 32, 40, and so on), participant will have a CT scan.

End-of-Treatment:

About 28 days after participant's last dose of study drugs, participant will have a physical exam.

Follow-Up:

After participant's end-of-treatment visit, participant will be called by the study staff every 3 months for up to 18 months to ask how participant is doing. Each call should last about 5-10 minutes.

Being tested
Durvalumab, Trametinib
Keywords
Malignant neoplasms of digestive organs, Colorectal Cancer, Colon Cancer, Durvalumab, MEDI4736, Trametinib, GSK1120212
Medical subject headings
Colorectal Neoplasms, Colonic Neoplasms

What participants receive

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

  • DurvalumabDrug

    Also called MEDI4736

    Dose Escalation and Dose Expansion Dose: 1500 mg by vein every 4 weeks in a 28 day cycle.

  • TrametinibDrug

    Also called GSK1120212

    Dose Escalation Starting Dose: 2mg by mouth daily in a 28 day cycle.

    Dose Expansion Dose: MTD from Dose Escalation.

Study groups in NCT03428126
Study groupRoleWhat they receive
Durvalumab + TrametinibExperimentalParticipants take Trametinib tablets by mouth every day. Trametinib taken alone for the first 7 days of the study then participants begin receiving it in combination with Durvalumab. Participants receive Durvalumab by vein every 4 weeks. Each cycle is 28 days.
Receives: Drug: Durvalumab; Drug: Trametinib

What is being measured

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

  1. Immune-related Best Overall Response Rate.

    Best overall response rate (CR+PR) by immune-related response rate.

    Measured: From Baseline to 2 years

Secondary outcomes (3)

  1. Progression Free Survival as Determined by irRC

    The Kaplan-Meier method GraphPad software, V.8 was used for statistical analyses.

    Measured: From Baseline to up to 2 years

  2. Overall Survival

    The Kaplan-Meier method GraphPad software, V.8 was used for statistical analyses.

    Measured: From Baseline to 2 years

  3. Disease Control Rate

    Disease control rate (DCR) describes the percentage of patients with advanced cancer whose therapeutic intervention has led to a complete response, partial response, or stable disease.

    Measured: From Baseline to 2 years.

Timeline

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

  1. First posted9 Feb 2018
  2. Study start21 Mar 2018
  3. Primary completion5 May 2022
  4. Study completion5 May 2022

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
29 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03428126
Sponsor's protocol ID
2017-0514
Other IDs
NCI-2018-00911
Status last verified
Jun 2023
First submitted
5 Feb 2018
Last updated
15 Jun 2023
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Johnson B, Haymaker CL, Parra ER, Soto LMS, Wang X, Thomas JV, Dasari A, Morris VK, Raghav K, Vilar E, Kee BK, Eng C, Parseghian CM, Wolff RA, Lee Y, Lorenzini D, Laberiano-Fernandez C, Verma A, Lang W, Wistuba II, Futreal A, Kopetz S, Overman MJ. Phase II study of durvalumab (anti-PD-L1) and trametinib (MEKi) in microsatellite stable (MSS) metastatic colorectal cancer (mCRC). J Immunother Cancer. 2022 Aug;10(8):e005332. doi: 10.1136/jitc-2022-005332.

    PubMed 36007963

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Durvalumab and Trametinib in people with Malignant Neoplasms of Digestive Organs and Colorectal Cancer, run by M.D. Anderson Cancer Center 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 14 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 15 Jun 2023. 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 phase mean?

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 15 Jun 2023). 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?

Immune-related Best Overall Response Rate. (time frame: From Baseline to 2 years). 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 NCT03428126, which also lists 1 linked publication.

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 15 Jun 2023.

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