A Dose-Ranging Study of IPH2201 in Patients With Gynecologic Malignancies

NCT02459301 | Completed Phase 1 DMC

• 1 other identifier: I221
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this study is to test the safety of a new drug, IPH2201, to see what effects it has on this type of cancer.

Conditions

Gynecologic Cancer

Outcome Measures

Primary Outcomes (1)

• Dose of single agent IPH2201 for phase II studies and determined based on toxicity, as well as pharmacokinetic and pharmacodynamics data

  To confirm the recommended phase II dose (RP2D) of single agent IPH2201 in patients with advanced/metastatic/recurrent platinum sensitive or resistant high-grade serous carcinoma (HGSC) of ovarian, fallopian tube or peritoneal origin.

  24 months

Secondary Outcomes (4)

• Number and severity of adverse events in patients

  24 months

• Correlative assays evaluation for potential predictive markers of IPH2201 effects. Concentration at the end of administration (Cinf end) for all patients

  24 months

• Area under the curve from time 0 to Tau=2 weeks (AUC(0-Tau)

  24 months

• Accumulation ratio, in terms of Cmax and AUC(0-Tau), between C1 and C4

  24 months

Study Arms (1)

IPH2201

EXPERIMENTAL

Part 1: 1, 4 or 10mg/kg, IV, 1 hour duration on Day 1 every 2 weeks. Part 2: Patients will receive single agent IPH2201 as above with the actual dose dependent on the outcome of Part 1

Drug: IPH2201

Interventions

IPH2201 DRUG

IPH2201

Eligibility Criteria

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

You may qualify if:

• Patients must have a histologically and/or cytologically confirmed gynecologic malignancy including high-grade serous ovarian/fallopian tube or peritoneal carcinoma, cervical cancer (squamous cell carcinoma) or endometrial cancer (adenocarcinoma), that is advanced/metastatic/recurrent or unresectable and for which no curative therapy exists.
• For patients with HGSC: For Part 2 of this study, patients will be classified as either platinum resistant or platinum sensitive, as defined by their previous response to platinum-based therapy:
• The platinum resistant cohort will include patients with disease progression within 6 months of the last line of platinum-based therapy dose.
• The platinum sensitive cohort will be defined by progression 6 months or longer since last platinum-based therapy dose.
• All patients must have an available formalin fixed paraffin embedded tissue block (from their primary or metastatic tumour) and must have provided informed consent for the release of the block (or slides), as well as for samples for correlative studies and banking.
• At least 4 patients registered to each cohort in Part 2 must also have provided informed consent for and be willing to undergo a tumour biopsy prior to treatment (after registration) and after treatment with IPH2201. Note: During accrual to Part 2, it may be necessary to restrict accrual to patients who are suitable for, and have consented to, tumour biopsy before and after treatment.
• Presence of clinically and/or radiologically documented disease. All radiology studies must be performed within 28 days prior to randomization/registration (within 35 days if negative).
• All patients must have measurable disease as defined by RECIST 1.1. The criteria for defining measurable disease are as follows:
• Chest x-ray ≥ 20 mm CT scan (with slice thickness of 5 mm) ≥ 10 mm --\> longest diameter Physical exam (using calipers) ≥ 10 mm Lymph nodes by CT scan ≥ 15 mm --\> measured in short axis
• Patients must be ≥ 18 years of age.
• Patients must have an ECOG performance status of 0, 1, or 2.
• Previous Therapy
• Cytotoxic Chemotherapy: All patients must have received at least one prior regimen of chemotherapy for advanced, metastatic, or recurrent disease, one of which must have been platinum-based. Patients may have received no more than 3 prior regimens.
• Other systemic therapy: All patients may have received other therapies including immunotherapy, angiogenesis inhibitors, PARP inhibitors or signal transduction inhibitors.
• Patients must have recovered from all reversible toxicity related to prior chemotherapy or systemic therapy and have adequate washout as follows:

You may not qualify if:

• Patients with a history of other active or current malignancies that require active treatment.
• Patients with serious illness or medical conditions that might be aggravated by treatment or limit compliance including, but not limited to:
• History of significant neurologic or psychiatric disorder which would impair the ability to obtain consent or limit compliance with study requirements.
• Uncontrolled diabetes
• Active uncontrolled or serious infection (viral, bacterial or fungal)
• Other medical conditions that might be aggravated by study treatment
• Patients with active immune-mediated diseases or known HIV infection or hepatitis B or C.
• Patients receiving systemic corticosteroid therapy at doses equivalent to more than 5 mg prednisone. Note: Topical applications (e.g. rash), inhaled sprays (e.g. obstructive airways diseases), eye drops or local injections (e.g. intra-articular) are permitted.
• Patients receiving cytokines and/or growth factors.
• Patients who have experienced severe adverse effects from other immunotherapy-based treatment or monoclonal antibodies.
• Patients receiving concurrent treatment with other anti-cancer therapy or investigational agents.

Sponsors & Collaborators

• Canadian Cancer Trials Group: lead
• Innate Pharma: collaborator

Study Sites (7)

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

BCCA - Cancer Centre for the Southern Interior

Kelowna, British Columbia, V1Y 5L3, Canada

Location

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

London Regional Cancer Program

London, Ontario, N6A 5W9, Canada

Location

University Health Network

Toronto, Ontario, M5G 2M9, Canada

Location

CHUM - Hopital Notre-Dame

Montreal, Quebec, H2L 4M1, Canada

Location

Related Publications (2)

• Tinker AV, Hirte HW, Provencher D, Butler M, Ritter H, Tu D, Azim HA Jr, Paralejas P, Grenier N, Hahn SA, Ramsahai J, Seymour L. Dose-Ranging and Cohort-Expansion Study of Monalizumab (IPH2201) in Patients with Advanced Gynecologic Malignancies: A Trial of the Canadian Cancer Trials Group (CCTG): IND221. Clin Cancer Res. 2019 Oct 15;25(20):6052-6060. doi: 10.1158/1078-0432.CCR-19-0298. Epub 2019 Jul 15.

  PMID: 31308062 RESULT

• Roberto A, Di Vito C, Zaghi E, Mazza EMC, Capucetti A, Calvi M, Tentorio P, Zanon V, Sarina B, Mariotti J, Bramanti S, Tenedini E, Tagliafico E, Bicciato S, Santoro A, Roederer M, Marcenaro E, Castagna L, Lugli E, Mavilio D. The early expansion of anergic NKG2Apos/CD56dim/CD16neg natural killer represents a therapeutic target in haploidentical hematopoietic stem cell transplantation. Haematologica. 2018 Aug;103(8):1390-1402. doi: 10.3324/haematol.2017.186619. Epub 2018 Apr 26.

  PMID: 29700172 DERIVED

Study Officials

• Hal Hirte

  Juravinski Cancer Centre at Hamilton Health Sciences, ON Canada

  STUDY CHAIR

• Anna Tinker

  BCCA - Vancouver Cancer Centre, BC Canada

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: May 19, 2015
• First Posted: June 2, 2015
• Study Start: September 17, 2015
• Primary Completion: November 15, 2017
• Study Completion: November 12, 2019
• Last Updated: August 4, 2023

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (7)