Study of Durvalumab and Guadecitabine in Advanced Kidney Cancer

NCT03308396 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: BTCRC-GU16-043
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 5

Brief Summary

This is a single arm, multi-centre (via Big Ten Cancer Research Consortium) phase Ib/II study of patients treated with durvalumab 1500 mg IV q 4 weeks in combination with guadecitabine at the recommended phase 2 dose subcutaneously for 5 consecutive days. Eligible patients will have metastatic RCC with a clear cell component, ECOG performance status of 0-1, have received 0-1 prior therapy but no prior anti-PD-1/PD-L1/CTLA4 (Cohort 1, 36 subjects). Study treatment could potentially continue for up to 13 cycles (52 weeks).

Conditions

Advanced Kidney Cancer; Kidney Cancer; Clear Cell Renal Cell Carcinoma

Keywords

Durvalumab; Guadecitabine

Outcome Measures

Primary Outcomes (2)

• Phase Ib: Dose limiting toxicities will be assessed to determine if the trial is stopped before the Phase II portion.

  Number of patients with dose-limiting toxicity (DLT) of the combination of durvalumab and guadecitabine

  28 days/First cycle

• Objective response rate

  Objective response rate (complete response (CR) + partial response (PR)) by RECIST 1.1 in Cohort 1

  1 year

Secondary Outcomes (7)

• Phase II: Overall Survival (OS)

  2 years

• Phase II: Duration of Response (DoR)

  2 years

• Phase II: Progression-free survival (PFS)

  2 years

• Phase II: Clinical benefit rate (CBR)

  2 years

• Phase II: Complete response (CR) proportion

  2 years

Study Arms (1)

Single Arm

EXPERIMENTAL

This is a non-randomized, single arm, open label Phase Ib/II study. Phase Ib: Days 1-5 Guadecitabine: * Dose 0: 60 mg/m\^2 * Dose -1: 45 mg/m\^2 Phase II: Days 1-5 Guadecitabine (at Ph II dose) Day 8 Durvalumab (1500 mg IV) Day 8 Durvalumab (1500 mg IV)

Drug: Guadecitabine; Drug: Durvalumab

Interventions

Guadecitabine DRUG

Days 1-5 Dose 0: 60 mg/m\^2 Dose -1: 45 mg/m\^2

Also known as: SGI-110

Single Arm

Durvalumab DRUG

Day 8 Durvalumab (1500 mg IV)

Also known as: MEDI4736

Single Arm

Eligibility Criteria

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

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information.
• ECOG Performance Status 0-1 within 28 days prior to registration.
• Histological diagnosis of clear cell renal cell carcinoma (pure or mixed) with radiologic or histologic evidence of metastatic disease.
• At least 1 lesion, not previously irradiated that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have a short axis ≥ 15mm) with a computed tomography (CT) or magnetic resonance imaging (MRI) and that is suitable for accurate repeated measurements as per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) guidelines.
• For cohort 1, subjects may have received up to 1 and no more than 1 prior line of systemic therapy (not counting any neoadjuvant/adjuvant therapy) including anti-VEGF, VEGFR inhibitor, MET inhibitor or mTOR inhibitor for metastatic disease. They cannot have received any prior anti-PD-1/PD-L1/CTLA4 therapy including durvalumab.
• For cohort 2, subjects may have received up to 2 prior systemic therapies which should include 1 (and only 1) prior anti-PD-1/PD-L1 therapy but did not have an objective response to the prior anti-PD-1/Pd-L1 therapy. The treating investigator must document that the patient did not have an objective response to prior anti-PD-1/PD-L1 therapy. They may have received prior anti-CTLA4 therapy.
• Subjects may not have had radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug.
• Prior cancer treatment must be completed at least 14 days prior to study registration and the subject must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to ≤Grade 1 or baseline.
• Demonstrate adequate organ function as defined in the table below; all screening labs to be obtained within 28 days prior to registration:
• Hematological:
• White blood cell (WBC) ≥ 3 K/mm\^3
• Absolute Neutrophil Count (ANC) ≥ 1.5 K/mm\^3
• Hemoglobin (Hgb) ≥ 9 g/dL
• Platelets (Plt) ≥ 100,000/mm\^3
• Renal:

You may not qualify if:

• Subjects meeting any of the criteria below may not participate in the study:
• Active infection requiring systemic therapy.
• Brain metastases or spinal cord compression. 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. Patients whose brain metastases have been treated may be considered if they have completed their treatment for brain metastasis at least 4 weeks prior to study registration provided they show radiographic stability (defined as 1 brain image, obtained after treatment to the brain metastases). In addition, any neurologic symptoms that developed either as a result of the brain metastases or their treatment must have resolved or be stable without the use of steroids for at least 14 days prior to the start of treatment.
• Pregnant or breastfeeding
• 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 IP 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.
• Treatment with any investigational drug within 14 days prior to study registration.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], celiac disease, irritable bowel disease, or other serious gastrointestinal chronic conditions associated with diarrhea, systemic lupus erythematosus, sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]) within the last 3 years prior to study registration. The following are exceptions to this criterion: The following are exceptions to this criterion:
• Subjects with vitiligo or alopecia.
• Subjects with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement.
• Any chronic skin condition that does not require systemic therapy.
• Subjects without active disease in the last 5 years may be included but only after consultation with the study physician.
• Subjects with celiac disease controlled by diet alone.

Sponsors & Collaborators

• Ajjai Alva, MD: lead
• AstraZeneca: collaborator
• Big Ten Cancer Research Consortium: collaborator

Study Sites (5)

Univerisity of Illinois Cancer Center

Chicago, Illinois, 60612, United States

Location

University of Iowa Hosptials and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Penn State Cancer Institute

Hershey, Pennsylvania, 17033, United States

Location

Related Links

• Big Ten Cancer Research Consortium Website

MeSH Terms

Conditions

Kidney Neoplasms; Carcinoma, Renal Cell

Interventions

guadecitabine; durvalumab

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Officials

• Ajjai Alva, M.D.

  University of Michigan

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Open-label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Model Details: Phase Ib/II

Study Record Dates

• First Submitted: October 9, 2017
• First Posted: October 12, 2017
• Study Start: December 19, 2017
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2023
• Last Updated: February 17, 2022

Record last verified: 2022-02

Locations

US (5)