AZD2281 and Irinotecan in Treating Patients With Locally Advanced or Metastatic Colorectal Cancer

NCT00535353 | Completed Phase 1 DMC

• 4 other identifiers: I187CAN-NCIC-IND187IND187CDR0000565189
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 2

Brief Summary

RATIONALE: AZD2281 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving AZD2281 together with irinotecan may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of AZD2281 and irinotecan in treating patients with locally advanced or metastatic colorectal cancer.

Conditions

Colorectal Cancer

Keywords

recurrent colon cancer; stage IV colon cancer; recurrent rectal cancer; stage IV rectal cancer; stage III rectal cancer; stage III colon cancer

Outcome Measures

Primary Outcomes (6)

• Recommended phase II dose of AZD2281 and irinotecan hydrochloride

  End of study

  Nov 2011

• Safety

  End of study

  Nov 2011

• Tolerability

  End of study

  Nov 2011

• Dose-limiting toxicities

  Fatigue, Nausea, Dehydration and Anorexia.

  2011-May-28

• Pharmacokinetic profile

  End of study

  Nov 2011

• Correlation, if any, between the toxicity profile and pharmacokinetics

  End of study.

  Nov 2011

Secondary Outcomes (2)

• Efficacy

  Nov 2011

• Pharmacodynamic outcomes

  Nov 2011

Interventions

irinotecan hydrochloride DRUG

In Part A, a continuous oral AZD2281 dose will be given in combination with irinotecan given as a 90 minute infusion on day 1 every 21 days. In Part B, AZD2281 will be given on days 1-5 and irinotecan as a 90 minute infusion on day 3 each cycle. Cycles are repeated every 14 days.

olaparib DRUG

In Part A, a continuous oral AZD2281 dose will be given in combination with irinotecan given as a 90 minute infusion on day 1 every 21 days. In Part B, AZD2281 will be given on days 1-5 and irinotecan as a 90 minute infusion on day 3 each cycle. Cycles are repeated every 14 days.

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed colorectal cancer * Locally advanced and/or metastatic disease * Disease considered incurable * Suitable for treatment with single agent irinotecan hydrochloride as a palliative intervention, as determined by the investigator * Must have clinically and/or radiologically documented disease * Patients whose only evidence of disease progression is tumor marker elevation are not eligible * Must have received no more than one prior oxaliplatin- and/or irinotecan hydrochloride-based chemotherapy regimen given either with adjuvant, neoadjuvant, or palliative intent * One additional adjuvant fluoropyrimidine (fluorouracil or capecitabine) regimen may have been given for relapsed or metastatic disease * No untreated brain or meningeal metastases (CT scan required if there is a clinical suspicion of CNS disease) PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * Absolute granulocyte count ≥ 1,500/mm³ * Platelet count ≥ 100,000/mm³ * Bilirubin ≤ 1.5 times upper limit of normal (ULN) * ALT and AST ≤ 2 times ULN (≤ 5 times ULN if liver metastasis is present) * Serum creatinine ≤ 1.5 x ULN OR creatinine clearance ≥ 50 mL/min * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 90 days after completion of study therapy * Must reside within a 1½ hour drive from participating center * No other invasive malignancies, unless curatively treated with no evidence of disease * No GI tract disease resulting in an inability to absorb oral medication, including the following: * Uncontrolled inflammatory GI disease (e.g., Crohn's disease or ulcerative colitis) * Post-surgical malabsorption characterized by uncontrolled diarrhea that results in weight loss and vitamin deficiency or requires IV hyperalimentation * Pancreatic enzyme supplementation is allowed * No untreated and/or uncontrolled hypertension, cardiovascular conditions, and/or symptomatic cardiac dysfunction * No active or uncontrolled infections * No serious illnesses or medical conditions that would preclude study participation * No known hypersensitivity to the study drugs or their components, atropine, or loperamide * Not known to be homozygous for the UGT1A1\*28 allele * No known deficiency in glucuronidation of bilirubin, such as Gilbert's syndrome * No neuropathy ≥ grade 2 * Patients with persistent, stable, grade 3 sensory neuropathy, who meet other eligibility criteria may be allowed at the discretion of the investigator PRIOR CONCURRENT THERAPY: * Recovered from all prior therapy * No prior PARP inhibitor * No prior radical pelvic irradiation * No prior radiotherapy to ≥ 25% of bone marrow stores * Prior irinotecan hydrochloride allowed provided the drug was not discontinued due to toxic effects and the patient did not have severe irinotecan hydrochloride-related toxicity (grade 4 or requiring hospitalization) * At least 21 days since prior radiotherapy (exceptions may be made for low-dose, nonmyelosuppressive radiotherapy) * At least 30 days since prior chemotherapy * At least 21 days since prior hormonal, immunologic, biologic, or signal transduction inhibitor therapies * More than 3 weeks since prior and no other concurrent investigational drugs or anticancer therapy * At least 14 days since prior major surgery * Wound healing must have occurred * At least 14 days since prior and no concurrent CYP3A4 enzyme-inducing or -inhibiting drugs, including enzyme-inducing anticonvulsants, rifampin, rifabutin, St. John's wort, atazanavir, or ketoconazole * Dexamethasone is allowed for antiemetic prophylaxis

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• NCIC Clinical Trials Group: lead
• AstraZeneca: collaborator

Study Sites (2)

Ottawa Health Research Institute - General Division

Ottawa, Ontario, K1H 8L6, Canada

Location

Univ. Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Related Publications (1)

• Chen EX, Jonker DJ, Siu LL, McKeever K, Keller D, Wells J, Hagerman L, Seymour L. A Phase I study of olaparib and irinotecan in patients with colorectal cancer: Canadian Cancer Trials Group IND 187. Invest New Drugs. 2016 Aug;34(4):450-7. doi: 10.1007/s10637-016-0351-x. Epub 2016 Apr 13.

  PMID: 27075016 RESULT

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms; Rectal Neoplasms

Interventions

Irinotecan; olaparib

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• Eric X. Chen, MD, PhD

  Princess Margaret Hospital, Canada

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 25, 2007
• First Posted: September 26, 2007
• Study Start: January 2, 2008
• Primary Completion: September 25, 2012
• Study Completion: February 13, 2015
• Last Updated: August 4, 2023

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2)