Study of Sotorasib Combined With Chemotherapy for Second Line Treatment of Pancreas Cancer

NCT05251038 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: HCRN GI21-499
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicenter, non-randomized, open-label, phase Ib/II study to evaluate the safety, tolerability and efficacy of sotorasib in combination with chemotherapy for patients with advanced KRAS p.G12C mutant pancreatic cancer with progression of disease after first line treatment. There will be a safety lead in to determine the safety and tolerability of the sotorasib in combination with standard chemotherapy. A Simon two-stage design will be employed to evaluate the efficacy of sotorasib in combination with standard of care second line chemotherapy.

Conditions

Pancreatic Cancer; Unresectable Pancreatic Cancer; Metastatic Pancreatic Cancer; KRAS P.G12C

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Clinical activity will be assessed by overall response rate (ORR). ORR is defined as the percentage of patients whose best response is Complete Response (CR) plus those with Partial Response (PR) based on RECIST 1.1.

  2 years

Secondary Outcomes (5)

• Assess Adverse Events

  2 months

• Progression Free Survival (PFS)

  6 months, 1 year, and 2 years

• Duration of Response (DoR)

  2 years

• Disease Control Rate (DCR)

  2 years

• Overall Survival (OS)

  2 years

Study Arms (1)

Experimental Group

EXPERIMENTAL

Patients will either receive a combination of: Sotorasib + Liposomal Irinotecan (nal-IRI) + 5 Fluorouracil (5FU) + Leucovorin (LV) OR Sotorasib + Gemcitabine (GEM) + Nab-paclitaxel \*The combination of therapy received is based on the participants prior therapy and of the discretion of their treating physician

Drug: Sotorasib; Drug: Liposomal Irinotecan (nal-IRI); Drug: 5 Fluorouracil (5FU); Drug: Leucovorin (LV); Drug: Gemcitabine (GEM); Drug: Nab paclitaxel

Interventions

Sotorasib DRUG

Intervention instruction outlined in protocol

Also known as: Lumakras

Experimental Group

Liposomal Irinotecan (nal-IRI) DRUG

Intervention instruction outlined in protocol

Also known as: Onivyde

Experimental Group

5 Fluorouracil (5FU) DRUG

Per standard of care

Experimental Group

Leucovorin (LV) DRUG

Per standard of care

Experimental Group

Gemcitabine (GEM) DRUG

Per standard of care

Experimental Group

Nab paclitaxel DRUG

Per standard of care

Also known as: Abraxane

Experimental Group

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 prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status of 0-1 within 14 days prior to registration.
• Histological or cytological confirmation of pancreatic cancer per AJCC, 8th edition.
• Unresectable or metastatic pancreatic cancer.
• Measurable disease according to RECIST 1.1 within 28 days prior to registration.
• KRAS p. G12C mutation by CLIA certified molecular testing of tumor biopsy or blood based circulating tumor DNA. NOTE: patients must have KRAS p.G12C molecularly confirmed previously or have archived tissue sent for testing and/or undergo biopsy confirming KRAS p.G12C mutation prior to enrollment.
• Demonstrate adequate organ function as defined in the table below. All screening labs to be obtained within 28 days prior to registration:
• Hematological
• Absolute Neutrophil Count (ANC): ≥ 1.5 x 109/L
• Hemoglobin (Hgb): ≥ 9 g/dL; Transfusion permitted within 1 week
• Platelet Count (Plt): ≥ 100 x 109/L
• Renal
• Calculated creatinine clearance1: ≥ 50 mL/min
• Creatinine (Cr): ≤ 1.5 × upper limit of normal (ULN)

You may not qualify if:

• Subjects meeting any of the criteria below may not participate in the study:
• Receipt of two or more lines of chemotherapy. NOTE: Adjuvant or neoadjuvant therapy would be counted as one line of therapy if recurrence or development of metastatic disease occurred within 6 months of last dose of adjuvant/neoadjuvant therapy.
• Previous treatment with a KRASG12C inhibitor.
• Patient unable to receive nal-IRI/5FU/LV or GEM/nab-paclitaxel as second line chemotherapy for pancreatic cancer.
• Grade 2 or higher neuropathy preventing treatment with abraxane containing regimen.
• History of pneumonitis and/or interstitial lung disease (ILD).
• Active brain metastases and/or carcinomatous meningitis from non-brain tumors. NOTE: Subjects who have had brain metastases resected or have received radiation therapy ending at least 4 weeks prior to study Day 1 are eligible if they meet all of the following criteria: a) residual neurological symptoms grade ≤ 2; b) on stable doses of dexamethasone, if applicable; and c) follow-up magnetic resonance imaging (MRI) performed within 28 days shows no new lesions appearing.
• Active infection requiring antibiotics within 1 week of enrollment.
• Cardiac dysfunction:
• Myocardial Infarction within 6 months of enrollment
• NYHA \> class II CHF
• unstable angina
• arrhythmia requiring medication
• QTc \> 470msec.
• Has a known history of Hepatitis B or C. NOTE: Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. NOTE: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.

Sponsors & Collaborators

• Devalingam Mahalingam: lead
• Amgen: collaborator

Study Sites (1)

Northwestern University

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

sotorasib; irinotecan sucrosofate; Fluorouracil; Leucovorin; Gemcitabine; Taxes; Albumin-Bound Paclitaxel

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Economics; Health Care Economics and Organizations; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Devalingam Mahalingam, MD

  Northwestern University Feinberg School of Medicine

  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: Sponsor Investigator

Study Record Dates

• First Submitted: February 11, 2022
• First Posted: February 22, 2022
• Study Start: September 13, 2022
• Primary Completion: January 31, 2023
• Study Completion: January 31, 2023
• Last Updated: May 11, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)