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Pancreatic CancerPhase 1/2NCT05251038

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

A Phase 1/2 study testing Sotorasib, Liposomal Irinotecan (nal-IRI) and 5 Fluorouracil (5FU) in people with Pancreatic Cancer and Unresectable Pancreatic Cancer, run by Devalingam Mahalingam at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Sotorasib, Liposomal Irinotecan (nal-IRI) and 5 Fluorouracil (5FU)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
13 Sep 2022to 31 Jan 2023
Phase
Phase 1/2
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subject must meet all of the following applicable inclusion criteria to participate in this study:
  • 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.
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  • 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)
  • Hepatic
  • Bilirubin: ≤ 1.5 × upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) : ≤ 2.5 × ULN; if liver metastases are present, ≤ 5 x ULN
  • Alanine aminotransferase (ALT): ≤ 2.5 × ULN; if liver metastases are present, ≤ 5 x ULN
  • Coagulation ---International Normalized Ratio (INR) or Prothrombin Time (PT) or Activated Partial Thromboplastin Time (aPTT): ≤ 1.5 × ULN; this would not apply to patient's on anti-coagulation therapy (which is permitted on study; EXCEPT Warfarin)
  • Progression of disease after first line chemotherapy or recurrent disease either during or < 6 months after last dose of systemic therapy administered for curative intent.
  • Prior cancer treatment (including investigational agents) must be completed at least 2 weeks prior to registration and the subject must have recovered from all reversible acute toxic effects of the regimen (other than alopecia or neuropathy) to Grade ≤ 1 or baseline.
  • Life expectancy > 3 months in the opinion of the investigator.
  • Therapeutic or palliative radiation >/= 2 weeks from registration is allowed provided subject has recovered from all reversible acute toxic effects to Grade </= 1 or baseline.
  • Ability to take oral medications.
  • Females of childbearing potential with a male partner able to father a child must have a negative pregnancy test within 7 days prior to registration. See protocol for definition of childbearing potential.
  • Females of childbearing potential with a male partner able to father a child and male participants able to father a child who have a female partner of childbearing potential must be willing to abstain from heterosexual intercourse or to use effective method(s) of contraception as outlined in protocol.
  • As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.

Who cannot join

  • 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).
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  • 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.
  • Has a known history of Human Immunodeficiency Virus (HIV) infection. NOTE: Subjects with HIV/AIDS with adequate antiviral therapy to control viral load would be allowed if they are stable and have been on treatment for ≥ 4 weeks prior to first dose of study drug(s). Subjects with viral hepatitis with controlled viral load would be allowed while on suppressive antiviral therapy. Testing not required.no testing for HIV is required unless mandated by local health authority.
  • Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen, per treating physician discretion, are not eligible for this trial.
  • History or presence of hematological malignancies unless curatively treated with no evidence of disease ≥ 2 years.
  • Surgery within 28 days of enrollment.
  • Known dihydropyrimidine dehydrogenase deficiency.
  • Use of known CYP3A4 and P-gp sensitive substrates (with a narrow therapeutic window), within 14 days or 5 half-lives of the drug or its major active metabolite, whichever is longer, prior to study Day 1 that was not reviewed and approved by the principal investigator.
  • Use of strong inducers of CYP3A4 (including herbal supplements such as St. John's wort) within 14 days or 5 half-lives (whichever is longer) prior to study day 1 that was not reviewed and approved by the principal investigator.
  • Female subjects who are breastfeeding or who plan to breastfeed while on study and through the timeframe as described in protocol (NOTE: breast milk cannot be stored for future use while the mother is being treated on study). Male participants who plan to donate sperm while on study and through the timeframe as described in protocol.
  • Use of warfarin. NOTE: use of low molecular weight heparin (LMWH) are permitted.
  • Acid reducing agents including proton pump inhibitors (PPIs) and H2 receptor antagonists. Alternative agents to acid reducing agents are permitted. If an acid-reducing agent cannot be avoided, administer sotorasib 4 hours before or 10 hours after acid-reducing agent use.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Northwestern University

    Chicago, Illinois, 60611

Other trials in United States

About this study

Official title: A Phase Ib/II Study of Sotorasib Combined With Chemotherapy for Second Line Treatment of KRAS p. G12C Mutated Advanced Pancreatic Cancer

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.

Being tested
Sotorasib, Liposomal Irinotecan (nal-IRI), 5 Fluorouracil (5FU), Leucovorin (LV), Gemcitabine (GEM)
Medical subject headings
Pancreatic Neoplasms

What participants receive

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

  • SotorasibDrug

    Also called Lumakras

    Intervention instruction outlined in protocol

  • Liposomal Irinotecan (nal-IRI)Drug

    Also called Onivyde

    Intervention instruction outlined in protocol

  • 5 Fluorouracil (5FU)Drug

    Per standard of care

  • Leucovorin (LV)Drug

    Per standard of care

  • Gemcitabine (GEM)Drug

    Per standard of care

  • Nab paclitaxelDrug

    Also called Abraxane

    Per standard of care

Study groups in NCT05251038
Study groupRoleWhat they receive
Experimental GroupExperimentalPatients 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
Receives: Drug: Sotorasib; Drug: Liposomal Irinotecan (nal-IRI); Drug: 5 Fluorouracil (5FU); Drug: Leucovorin (LV); Drug: Gemcitabine (GEM); Drug: Nab paclitaxel

What is being measured

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

  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.

    Measured: 2 years

Secondary outcomes (5)

  1. Assess Adverse Events

    Characterize the safety and tolerability of patients receiving sotorasib combined with chemotherapy for second line treatment of pancreas cancer. Determine safety and tolerability as determined by NCI CTCAE v 5.0

    Measured: 2 months

  2. Progression Free Survival (PFS)

    Determine progression free survival (PFS) including the 6- month, 1- year, 2-year and median progression free survival. PFS is defined from the date from first dose of study drug administration (C1D1) until the date of first documentation of progressive disease by RECIST 1.1 or death from any cause, whichever comes first

    Measured: 6 months, 1 year, and 2 years

  3. Duration of Response (DoR)

    Determine the Duration of Response (DOR). DOR is defined from the date of first documentation of response to treatment, to the date of first documentation of progressive disease by RECIST 1.1 or death, whichever comes first, in patients who experience a response.

    Measured: 2 years

  4. Disease Control Rate (DCR)

    Determine the Disease Control Rate (DCR). DCR is defined as the percentage of patients whose best response is complete response (CR) plus partial response (PR) plus stable disease (SD) by RECIST 1.1.

    Measured: 2 years

  5. Overall Survival (OS)

    Determine Overall Survival (OS). OS is assessed from the date of registration to the study until the date of death from any cause for up to 2 years.

    Measured: 2 years

Timeline

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

  1. First posted22 Feb 2022
  2. Study start13 Sep 2022
  3. Primary completion31 Jan 2023
  4. Study completion31 Jan 2023

Why it stopped: Funder Decision

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05251038
Sponsor's protocol ID
HCRN GI21-499
Status last verified
Feb 2023
First submitted
11 Feb 2022
Last updated
11 May 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Sotorasib, Liposomal Irinotecan (nal-IRI) and 5 Fluorouracil (5FU) in people with Pancreatic Cancer and Unresectable Pancreatic Cancer, run by Devalingam Mahalingam 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 29 inclusion and 25 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: withdrawn, as of the sponsor's last update on 11 May 2023. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 was withdrawn before enrolling participants, so there are no results.

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?

Objective Response Rate (ORR) (time frame: 2 years). 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 NCT05251038.

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 11 May 2023.

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