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Extensive-stage Small Cell Lung CancerPhase 1NCT03085849

SGI-110 Plus Durvalumab/Tremelimumab in SCLC

A Phase 1 study testing Durvalumab, Tremelimumab and SGI-110 in people with Extensive-stage Small Cell Lung Cancer, run by Catherine Shu 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 purpose of this study is to determine if a combination of investigational agents is safe to give to people with small cell lung cancer (SCLC) after standard chemotherapy has been attempted. Read more about this study

Who is it for?
Ages 18 to 99 years
Conditions the study is for
Extensive-stage Small Cell Lung Cancer
What is being tested?
Durvalumab, Tremelimumab and SGI-110
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2 participants
Where
1 siteUnited States
Study dates
15 Dec 2017to 26 Nov 2018
Phase
Phase 1
Are there results?
None posted in the registry

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 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • For inclusion in the study, patients should fulfill the following criteria:
  • Written informed consent and any locally-required authorization (e.g., HIPAA in the USA, EU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
  • Age ≥ 18 years at time of study entry
  • Eastern Cooperative Oncology Group (ECOG performance status of 0 or 1)
  • Life expectancy of ≥ 12 weeks
  • Adequate normal organ and marrow function as defined below Hemoglobin ≥ 9.0 g/dL Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (> 1500 per mm3) Platelet count ≥ 100 x 109/L (>100,000 per mm3) Serum total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (for patients with a diagnosis of Gilbert's syndrome, direct bilirubin ≤ 1.5 x ULN) AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤ 5x ULN
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  • Serum creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:
  • Males:
  • Creatinine CL (mL/min) = Weight (kg) x (140 - Age) . 72 x serum creatinine (mg/dL)
  • Females:
  • Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 72 x serum creatinine (mg/dL)
  • Females of childbearing potential who are sexually active with a non-sterilized male partner must use a highly effective method of contraception from the time of screening, and must agree to continue using such precautions for 180 days after the final dose of investigational product. Cessation of contraception after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. Female subjects must also refrain from egg cell donation for 180 days after the final dose of investigational product.
  • Females of childbearing potential are defined as those who are not surgically sterile (i.e. bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or those who are not postmenopausal (defined as 12 months with no menses with postmenopausal gonadotropin levels [luteinizing hormone and follicle-stimulating hormone], or estradiol levels within the postmenopausal range according to local guidelines without an alternative medical cause).
  • A highly effective method of contraception is defined as one that results in a low failure rate (i.e. less than 1% per year) when used consistently and correctly.
  • Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
  • Subjects must have a histologically confirmed diagnosis of small cell lung carcinoma. A fresh, pre-treatment tumor biopsy will be required to evaluate tumor infiltrating lymphocytes, PD-L1 IHC staining, methylation status, etc. as outlined in the study timeline. All subjects are also required to have a C1D8 (or C2D8) biopsy.
  • Subjects must have extensive-stage disease (by NCCN criteria) that is progressive or relapsed after platinum-based chemotherapy.
  • Tumor burden must be radiographically measurable by RECIST criteria.
  • At time of Day 1 of the study, subjects with central nervous system metastases must have been treated and must be asymptomatic and meet the following:
  • No concurrent treatment, inclusive of but not limited to surgery, radiation, and/or corticosteroids
  • Neurologic stability (lack of signs and symptoms greater than baseline prior to XRT) until the time of dosing
  • For radiation treatment, there should be at least 14 days between the last day of stereotactic radiosurgery or gamma-knife treatment and Day 1 of protocol treatment. For WBRT, there should be at least 28 days between last day of WBRT and Day 1 of protocol treatment.
  • Note: patients with leptomeningeal disease or cord compression are excluded from the study.

Who cannot join

  • Subjects should not enter the study if any of the following exclusion criteria are fulfilled:
  • Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
  • Previous enrollment in the present study.
  • Participation in another clinical study with an investigational product during the last 4 weeks.
  • Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an anti-CTLA4, including tremelimumab
  • Any previous treatment with a hypomethylating agent, including decitabine, azacitidine, or SGI-110.
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  • History of another primary malignancy except for:
  • Malignancy treated with curative intent and with no known active disease ≥ 5 years before the first dose of study drug and of low potential risk for recurrence
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
  • Adequately treated carcinoma in situ without evidence of disease e.g., cervical cancer in situ
  • Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, gamma-knife, other investigational agent) ≤ 14 days prior to the first dose of study drug. For WBRT, the washout period is 28 days. Local treatment of isolated lesions for palliative RT (by radiotherapy, for example) is acceptable.
  • Mean QT interval corrected for heart rate (QTc) ≥ 470 ms calculated from electrocardiogram (in triplicate, if applicable) using Fredericia's Correction
  • Liver cirrhosis or chronic liver disease Childs-Pugh B or C.
  • Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab or tremelimumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid.
  • Receipt of the tyrosine kinase inhibitor sunitinib within 90 days before the first dose of study therapy.
  • Any unresolved toxicity ( > CTCAE grade 2) from previous anti-cancer therapy.
  • Any prior Grade ≥ 3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1
  • Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
  • Active or prior documented history of pneumonitis or interstitial lung disease.
  • Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
  • History of primary immunodeficiency
  • History of allogeneic organ transplant
  • History of hypersensitivity to durvalumab, tremelimumab, SGI-110, or any excipient.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent
  • Known history of active tuberculosis
  • Leptomeningeal carcinomatosis or cord compression
  • Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab or tremelimumab
  • Female subjects who are pregnant or breast-feeding, or male or female patients of reproductive potential who are not willing to employ a highly effective method of contraception from screening to 180 days after the last dose of investigational therapy.
  • Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
  • Symptomatic or uncontrolled brain metastases requiring concurrent treatment (surgery, RT, corticosteroids)
  • Subjects with uncontrolled seizures.
  • Concomitant use of drugs with laxative properties and/or herbal/natural remedies for constipation. These agents should be avoided for 90 days after the last dose of investigational therapy, given the potential for exacerbation of diarrhea.
  • Known significant mental illness or other conditions such as active alcohol or other substance abuse/addiction that, in the opinion of the investigator, predisposes the subject to high risk of noncompliance with the protocol.
  • Procedures for withdrawal of incorrectly enrolled patients are presented in Section 5.5.1. If a patient withdraws from participation in the study, then his or her enrollment/randomization code cannot be reused. Withdrawn patients will not be replaced.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Columbia University Medical Center

    New York, New York, 10032

Other trials in United States

About this study

Official title: A Phase I Study Evaluating the Safety and Efficacy of SGI-110 Followed by Combined Durvalumab Plus Tremelimumab in Subjects With Extensive-stage Small Cell Lung Cancer (ES-SCLC)

The purpose of this study is to determine if a combination of investigational agents is safe to give to people with small cell lung cancer (SCLC) after standard chemotherapy has been attempted. Subjects enrolled in this trial will receive 3 investigational drugs: SGI-110 (guadecitabine), durvalumab (MEDI4736) and tremelimumab.

Read the detailed description

SCLC accounts for approximately 15% of new cases of lung cancer, and an estimated 33,000 cases are expected to be diagnosed in the United States in 2016. Compared to NSCLC, SCLC typically has a more rapid doubling time, a higher growth fraction, and earlier development of distant metastases. Patients with limited stage (LS) disease are treated with curative intent using definitive, concurrent chemotherapy and thoracic radiotherapy. For patients with extensive stage (ES) disease, systemic chemotherapy can prolong survival in most cases, however long-term survival is rare. Despite the activity of several agents in SCLC, an etoposide plus platinum (i.e. cisplatin) doublet regimen remains the standard of care in the first-line setting because of its higher activity compared to other chemotherapy regimens, as well as the ease of combining it with radiation. Initial response rates may be as high as 70-90% in LS-SCLC and 50-70% in ES-SCLC. However, the disease typically recurs rapidly which is reflected by median survival rates of 9 to 11 months for ES-SCLC and a 2-year survival rate of less than 5%.

This study has a 3 + 3 design that will be used to assess the safety of SGI-110 given prior to flat doses of durvalumab (1500 mg) and tremelimumab (75 mg). The starting dose of SGI-110 will be 30 mg/m2 (dose level 0) and the target dose that is predicted to be safe and most effective will be 45 mg/m2 (dose level 1). These doses have been chosen based on safety and efficacy data from phase 1 clinical trials in other solid tumors, as described above. Patients enrolled in any given dose level will be evaluated for safety (adverse events monitoring) and efficacy. There will be mandatory pre- and on-treatment tumor biopsies performed in alternating fashion on cycle 1 day 8 +/- 2 days or cycle 2 day 8 +/- 2 days. The dose-limiting toxicity (DLT) observation period will last for 4 weeks (28 days) and ends on C2D1. Delayed serious immune-mediated adverse events will also be monitored but will not be considered dose limiting toxicities.

Being tested
Durvalumab, Tremelimumab, SGI-110
Medical subject headings
Small Cell Lung Carcinoma

What participants receive

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

  • DurvalumabDrug

    Also called MEDI4736

    1500 mg IV on day 8 (flat dose) until progression

  • TremelimumabDrug

    Also called CP-675,206

    75 mg IV on day 8 (flat dose) x 4 doses

  • SGI-110Drug

    Also called Guadecitabine

    SC daily for 5 days (days 1-5) until progression or toxicity

    Dose escalation scheme:

    Dose level -1 - SGI-110 20 mg/m2 SC daily; Dose level 0 - SGI-110 30 mg/m2 SC daily; Dose level 1 - SGI-110 45 mg/m2 SC daily; and SGI-110 given on days 1-5 of every 28 day cycle

Study groups in NCT03085849
Study groupRoleWhat they receive
TreatmentExperimentalSubjects with ES-SCLC, progressive after platinum-based first-line chemotherapy will receive SGI-110 followed by combined durvalumab plus tremelimumab. 1. Dose escalation phase: 6-12 patients 2. MTD expansion cohort: 10 patients
Receives: Drug: Durvalumab; Drug: Tremelimumab; Drug: SGI-110

What is being measured

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

  1. Maximum tolerated dose (MTD) of SGI-110

    Defined as the highest dose cohort for SGI-110 with a rate of dose limiting toxicity (DLT) <33%.

    Measured: Approximately 24 to 48 weeks

Secondary outcomes (5)

  1. Rate of treatment related adverse events

    Defined by the percentage of patients receiving study treatment and experiencing grade 3-4 treatment related adverse events.

    Measured: Up to 90 days after last study dose

  2. Overall Response Rate (ORR)

    Defined by the proportion of patients with tumor size reduction of a predefined amount and for a minimum time period.

    Measured: Up to 12 months after last study dose

  3. Median Progression Free Survival (mPFS)

    The length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse. Estimated using the Kaplan-Meier method in number of weeks.

    Measured: Up to 24 months after last study dose

  4. Median Overall Survival (mOS)

    The length of time from the start of treatment for a disease, such as cancer, that half of the patients in a group of patients diagnosed with the disease are still alive. Estimated using the Kaplan-Meier method in number of weeks.

    Measured: Up to 24 months after last study dose

  5. Median Duration of Response (mDOR)

    Duration of overall response is measured from the time measurement criteria are met for complete response or partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).

    Measured: Up to 12 months after last study dose

Timeline

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

  1. First posted21 Mar 2017
  2. Study start15 Dec 2017
  3. Primary completion26 Nov 2018
  4. Study completion26 Nov 2018

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
2 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03085849
Sponsor's protocol ID
AAAQ8257
Status last verified
Dec 2018
First submitted
9 Mar 2017
Last updated
10 Dec 2018
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016 Jan-Feb;66(1):7-30. doi: 10.3322/caac.21332. Epub 2016 Jan 7.

    PubMed 26742998

  • Chute JP, Chen T, Feigal E, Simon R, Johnson BE. Twenty years of phase III trials for patients with extensive-stage small-cell lung cancer: perceptible progress. J Clin Oncol. 1999 Jun;17(6):1794-801. doi: 10.1200/JCO.1999.17.6.1794.

    PubMed 10561217

  • Janne PA, Freidlin B, Saxman S, Johnson DH, Livingston RB, Shepherd FA, Johnson BE. Twenty-five years of clinical research for patients with limited-stage small cell lung carcinoma in North America. Cancer. 2002 Oct 1;95(7):1528-38. doi: 10.1002/cncr.10841.

    PubMed 12237922

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Durvalumab, Tremelimumab and SGI-110 in people with Extensive-stage Small Cell Lung Cancer, run by Catherine Shu 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 23 inclusion and 34 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 10 Dec 2018. 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 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.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Maximum tolerated dose (MTD) of SGI-110 (time frame: Approximately 24 to 48 weeks). 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 NCT03085849, which also lists 3 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 10 Dec 2018.

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