OLAParib COmbinations

NCT02576444 | Terminated Phase 2 Results DMC

• 1 other identifier: 1508016363
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 4

Brief Summary

The primary objective of this phase II trial is to determine tumor overall response rate (ORR) in molecularly selected patients with measurable disease as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST), before versus after 16 weeks of treatment across tumor types in each arm of the study.

Conditions

Cancer

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  Tumor overall response rate (ORR) in molecularly selected patients with measurable disease as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST), before versus after 16 weeks of treatment across tumor types in each arm of the study (Note: there will be no formal comparison between arms). Complete Response (CR): disappearance of all target lesions, Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease (PD). Clinical Benefit is defined as the sum of CR, PR, or SD at 16 weeks from the start of treatment.

  Change from baseline to 16 weeks

Study Arms (4)

Group 1

EXPERIMENTAL

Patients with cholangiocarcinoma harboring IDH 1/2 tumors will be treated with olaparib. Patients with tumors harboring mutation in HDR genes will be treated with olaparib.

Drug: AZD2281

Group 2

EXPERIMENTAL

Patients with tumors harboring PTEN, PIK3CA, AKT, or ARID1A mutations or other molecular aberrations leading to dysregulation of the PI3K/AKT pathway will be treated with AZD5363 plus olaparib.

Drug: AZD2281; Drug: AZD5363

Group 3

EXPERIMENTAL

Patients with tumors harboring either TP53 or KRAS mutations or mutations in KRAS and TP53 will be treated with AZD1775 plus olaparib. TP53 mutations must be found on the TP53 mutation eligibility list.

Drug: AZD2281; Drug: AZD1775

Group 4

EXPERIMENTAL

Patients with tumors harboring mutations in HDR genes, including ATM, CHK2, APOBEC, MRE11 complex, will be treated with AZD6738 and olaparib.

Drug: AZD2281; Drug: AZD6738

Interventions

AZD2281 DRUG

Patients will be administered olaparib orally twice daily (bid) at 300 mg. Two (2) x 150 mg olaparib tablets should be taken at the same times each morning and evening of each day, approximately 12 hours apart with approximately 240 mL of water.

Also known as: Olaparib

Group 1; Group 2; Group 3; Group 4

AZD5363 DRUG

Patients will be administered AZD5363 at 640 mg twice daily for two days on/five days off (2/7) schedule. Two (2) 200 mg tablets and three (3) 80 mg tablets should be taken twice daily.

Group 2

AZD1775 DRUG

The recommended dose will be available no earlier than March 2016.

Group 3

AZD6738 DRUG

Patients will be administered AZD6738 at 160 mg daily for days 1-7 of a 28-day cycle (7/28) schedule. AZD6738 is available as 100, 20, and 10 mg tablets. Tablets should be taken daily.

Group 4

Eligibility Criteria

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

You may qualify if:

• Histologically documented metastatic cancer (solid tumors, not including hematologic malignancies)
• Patients who have received standard first-line therapy for metastatic cancer (except for the tumors for which no first-line therapy exists) and in whom a trial of targeted therapy is considered the best available treatment option. Eligible patients should not have available therapies that will convey clinical benefit.
• Progressive cancer at the time of study entry
• Measurable disease by RECIST v1.1
• Age ≥ 18 years
• Life expectancy ≥ 16 weeks
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1 (APPENDIX A: Performance Status Criteria)
• Able to understand the nature of this trial and provide written informed consent
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
• Molecular testing or appropriate IHC results from CLIA-certified laboratories used for patient eligibility should be obtained from the most recent tumor biopsy (baseline tumor biopsies and on-progression tumor biopsies are optional)
• No previous treatment with olaparib or any other drug sharing the same target. Prior treatment with PARP inhibitor monotherapy is allowed in the combination arms.
• Prior radiation therapy is allowed. Patients must not have received radiation therapy within 21 days prior to the initiation of study treatment.
• Other therapies: Prior experimental (non-FDA approved) therapies and immunotherapies are allowed. Patients must not have received these therapies for 21 days or five half-lives of the drug (whichever is less) prior to the initiation of study treatment and must have full recovery from any acute clinically significant effects of these therapies.
• Adequate hematologic function defined as:
• Absolute neutrophil count (ANC) ≥ 1500/μL

You may not qualify if:

• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
• Prior standard of care cancer chemotherapy, immunotherapy, or radiotherapy \<21 days prior to first dose of study agent(s)
• Patients with hematologic malignancies (includes patients with myelodysplastic syndrome/acute myeloid leukemia).
• Patients with primary CNS malignancies
• Patients must not have received allogeneic stem cell transplant
• Concurrent administration of any other anti-cancer therapy
• Bisphosphonates and Denosumab for bone metastases are allowed if started at least 4 weeks prior to treatment with study agent(s).
• Octreotide is allowed if dose is stable for \>3 months with no worsening of carcinoid syndrome
• Hormonal therapy with luteinizing hormone-releasing hormone (LHRH) analogues for medical castration in patients with castrate-resistant prostate cancer is permitted
• Patients who have not demonstrated stable recover (28 days or greater) from ≤ CTCAE grade 2 non-hematological toxicities related to prior therapy such as peripheral neuropathy or alopecia, or incomplete recovery from previous surgery, unless agreed by the Principal Investigator (PI) and documented are not eligible to participate in this study.
• Active or untreated brain metastases or spinal cord compression
• A scan to confirm the absence of brain metastases is not required.
• Patients with treated brain metastases or spinal cord compression are eligible if they have minimal neurologic symptoms and evidence of stable disease (for at least 1 month) or response on follow-up scan. The patient can receive a stable dose of corticosteroids before and during the study if started at least 28 days prior to initiating the study agent(s)..
• History of carcinomatous meningitis
• Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated stage I cancers (cervix, breast, colon, lung, or prostate as examples) or other advanced (\> Stage I)solid tumors curatively treated with no evidence of disease for ≥ 5 years.

Sponsors & Collaborators

• Joseph Paul Eder: lead
• Dana-Farber Cancer Institute: collaborator
• Vanderbilt-Ingram Cancer Center: collaborator
• The Cleveland Clinic: collaborator

Study Sites (4)

Yale Cancer Center

New Haven, Connecticut, 06520-8028, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Cleveland Clinic Taussig Cancer Institute

Cleveland, Ohio, 44195, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Neoplasms

Interventions

olaparib; capivasertib; adavosertib; ceralasertib

Results Point of Contact

• Title: Joseph Paul Eder, MD
• Organization: Yale School of Medicine: Medical Oncology

joseph.eder@yale.edu

(203) 737-6980

Study Officials

• Joseph P Eder, MD

  Yale University Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine; Clinical Director, Early Drug Development Program

Study Record Dates

• First Submitted: October 12, 2015
• First Posted: October 15, 2015
• Study Start: November 1, 2015
• Primary Completion: November 18, 2019
• Study Completion: November 18, 2019
• Last Updated: December 28, 2022
• Results First Posted: December 28, 2022

Record last verified: 2022-11

Locations

US (4)