SGI-110 Plus Durvalumab/Tremelimumab in SCLC

NCT03085849 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: AAAQ8257
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief 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. Subjects enrolled in this trial will receive 3 investigational drugs: SGI-110 (guadecitabine), durvalumab (MEDI4736) and tremelimumab.

Conditions

Extensive-stage Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (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%.

  Approximately 24 to 48 weeks

Secondary Outcomes (5)

• Rate of treatment related adverse events

  Up to 90 days after last study dose

• Overall Response Rate (ORR)

  Up to 12 months after last study dose

• Median Progression Free Survival (mPFS)

  Up to 24 months after last study dose

• Median Overall Survival (mOS)

  Up to 24 months after last study dose

• Median Duration of Response (mDOR)

  Up to 12 months after last study dose

Study Arms (1)

Treatment

EXPERIMENTAL

Subjects 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

Drug: Durvalumab; Drug: Tremelimumab; Drug: SGI-110

Interventions

Durvalumab DRUG

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

Also known as: MEDI4736

Treatment

Tremelimumab DRUG

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

Also known as: CP-675,206

Treatment

SGI-110 DRUG

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

Also known as: Guadecitabine

Treatment

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.
• A) 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).
• B) 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Catherine Shu: lead

Study Sites (1)

Columbia University Medical Center

New York, New York, 10032, United States

Location

Related Publications (3)

• 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.

  PMID: 26742998 BACKGROUND

• 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.

  PMID: 10561217 BACKGROUND

• 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.

  PMID: 12237922 BACKGROUND

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

durvalumab; tremelimumab; guadecitabine

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Catherine Shu, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: March 9, 2017
• First Posted: March 21, 2017
• Study Start: December 15, 2017
• Primary Completion: November 26, 2018
• Study Completion: November 26, 2018
• Last Updated: December 10, 2018

Record last verified: 2018-12

Locations

US (1)