Adavosertib and Gemcitabine in Advanced Pancreatic

NCT05212025 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 21-620
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is being done to test the safety and effectiveness of combining Adavosertib and Gemcitabine in patients with pancreatic cancer. The names of the study drugs involved in this study are:

• Adavosertib
• Gemcitabine

Conditions

Pancreatic Cancer

Keywords

Pancreatic Cancer

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  The primary objective is the evaluation of the overall response rate (ORR) by RECIST 1.1 criteria. Objective response rate (ORR) is defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

  Baseline and every 8 weeks during treatment until disease progression or unacceptable toxicity up to 2 years

Secondary Outcomes (4)

• Overall Survival (OS)

  Every 8 weeks during treatment, followed for survival after treatment discontinuation up to 2 years

• Progression-free Survival (PFS)

  Every 8 weeks during treatment, followed for survival after treatment discontinuation up to 2 years.

• Disease Control Rate (DCR)

  Baseline and every 8 weeks during treatment until disease progression or unacceptable toxicity up to 2 years

• Incidence of Grade 3 or Higher Treatment-Related Toxicity

  Assessed day 1, 2, 3, 8, 9, 10, 15 and 22 at cycle 1, also day 1, 8, 9 and 15 at cycle 2+, and off-treatment up to 2 years. Each cycle is 28 days.

Study Arms (1)

Adavosertib and Gemcitabine

EXPERIMENTAL

Participants will receive: * Adavosertib 1x per day on days 2, 3, 9, 10, 16, and 17 of every 28 day study cycle. * Gemcitabineon on days 1,8, and 15 of every 28-day cycle

Drug: Adavosertib; Drug: Gemcitabine

Interventions

Adavosertib DRUG

Taken Orally

Also known as: AZD 1775

Adavosertib and Gemcitabine

Gemcitabine DRUG

Intravenous Infusion

Also known as: Gemzar

Adavosertib and Gemcitabine

Eligibility Criteria

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

You may qualify if:

• Participants must have a histologically confirmed advanced pancreatic adenocarcinoma that is not curable with standard approaches based on the judgement of the treating investigator. Patients with metastatic pancreatic cancer and unresectable pancreatic cancer are eligible.
• Patients must have progressed on a platinum-based regimen prior to enrolling on the trial.
• Patients must have received no more than 1 prior lines of platinum-based chemotherapy in the metastatic setting. Therapy given in the adjuvant or neoadjuvant setting is counted as a prior therapy if it occurred less than 6 months before cancer recurrence or progression.
• Age ≥ 18 years. As no dosing or adverse event data are currently available in participants \< 18 years of age, children and adolescents are excluded from this study.
• ECOG performance status of 0 or 1 (see Appendix A).
• Participants must have adequate organ and marrow function as defined below:
• Absolute neutrophil count ≥ 1,500/mm3
• Platelets ≥ 100,000/mm3
• Hemoglobin ≥ 9 g/dL
• Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN); or total bilirubin ≤3.0 x ULN with direct bilirubin WNL in patients with documented Gilbert's Syndrome.
• Alanine aminotransferase (ALT) and ≤ 3 × institutional ULN; or ≤ 5 × institutional aspartate aminotransferase (AST) ULN if known hepatic metastases
• Albumin ≥ 2.7 g/dL
• Serum creatinine ≤ 1.5 × institutional ULN -OR-
• Creatinine clearance measured creatinine clearance (CrCl) ≥50 mL/min as calculated by either the Cockcroft-Gault method, a 24-hour urine test or another validated test as per local practice (confirmation of creatinine clearance is only required when creatinine is \>1.5 x institutional ULN)
• Cockcroft-Gault equation for estimated CrCL:

You may not qualify if:

• \- Patients who have previously received adavosertib are not eligible.
• \- Use of an anti-cancer treatment drug ≤ 21 days or 5 half-lives (whichever is shorter) prior to the first dose of adavosertib (AZD1775).
• \- Any prior palliative radiation must have been completed at least 7 days prior to the first dose of adavosertib, and patient must have recovered from any acute adverse effects, that the treating investigator thinks could impair the tolerance of the study drugs, prior to the start of study treatment.
• \- Participants who have undergone major surgical procedures ≤ 28 days, or minor surgical procedures ≤ 7 days, of the first dose of adavosertib. No waiting period is required following port-a-cath or other central venous access placement.
• \- Presence of CTCAE v5.0 Grade \>1 toxicity from prior therapy (except alopecia, anorexia or CTCAE grade 2 peripheral neuropathy).
• \- Patient is unable to swallow oral medications. Note: Patient may not have a percutaneous endoscopic gastrostomy (PEG) tube or be receiving total parenteral nutrition (TPN).
• \- Participants with known malignant central nervous system (CNS) disease other than neurologically stable, treated brain metastases - defined as metastasis having no evidence of progression or hemorrhage for at least 2 weeks after the completion of treatment (including brain radiotherapy). Must be off any systemic corticosteroids for the treatment of brain metastases for at least 14 days prior to enrollment.
• \- Participants receiving any medications or substances that are known to be moderate to strong inhibitors or inducers of CYP3A4 and which cannot be discontinued at least 2 weeks prior to the first dose of adavosertib are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the participant will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participant is considering a new over-the-counter medicine or herbal product. Refer to Protocol Section 5 for information on prohibited concomitant medications.
• \- Use of herbal medications or supplements within 7 days prior to the first dose of adavosertib.
• \- History of hypersensitivity to compounds of similar chemical or biologic composition to gemcitabine or adavosertib.
• \- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or psychiatric illness/social situations that would limit compliance with study requirements.
• \- Known HIV-positive participants are ineligible because these participants are at increased risk of lethal infections when treated with marrow-suppressive therapy.
• \- Participants with a clinically significant gastrointestinal disorder that in the opinion of the treating investigator could impact the absorption of the study drugs, including but not limited to refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of adavosertib.
• \- Participants with a history of a clinically relevant second primary malignancy within the past 2 years. Exceptions include: resected basal and squamous cell carcinomas of the skin and completely resected carcinoma in situ of any type.
• \- Pregnant or lactating women are excluded from this study because gemcitabine/adavosertib are anti-cancer agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with gemcitabine/adavosertib, breastfeeding should be discontinued if the mother is treated with gemcitabine/adavosertib.

Sponsors & Collaborators

• James Cleary, MD, PhD: lead
• AstraZeneca: collaborator
• Lustgarten Foundation: collaborator
• Stand Up To Cancer: collaborator

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

adavosertib; Gemcitabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• James Cleary, MD, PhD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 6, 2022
• First Posted: January 27, 2022
• Study Start: June 1, 2022
• Primary Completion: June 1, 2023
• Study Completion: December 31, 2023
• Last Updated: June 14, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu