Study of Single Agent Idelalisib Followed by Idelalisib in Combination With Chemotherapy in Adults With Metastatic Pancreatic Ductal Adenocarcinoma

Gilead Sciences

Status and phase: Terminated; Phase 1

Conditions: Relapsed/Refractory Pancreatic Ductal Adenocarcinoma; Previously Untreated Pancreatic Ductal Adenocarcinoma

Treatments: Drug: Nab-paclitaxel; Drug: mFOLFOX6; Drug: Idelalisib

Study type: Interventional

Funder types: Industry

Identifiers

NCT02468557

GS-US-385-1577

Details and patient eligibility

About

The primary objective of this study is to evaluate the safety of single agent idelalisib and to evaluate safety and define the maximum tolerated dose (MTD) of idelalisib in combination with chemotherapy in adults with metastatic pancreatic ductal adenocarcinoma.

Enrollment: 16 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• The presence of metastatic pancreatic adenocarcinoma plus 1 of the following:

  • Histological diagnosis of pancreatic adenocarcinoma confirmed pathologically, OR
  • Pathologist confirmed histological/cytological diagnosis of adenocarcinoma consistent with pancreas origin

• Measurable disease per response evaluation criteria in solid tumors (RECIST) v1.1

• Prior systemic chemotherapy treatment for metastatic pancreatic ductal adenocarcinoma (Arm: idelalisib single agent only)

• Received one prior line of chemotherapy for metastatic pancreatic ductal adenocarcinoma (Arm: idelalisib + mFOLFOX6 only)

• Adequate organ function defined as follows:

  • Hepatic: Total bilirubin ≤ 1.25 x upper limit of normal (ULN) (Arm: idelalisib + nab-paclitaxel ); total bilirubin ≤1.5 x ULN (Arm: single agent idelalisib and Arm: idelalisib + mFOLFOX6); aspartate transaminase (AST) serum glutamic oxaloacetic transaminase (SGOT), alanine transaminase (ALT) serum glutamic pyruvic transaminase (SGPT) < 2.5 x ULN, and albumin > 3.0 g/dL
  • Hematological: absolute neutrophil count (ANC) > 1,500 cells/cubic millimetre (m^3), platelet > 100,000 cells/mm^3, hemoglobin > 9.0 grams/decilitre (g/dL)
  • Renal: Serum creatinine ≤ 1.5 x ULN OR calculated creatinine clearance (CrCl) > 30 millilitre (ml)/min as calculated by the Cockcroft-Gault method

• Able to comprehend and willing to sign the written informed consent form

Key Exclusion Criteria:

• Currently or previously treated with biologic, or immunotherapy
• Currently or previously treated with conventional chemotherapy, or other agents for metastatic pancreatic ductal adenocarcinoma (Arm: idelalisib + nab-paclitaxel only)
• Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of enrollment
• Known human immunodeficiency viruses (HIV) infection
• History of a concurrent or second malignancy except for adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate-specific antigen for ≥ 1 year prior to enrollment, adequately treated Stage 1 or 2 non-pancreatic cancer currently in complete remission, or any other non-pancreatic cancer that has been in complete remission for ≥ 5 years
• Diagnosis of pancreatic islet neoplasm, acinar cell carcinoma, non-adenocarcinoma (eg, lymphoma, sarcoma), adenocarcinoma originating from the biliary tree or cystadenocarcinoma
• History of serious allergic reaction, including anaphylaxis and toxic epidermal necrolysis
• Presence of peripheral neuropathy ≥ Grade 2 (Arm: idelalisib + nab-paclitaxel and Arm: idelalisib + mFOLFOX6)
• Documented myocardial infarction or unstable/uncontrolled cardiac disease (eg, unstable angina, congestive heart failure [New York Heart Association > Class III]) within 6 months or enrollment
• Known hypersensitivity to idelalisib, its metabolites, or formulation excipients
• Known hypersensitivity to nab-paclitaxel (Arm: idelalisib + nab-paclitaxel), their metabolites, or formulation excipients
• Known hypersensitivity to 5-fluorouracil, leucovorin, or oxaliplatin (Arm: idelalisib + mFOLFOX6), their metabolites, or formulation excipients

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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16 participants in 3 patient groups

Idelalisib 150 mg

Experimental group

Description:

Participants were administered with idelalisib (IDL) 150 mg tablets orally, twice daily (morning and evening) for 8 weeks.

Treatment:

Drug: Idelalisib

Idelalisib + nab-paclitaxel

Experimental group

Description:

Participants will receive escalating doses of idelalisib at a dose level of up to 150mg + nab-paclitaxel.

Treatment:

Drug: Idelalisib

Drug: Nab-paclitaxel

Idelalisib + mFOLFOX6

Experimental group

Description:

Participants will receive escalating doses of idelalisib at a dose level of up to 150mg + mFOLFOX6.

Treatment:

Drug: mFOLFOX6

Drug: Idelalisib